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11-1470550-000001-14

Instrumental Analysis Data of Illegal


Compounds in Food

(2008 Norneovardenafil )

1. Mirodenafil 1
2. Sildenafil 6
3. Tadalafil 11
4. Udenafil 16
5. Vardenafil 21


1. Aminotadalafil 26
2. epi-Aminotadalafil 31
3. Benzylsildenafil 36
4. Demethylhongdenafil 42
5. Dimethylsildenafil 48
6. Homosildenafil 54
7. Hongdenafil 59
8. Hydroxyhomosildenafil 64
9. Hydroxyhongdenafil 69
10. Hydroxyvardenafil 75
11. Norneosildenafil 81

- i -

12. Piperidinohongdenafil 87
13. Pseudovardenafil 93
14. Thiosildenafil 98
15. Xanthoanthrafil 104

1. Desmethylsibutramin 109
2. N-Nitrosofenfluramin 114

- ii -

Mirodenafil

// : Mirodenafil / SK3530 / Mvix
/ : C26H37N5O5S / 531.67
: 5-Ethyl-3,5-dihydro-2-[5-[[4-(2-hydroxyethyl)-1-piperazinyl]sulfonyl]-2-propoxyphenyl]-7-propyl-4H-pyrrolo[3,2-d]pyrimidin-4-one
O

HN

S
N

N
N
HO


HPLC RT (min) : 21.84
UV max (nm) : 210.9, 252.6
IR (cm-1) : (CHCl3). 3365(m), 2965(m), 1710(s), 1636(m),
1459(w), 1352(w), 1284(w), 1168(m), 1090(w), 940(w), 752(w)

- 1 -

Mass (m/z) : FAB+ (m-NBA). 532([M-2HCl+H]+, 17%), 500(1%),


431(3%), 404(2%)
1

H NMR (400 MHz, DMSO-d6) : 0.92(3H, t, J = 7.1 Hz, H-14),


0.93(3H, t, J = 7.1 Hz, H-23), 1.37(3H, t, J = 7.1 Hz, H-11), 1.61(2H,
m, H-13), 1.73(2H, m, H-22), 2.62(2H, t, J = 7.5 Hz, H-12), 2.94(2H,
t, J = 11.8 Hz, H-31), 3.18(4H, br m, H-27,29), 2.97(4H, br m,
H-26,30), 2.77(2H, t, J = 7.5 Hz, H-32), 4.15(2H, t, J = 6.3 Hz,
H-21), 4.39(2H, q, J = 7.1 Hz, H-10), 7.46(1H, d, J = 8.8 Hz, H-19),
7.47(1H, s, H-2), 7.93(1H, dd, J = 8.8, 1.9 Hz, H-18), 8.06(1H, d, J =
1.9 Hz, H-16), 11.00(1H, br s, NH)

13

C NMR (100 MHz, DMSO-d6) : 10.3(C-23), 13.8(C-14), 17.3(C-11),

21.7(C-22), 23.2(C-13), 25.3(C-12), 42.7(C-31), 43.0(C-10),


50.6(C-26,30), 55.1(C-27,29), 57.6(C-32), 70.7(C-21), 113.7(C-19),
114.8(C-9), 115.1(C-1), 126.5(C-15), 130.0(C-2), 130.8(C-16),
132.1(C-18), 147.9(C-6), 153.1(C-4), 160.4(C-20)
HPLC Chromatogram of Mirodenafil

- 2 -

UV Spectrum of Mirodenafil

IR spectrum of Mirodenafil

- 3 -

Mass spectrum of Mirodenafil (FAB+)

[M-2HCl+H]+

Theoretical Ion Distribution of Mirodenafil (FAB+)


Molecular Formula : C26 H38 N5 O5 S
(m/z 532.2594, MW 532.6842, U.S. 11.5)
Base Peak : 532.2594, Averaged MW : 532.6846 (a), 532.6856 (w)
m/z
532.2594
533.2623
534.2608
535.2617
536.2628
537.2643
538.2659
539.2676

INT.
100.0000
32.3047
10.4836
2.2288
0.3699
0.0500
0.0057
0.0006

**********************************************************

*******************
******
*

Elemental Composition of Mirodenafil (FAB+)


Observed m/z
532.2590

Int%
90.8

Err[ppm
-3.1
+4.4
-0.6
+6.9
+1.9
-9.1
+9.1
-4.4
+3.1

/
/
/
/
/
/
/
/
/

mmu]
-1.7
+2.3
-0.3
+3.7
+1.0
-4.9
+4.8
-2.4
+1.7

- 4 -

Unsaturation
11.0
7.0
11.5
7.5
12.0
3.0
12.0
8.0
4.0

Composition
C 28 H 40 O
C 23 H 40 O
C 26 H 38 O
C 21 H 38 O
C 24 H 36 O
C 17 H 40 O
C 27 H 40 O
C 21 H 40 O
C 16 H 40 O

6
8
5
7
4
9
3
4
6

N
N
N
N
N
N
N
N
N

2S
4S
5S
7S
8S
8S
4S2
8S2
10 S 2

1H-NMR

spectrum of Mirodenafil (400MHz, DMSO)

32
31

15

HO

16

27

18

30

HN

26

11

23 14

2
8

1
12

21

19

29

11

10

22

13

14

23

21
19
2

16

32
27
29

12

10
26
30

18

22

13

31

13C-NMR

spectrum of Mirodenafil (100MHz, DMSO)

4
26
32
HO

16

27

31

30

15

18

19

29

HN

11

10

O
N

2
8

1
12

21
22

23

13

14

14 23
13

20

1
15

4
6

31
9
19

21

16
18 2

- 5 -

32

27
29

26
30
10

12

11
22

Sildenafil

/ : Sildenafil / Viagra
/ : C22H30N6O4S / 474.59
:

1-[[3-(4,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo
[4,3-d]

pyrimidine-5-yl)-4-ethoxyphenyl]sulfonyl]-4-

methylpierazine
O

HN

S
N

N
N
O


HPLC RT (min) : 14.5
UV max (nm) : 214.4, 295.9
-1

IR (cm ) : KBr. 3445(s), 1702(s), 1582(m), 1461(w), 1360(w),


1172(m), 940(w), 736(w)
+

Mass (m/z) : EI+ (70eV). 474([M] , 9%), 410(14%), 404(90%),


381(10%), 311(18%), 283(17%), 99(100%), 70(15%), 56(49%)

- 6 -

H NMR (400 MHz, DMSO-d6) : 0.93(3H, t, J = 7.3 Hz, H-13),

1.33(3H, t, J = 6.9 Hz, H-21), 1.73(2H, m, H-12), 2.29(3H, s, H-29),


2.59(4H, br m, H-25,27), 2.77(2H, t, J = 7.5 Hz, H-11), 2.97(4H, br
m, H-24,28), 4.16(3H, s, H-10), 4.21(2H, q, J = 6.9 Hz, H-20),
7.38(1H, d, J = 8.8 Hz, H-18), 7.84(1H, dd, J = 8.8, 2.4 Hz, H-17),
7.86(1H, d, J = 2.3 Hz, H-15), 12.23(1H, br s, NH)

13

C NMR (100 MHz, DMSO-d6) : 13.9(C-13), 14.3(C-21), 21.7(C-12),

27.2(C-11),

37.9(C-10),

64.9(C-20),

113.3(C-18),

130.0(C-15),

44.5(C-29),

131.6(C-17),

45.1(C-24,28),

123.8(C-16),
137.8(C-8),

124.4(C-9),

53.1(C-25,27),
126.1(C-14),

145.0(C-1),

153.8(C-4), 160.0(C-19)
Elemental Analysis (%) : 12.49(N), 49.79(C), 5.80(H), 4.82(S)
HPLC Chromatogram of Sildenafil

- 7 -

148.2(C-6),

UV Spectrum of Sildenafil

IR spectrum of Sildenafil

- 8 -

Mass spectrum of Sildenafil (EI+)

[M]+

Theoretical Ion Distribution of Sildenafil (EI+)


Molecular Formula : C22 H30 N6 O4 S
(m/z 474.2049, MW 474.5840, U.S. 12.0)
Base Peak : 474.2049, Averaged MW : 474.5840 (a), 474.5850 (w)
m/z
474.2049
475.2077
476.2056
477.2065
478.2075
479.2088
480.2104
481.2120

INT.
100.0000
28.0650
9.0275
1.7625
0.2685
0.0330
0.0034
0.0003

**********************************************************

****************
*****
*

Elemental Composition of Sildenafil (EI+)


Observed m/z
474.2050

Int%
100.0

Err[ppm
-2.6
-8.2
+0.3
-5.4
+8.7

/
/
/
/
/
/

mmu]
-1.2
-3.9
+0.1
-2.6
+4.1

- 9 -

Unsaturation
11.5
16.0
12.0
16.5
8.0

Composition
C 24 H 32 O
C 27 H 30 O
C 22 H 30 O
C 25 H 28 O
C 17 H 30 O

5N
2N
4N
N7
6N

3
4
6
S
8

S
S
S
S

1H-NMR

spectrum of Sildenafil (400MHz, DMSO)

10
10

4
24
N

29

15

25

14

17

28

18

27

HN

N
N2

20

29

1
11

21

12
21

13

15

25
11 27
24
28

20

18

17

13

12

13C-NMR

spectrum of Sildenafil (100MHz, DMSO)

10

4
24
N

29

15

25

HN

28

17
18

27

14

N
N2

20

1
11

21

12
13
13
12

25
27
14

19
4

15 9
8

17

16

20

18

- 10 -

21

29
24
28

10

11

Tadalafil

/ : Tadalafil / Cialis
/ : C22H19N3O4 / 389.40
: (6R,12aR)-6-(1,3-benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydro2-methylpyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione
O

N
N

N
H

O
O


HPLC RT (min) : 19.0
UV max (nm) : 285.0
IR (cm-1) : (CHCl3). 3305(w), 2908(w), 1661(s), 1490(w),
1428(w), 1323(w), 1239(w), 1037(w), 924(w), 747(w)
+

Mass (m/z) : EI+ (70eV). 389([M] , 100%), 317(12%), 289(22%),


268(30%), 262(73%), 233(30%), 204(54%), 169(31%), 115(8%)

- 11 -

H NMR (400 MHz, DMSO-d6) : 2.93(3H, s, H-18), 2.99(1H, dd, J


= 15.7, 11.9 Hz, H-16), 3.54(1H, dd, J = 15.8, 4.5 Hz, H-16'),
3.95(1H, d, J = 17.1 Hz, H-3), 4.18(1H, d, J = 17.1 Hz, H-3'),
4.40(1H, dd, J = 11.6, 4.2 Hz, H-17), 5.93(2H, s, H-25), 6.14(1H, s,
H-6), 6.79(2H, H-23,24), 6.88(1H, s, H-20), 7.00(1H, t, J = 7.3 Hz,
H-12), 7.06(1H, t, J = 7.5 Hz, H-11), 7.31(1H, d, J = 8.0 Hz, H-10),
7.55(1H, d, J = 7.7 Hz, H-13), 11.04(1H, br s, NH)

13

C NMR (100 MHz, DMSO-d6) : 23.1(C-16), 32.9(C-18), 51.5(C-3),

55.3(C-17), 55.5(C-6), 100.9(C-25), 104.7(C-15), 107.0(C-20),


108.0(C-23), 111.3(C-10), 118.1(C-13), 118.9(C-12), 119.3(C-24),
121.2(C-11), 125.7(C-14), 133.9(C-7), 136.2(C-19), 137.0(C-9),
146.1(C-22), 147.0(C-21), 166.6(C-4), 166.9(C-1)
Elemental Analysis (%) : 10.95(N), 68.09(C), 4.86(H), 0(S)
HPLC Chromatogram of Tadalafil

- 12 -

UV Spectrum of Tadalafil

IR spectrum of Tadalafil

- 13 -

Mass spectrum of Tadalafil (EI+)


[M]+

Theoretical Ion Distribution of Tadalafil (EI+)


Molecular Formula : C22 H19 N3 O4
(m/z 389.1376, MW 389.4106, U.S. 15.0)
Base Peak : 389.1376, Averaged MW : 389.4117 (a), 389.4125 (w)
m/z
389.1376
390.1407
391.1434
392.1460
393.1486
394.1511
395.1537

INT.
100.0000 **********************************************************
26.0086 ***************
4.0460 **
0.4666
0.0431
0.0033
0.0002

Elemental Composition of Tadalafil (EI+)


Observed m/z
389.1373

Int%
100.0

Err[ppm
+6.3
-0.6
-7.5
+9.8
+2.9
-12.2

/
/
/
/
/
/
/

mmu]
+2.5
-0.2
-2.9
+3.8
+1.1
-4.8

- 14 -

Unsaturation
10.5
15.0
19.5
11.0
15.5
6.5

Composition
C 19 H 21 O
C 22 H 19 O
C 25 H 17 O
C 17 H 19 O
C 20 H 17 O
C 13 H 21 O

7N
4N
N4
6N
3N
8N

2
3
5
6
6

1H-NMR

spectrum of Tadalafil (400MHz, DMSO)

12

13

14

11
10

8
N
H

16

15

17
N

24

20

25

18

19

23
24

18
N

21

23
22

20

25

3
10

8
13

12
11

16
17

13C-NMR

spectrum of Tadalafil (100MHz, DMSO)

12

13

14

11
10

15

N
H

16

17
N

19
24

20

22

O
O

18
N

21

23

18

25

21

24

22
9
19

12
11 13

23

20

25

15
10

6 17
3
16

14

- 15 -

Udenafil

/ : Udenafil / Zydena
/ : C25H36N6O4S / 516.67
: 3-(4,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d]pyrimidine-5-yl)-N-[2-(1-methyl-2-pyrrolidinyl)ethyl]-4propoxybenzenesulfonamide
O

HN

S
HN


HPLC RT (min) : 18.4
UV max (nm) : 213.5, 296.7
-1

IR (cm ) : (CHCl3). 3305(w), 2962(w), 1695(s), 1595(w),


1463(w), 1328(w), 1273(w), 1157(m), 754(w)
Mass (m/z) : EI+ (70eV). 516([M]+, 7%), 473(9%), 441(6%), 405(4%),
326(7%), 283(3%), 136(5%), 127(5%), 97(5%), 84(100%), 57(10%)
- 16 -

1H NMR (400 MHz, DMSO-d6) : 0.93(3H, t, J = 7.2 Hz, H-13),


0.95(3H, t, J = 7.2 Hz, H-22), 1.29(2H, m, H-26,31), 1.54(2H, m,
H-30), 1.73(6H, m, H-12,21,26,31), 1.97(2H, m, H-27,29), 2.11(3H, s,
H-32), 2.77(4H, t, J = 7.5 Hz, H-11,25), 2.86(1H, m, H-29), 4.09(2H,
t, J = 6.3 Hz, H-20), 4.16(3H, s, H-10), 7.34(1H, d, J = 8.8 Hz,
H-18), 7.87(1H, dd, J = 8.7, 2.4 Hz, H-17), 7.96(1H, d, J = 2.4 Hz,
H-15), 12.13(1H, br s, NH)

13

C NMR (100 MHz, DMSO-d6) : 10.4(C-22), 13.8(C-13), 21.6(C-30),

21.7, 21.8(C-12,21), 27.1(C-11), 29.7(C-31), 32.5(C-26), 37.9(C-10),


56.5(C-29), 63.1(C-27), 70.2(C-20), 113.1(C-18), 123.4(C-16),
124.3(C-9), 128.9(C-15), 130.4(C-17), 132.0(C-14), 137.8(C-8),
144.9(C-1), 148.4(C-6), 153.6(C-4), 159.3(C-19)
Elemental Analysis (%) : 16.47(N), 58.02(C), 7.08(H), 6.16(S)
HPLC Chromatogram of Udenafil

- 17 -

UV Spectrum of Udenafil

IR spectrum of Udenafil

- 18 -

Mass spectrum of Udenafil (EI+)

[M]+

Theoretical Ion Distribution of Udenafil (EI+)


Molecular Formula : C25 H36 N6 O4 S
(m/z 516.2519, MW 516.6646, U.S. 12.0)
Base Peak : 516.2519, Averaged MW : 516.6650 (a), 516.6660 (w)
m/z
516.2519
517.2547
518.2531
519.2539
520.2549
521.2563
522.2579
523.2596

INT.
100.0000
31.4917
10.0293
2.0833
0.3326
0.0430
0.0046
0.0004

**********************************************************

******************
******
*

Elemental Composition of Udenafil (EI+)


Observed m/z
516.2521

Int%
100.0

Err[ppm
-2.1
-7.3
+0.5
-4.7
+8.3
+7.9
-6.0
+1.8

/
/
/
/
/
/
/
/
/

mmu]
-1.1
-3.8
+0.3
-2.4
+4.3
+4.1
-3.1
+0.9

- 19 -

Unsaturation
11.5
16.0
12.0
16.5
8.0
12.0
8.0
4.0

Composition
C 27 H 38 O
C 30 H 36 O
C 25 H 36 O
C 28 H 34 O
C 20 H 36 O
C 28 H 40 O
C 22 H 40 O
C 17 H 40 O

5N
2N
4N
N7
6N
3N
4N
6N

3
4
6
S
8
2
6
8

S
S
S
S
S2
S2
S2

1H-NMR

spectrum of Udenafil (400MHz, DMSO)

10

4
HN

15

S
HN 24

26

27

32

12
13

23

30

29

22 13

11

22

31

32

21

18

10

N
N

14

17

25

20

15

12
21
26?
31

11
25

27
29

18
17

13C-NMR

30 26
31

29

24

spectrum of Udenafil (100MHz, DMSO)

10

4
15

S
HN 24

26

25

17
18

27

32

29

N
N

14

21
22

31

HN

1
11

25
32

12
13

23

12
21
30

30

27
29

31
10
26

19
1
4

15 9
16
17
8 14

20

18

- 20 -

11

22
13

Vardenafil

/ : Vardenafil / Levitra
/ : C23H32N6O4S / 488.62
: 1-[[3-(1,4-dihydro-5-methyl-4-oxo-7-propylimidazo[5,1-f][1,2,4]triazin-2-yl)-4-ethoxyphenyl]sulfonyl]-4-ethylpiperazine
O

HN

N
O


HPLC RT (min) : 6.1
UV max (nm) : 218.1
-1

IR (cm ) : (CHCl3). 3398(w), 2966(w), 1697(s), 1626(w),


1470(w), 1355(w), 1283(w), 1162(m), 942(w), 753(w)
Mass (m/z) : EI+ (70eV). 488([M]+, 58%), 473(14%), 311(15%),
283(13%), 113(100%), 98(24%), 84(18%), 70(57%), 56(52%)
- 21 -

H NMR (400 MHz, DMSO-d6) : 0.94(3H, t, J = 7.4 Hz, H-13),


1.23(3H, t, J = 7.2 Hz, H-30), 1.35(3H, t, J = 6.9 Hz, H-21), 1.76(2H,
m, H-12), 2.50(3H, s, H-10), 2.86(2H, t, J = 7.4 Hz, H-11), 2.90(2H,
br m, H-29), 3.10(4H, br m, H-25,27), 3.50(2H, br m, H-24,28),
3.81(2H, br m, H-24,28), 4.24(2H, q, J = 6.9 Hz, H-20), 7.45(1H,
H-18), 7.95(2H, m, H-15,17), 11.82(1H, br s, NH)

13

C NMR (100 MHz, DMSO-d6) : 8.7(C-30), 13.7(C-21), 14.1(C-10),

14.3(C-13), 20.2(C-12), 27.1(C-11), 43.0(C-24,28), 49.4(C-25,27),


50.6(C-29), 65.1(C-20), 113.6(C-18), 113.7(C-9),

120.9(C-16),

126.4(C-14), 130.3(C-15), 132.2(C-17), 137.6(C-3), 144.4(C-1),


146.1(C-6), 155.0(C-4), 160.7(C-19)
HPLC Chromatogram of Vardenafil

- 22 -

UV Spectrum of Vardenafil

IR spectrum of Vardenafil

- 23 -

Mass spectrum of Vardenafil (EI+)

[M]+

Theoretical Ion Distribution of Vardenafil (EI+)


Molecular Formula : C23 H32 N6 O4 S
(m/z 488.2206, MW 488.6109, U.S. 12.0)
Base Peak : 488.2206, Averaged MW : 488.6110 (a), 488.6120 (w)
m/z
488.2206
489.2234
490.2214
491.2223
492.2233
493.2247
494.2262
495.2279

INT.
100.0000
29.2072
9.3484
1.8657
0.2887
0.0361
0.0038
0.0003

**********************************************************

*****************
*****
*

Elemental Composition of Vardenafil (EI+)


Observed m/z
488.2200

Int%
100.0

Err[ppm
-3.9
-9.4
-1.1
-6.6
+7.1

/
/
/
/
/
/

mmu]
-1.9
-4.6
-0.5
-3.2
+3.5

- 24 -

Unsaturation
11.5
16.0
12.0
16.5
8.0

Composition
C 25 H 34 O
C 28 H 32 O
C 23 H 32 O
C 26 H 30 O
C 18 H 32 O

5N
2N
4N
N7
6N

3
4
6
S
8

S
S
S
S

1H-NMR

spectrum of Vardenafil (400MHz, DMSO)

10

25
30

15

S
N

29

HN

24

18

27

10

21

13

14

17

28

20

11
21

12

30

11,29

13

15 17
20

12

18
5

25,27
24,28

13C-NMR

spectrum of Vardenafil (100MHz, DMSO)

10

4
24
25
30

15

S
N

29

HN

28

14

17

18

27

20

11
21

12

21

13

10
12 13

11
18
9

19

1
4

20

15 14 16

29

25
27
24
28

17

30

- 25 -

Aminotadalafil

: Aminotadalafil
/ : C21H18N4O4 / 390.39
: 2-amino-6-(1,3-benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydro(6R,12aR)-pyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione
O
NH2
N
N

N
H

O
O


HPLC RT (min) : 15.3
UV max (nm) : 285.0
IR (cm-1) : KBr. 3436(s), 2896(w), 1655(s), 1499(w), 1415(w),
1320(w), 1240(m), 1038(w), 925(w), 739(w)
+

Mass (m/z) : EI+ (70eV). 390([M] , 100%), 375(11%), 318(11%),


289(32%), 269(12%), 262(49%), 233(19%), 204(47%), 169(26%)
- 26 -

1H NMR (400 MHz, DMSO-d6) : 3.00(1H, dd, J = 15.4, 11.9 Hz,


H-16), 3.58(1H, dd, J = 15.7, 4.2 Hz, H-16), 3.97(1H, d, J = 17.1
Hz, H-3), 4.27(1H, d, J = 17.2 Hz, H-3), 4.44(1H, dd, J = 11.6, 3.5
Hz, H-17), 5.13(2H, s, H-18), 5.93(2H, s, H-25), 6.10(1H, s, H-6),
6.78(1H, d, J = 8.0 Hz, H-23), 6.82(1H, dd, J = 8.2, 1.4 Hz, H-24),
6.88(1H, d, J = 1.2 Hz, H-20), 7.02(1H, t, J = 8.4 Hz, H-12), 7.06
(1H, t, J = 7.1 Hz, H-11), 7.30(1H, d, J = 7.9 Hz, H-10), 7.56(1H, d,

J = 7.7 Hz, H-13), 11.02(1H, br s, NH)

13

C NMR (100 MHz, DMSO-d6) : 23.5(C-16), 53.3(C-3), 55.4(C-17),

55.6(C-6), 100.9(C-25), 104.8(C-15), 106.9(C-20), 108.3(C-23),


111.3(C-10), 118.1(C-13), 118.9(C-12), 119.3(C-24), 121.2(C-11),
125.7(C-14), 134.0(C-7), 136.2(C-19), 137.1(C-9), 146.0(C-22),
147.0(C-21), 164.6(C-4), 166.3(C-1)
Elemental Analysis (%) : 14.07(N), 62.38(C), 4.43(H), 0(S)

HPLC Chromatogram of Aminotadalafil

- 27 -

UV Spectrum of Aminotadalafil

IR Spectrum of Aminotadalafil

- 28 -

Mass spectrum of Aminotadalafil (EI+)


[M]+

Theoretical Ion Distribution of Aminotadalafil (EI+)


Molecular Formula : C21 H18 N4 O4
(m/z 390.1328, MW 390.3983, U.S. 15.0)
Base Peak : 390.1328, Averaged MW : 390.3995 (a), 390.4002 (w)
m/z
390.1328
391.1358
392.1385
393.1410
394.1435
395.1460
396.1485

INT.
100.0000 **********************************************************
25.2487 ***************
3.8568 **
0.4379
0.0399
0.0030
0.0002

Elemental Composition of Aminotadalafil (EI+)


Observed m/z
390.1324

Int%
100.0

Err[ppm
-11.4
-1.1
-7.9
+9.2
+2.4

/
/
/
/
/
/

mmu]
-4.4
-0.4
-3.1
+3.6
+0.9

- 29 -

Unsaturation
19.0
15.0
19.5
11.0
15.5

Composition
C 26 H 18 O
C 21 H 18 O
C 24 H 16 O
C 16 H 18 O
C 19 H 16 O

2N
4N
N5
6N
3N

2
4
6
7

1H-NMR

spectrum of Aminotadalafil (400MHz, DMSO)

12

13

14

11
10

15

17

19

25

18

24

NH 2

N
H

18

16

24 23

20

21

23
22

O
O

20

25

10
12
11

13

16
17

13C-NMR

spectrum of Aminotadalafil (100MHz, DMSO)

12

13

14

11
10

8
N
H

15

16

18
17
N

NH 2
N

19
20

24

21

23
22

O
O

25

24

1
4

21

22

9
19

14

11

12
13 10

23

20 25
15

6 17
3

- 30 -

16

epi-Aminotadalafil

: epi-aminotadalafil
/ : C21H18N4O4 / 390.39
: 2-amino-6-(1,3-benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydro(6S,12aR)-pyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione
O
NH2
N
N

N
H

O
O


HPLC RT (min) : 15.5
UV max (nm) : 283.7
IR (cm-1) : KBr. 3394(m), 1659(s), 1489(m), 1455(m), 1324(w),
1239(w), 1159(w), 1094(w), 1038(w), 932(w), 796(w), 745(w)
+

Mass (m/z) : EI+ (70eV). 390([M] , 100%), 374(23%), 318(23%),


289(70%), 269(20%), 263(72%), 233(27%), 204(43%), 169(23%)
- 31 -

1H NMR (100 MHz, DMSO-d6) : 2.95(1H, dd, J = 14.7, 12.3 Hz,


H-16), 3.29(1H, dd, J = 15.3, 4.3 Hz, H-16), 4.08(1H, d, J = 17.4
Hz, H-3), 4.14(1H, dd, J = 11.7, 4.1 Hz, H-17), 4.34(1H, d, J = 17.5
Hz, H-3), 5.76(2H, s, H-18), 6.00(1H, d, J = 0.7 Hz, H-25), 6.01(1H,
H-25), 6.62(1H, dd, J = 8.1, 1.5 Hz, H-24), 6.76(1H, d, J = 1.7 Hz,
H-20), 6.83(1H, s, H-6), 6.87(1H, d, J = 8.0 Hz, H-23), 7.02(1H, t, J
= 7.3 Hz, H-12), 7.11(1H, t, J = 7.6 Hz, H-11), 7.32(1H, d, J = 8.0
Hz, H-10), 7.50(1H, d, J = 7.8 Hz, H-13), 11.11(1H, br s, NH)

13

C NMR (100 MHz, DMSO-d6) : 26.7(C-16), 50.9(C-6), 51.8(C-17),

52.3(C-3), 101.3(C-25), 107.4(C-15), 108.2(C-20), 108.3(C-23),


111.4(C-10), 118.1(C-13), 118.9(C-12), 121.7(C-24), 121.7(C-11),
125.9(C-14), 130.3(C-7), 132.9(C-19), 136.3(C-9), 147.3(C-22),
147.6(C-21), 162.1(C-4), 162.8(C-1)
HPLC Chromatogram of epi-Aminotadalafil

- 32 -

UV Spectrum of epi-Aminotadalafil

IR Spectrum of epi-Aminotadalafil

- 33 -

Mass spectrum of epi-Aminotadalafil (EI+)


[M]+

Theoretical Ion Distribution of epi-Aminotadalafil (EI+)


Molecular Formula : C21 H18 N4 O4
(m/z 390.1328, MW 390.3983, U.S. 15.0)
Base Peak : 390.1328, Averaged MW : 390.3995 (a), 390.4002 (w)
m/z
390.1328
391.1358
392.1385
393.1410
394.1435
395.1460
396.1485

INT.
100.0000 **********************************************************
25.2487 ***************
3.8568 **
0.4379
0.0399
0.0030
0.0002

Elemental Composition of epi-Aminotadalafil (EI+)


Observed m/z
390.1324

Int%
100.0

Err[ppm
-11.4
-1.1
-7.9
+9.2
+2.4

/
/
/
/
/
/

mmu]
-4.4
-0.4
-3.1
+3.6
+0.9

- 34 -

Unsaturation
19.0
15.0
19.5
11.0
15.5

Composition
C 26 H 18 O
C 21 H 18 O
C 24 H 16 O
C 16 H 18 O
C 19 H 16 O

2N
4N
N5
6N
3N

2
4
6
7

1H-NMR

spectrum of epi -Aminotadalafil (400MHz, DMSO)

12

13

14

11
10

15

17

NH2

N
H

18

16

19
24

20

18

25

21

23
22

23
6

O
O

25

20

10
13

12
11

16

24
17

13C-NMR

spectrum of epi -Aminotadalafil (400MHz, DMSO)

12

13

14

11
10

15

N
H

16

18
17
N

19
24

20

22

O
O

NH2
N

21

23

21

25

22

9 19

14

11
20
23
25
24
12 13 10 15

17
3

- 35 -

6
16

Benzylsildenafil

: Benzylsildenafil
/ : C28H34N6O4S / 550.68
: 5-[5-(4-Benzyl-piperazine-1-sulfonyl)-2-ethoxy-phenyl]-1methyl-3-propyl-1,6-dihydro-pyrazolo [4,3-d]pyrimidin-7-one

HN

N
N
O


HPLC Rt (min) : 34.71
UV max (nm) : 291.25
-1

IR (cm ) : (CHCl3). 3319(w), 2957(w), 1698(s), 1598(w),


1490(w), 1455(w), 1351(m), 1167(m), 949(w), 814(w), 746(m), 700(w)
+

Mass (m/z) : EI+ (70eV). 550([M] , 19%), 459(16%), 404(84%),


395(18%), 311(26%), 283(18%), 282(5%), 254(15%), 175(100%),
132(36%), 91(100%), 72(18%)
- 36 -

H NMR (400MHz, DMSO-d6) : 0.91(3H, t, J = 7.4 Hz, H-13),


1.34(3H, t, J = 6.9 Hz, H-21), 1.72(2H, m, H-12), 2.43(4H, br m,
H-25, 27), 2.76(2H, t, J = 7.4 Hz, H-11), 2.91(4H, br m, H-24, 28),
3.45(2H, s, H-29), 4.16(3H, s, H-10), 4.21(2H, q, J = 6.9 Hz, H-20),
7.23(3H, m, H-31, 33, 35), 7.28(2H, m, H-32, 34), 7.37(1H, d, J = 8.7
Hz, H-18), 7.80(1H, m, H-17), 7.83(1H, m, H-15), 12.17(1H, br s, NH)

13

C NMR (100MHz, DMSO-d6) : 13.8(C-13), 14.2(C-21), 21.6(C-12),

27.1(C-11), 37.8(C-10), 45.9(C-24, 28), 51.4(C-25, 27), 61.3(C-29),


64.8(C-20), 113.2(C-18), 123.7(C-16), 124.4(C-9), 126.0(C-14),
127.0(C-33), 128.1(C-32, 34), 128.7(C-31, 35), 130.0(C-15),
131.4(C-17), 137.7(C-8, 30), 144.9(C-1), 148.1(C-6), 153.7(C-4),
159.9(C-19)
Elemental Analysis (%) : 15.20(N), 60.86(C), 6.24(H), 5.67(S)

- 37 -

- 38 -

[M]+

- 39 -

- 40 -

1H-NMR

Spectrum of Benzylsildenafil (400MHz, DMSO)

10

O
4
O
32
33

24
31
30

34

25

16

29

35

28

HN

O
15

14

10
N
N

6
N

20

18

27

12

11

19

17

21

13
21

13

31,33,35

29

32,34

25,27
24,28
11

15

13C-NMR

20
17

Spectrum of Benzylsildenafil (100MHz, DMSO)

10

4
O
32
33

24
31
30

34
35

12

18

25
29

S
N

16

15

18

27

1
11

19

17

28

14

HN

20

21

31,35 32,34

12
13

9
14

19

4 61

33
8,30 15
17

18
16

- 41 -

20

25,27
24,28 10

29

11

12

21

13

Demethylhongdenafil

/ : Demethylhongdenafil / Nor-acetildenafil
/ : C24H32N6O3 / 452.55
: 5-{2-Ethoxy-5-[2-(4-methyl-piperazine-1-yl)acetyl]phenyl}1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidine7-one
O

HN

N
N
N


HPLC RT (min) : 22.3
UV max (nm) : 276.28
-1

IR (cm ) : (CHCl3). 3316(w), 2936(w), 2801(w), 1695(s),


1603(m), 1494 (w), 1394 (w), 1246(m), 1147 (w), 1031 (w), 926 (w),
754(m)
+

Mass (m/z) : EI+ (70eV). 452([M] , 28%), 354(7%), 311(10%),


297(6%), 283(5%), 166(7%), 136(10%), 113(100%), 70(100%), 56(14%)

- 42 -

H NMR

(500MHz, DMSO-d6) : 0.94(3H, t, J = 7.4 Hz, H-13),

1.34(3H, t, J = 7.0 Hz, H-21), 1.75(2H, m, H-12), 2.12(3H, s, H-30),


2.37(4H, br m, H-26, 28), 2.50(4H, br m, H-25, 29), 2.79(2H, t, J =
7.4 Hz, H-11), 3.74(2H, s, H-23), 4.16(3H, s, H-10), 4.21(2H, q, J =
7.0 Hz, H-20), 7.23(1H, d, J = 8.8 Hz, H-18), 8.15(1H, dd, J = 8.8,
2.1 Hz, H-17), 8.27(1H, d, J = 2.1 Hz, H-15), 12.08(1H, br s, NH)

13

C NMR

(125MHz, DMSO-d6) : 13.8(C-13), 14.3(C-21),

21.7(C-12), 27.1(C-11), 37.8(C-10), 45.4(C-30), 52.6(C-25, 29),


54.4(C-26, 28), 64.0(C-23), 64.5(C-20), 112.3(C-18), 122.7(C-16),
124.3(C-9), 128.2(C-14), 131.1(C-15), 132.4(C-17), 137.9(C-8),
144.9(C-1), 148.8(C-6), 153.6(C-4), 160.1(C-19), 195.2(C-22)
Elemental Analysis (%) : 18.61(N), 63.11(C), 7.18(H), 0(S)

HPLC Chromatogram of Demethylhongdenafil


Chrom Ttpe : Fixed WL Chromatogram, 291nm

- 43 -

UV Spectrum of Demethylhongdenafil

RT

22.55 m in (S) Current Spectrum

IR Spectrum of Demethylhongdenafil

- 44 -

Mass Spectrum of Demethylhongdenafil (EI+)

[M]+

- 45 -

Theoretical Ion Distribution of Demethylhongdenafil (EI+)


Molecular Formula : C24 H32 N6 O3
(m/z 452.2536, MW 452.5565, U.S. 12.0)
Base Peak : 452.2536, Averaged MW : 452.5584 (a), 452.5591 (w)
m/z
452.2536
453.2565
454.2592
455.2618
456.2644
457.2699
458.2694

INT.
100.0000 **********************************************************
29.4920 *****************
4.7978 ***
0.5608
0.0517
0.0039
0.0003

Elemental Composition of Demethylhongdenafil (EI+)


Observed m/z
452.2531

Int%
42.3

Err[ppm
+5.9
-7.1
+7.8
+1.8
-4.1
-10.0
+10.7
+4.8
-1.1
-7.0
+7.8
+1.8
-1.5
+7.4
-5.6
+10.3
-2.7
-8.6
+6.2
+0.3
-5.6
+9.2

/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/

mmu]
+2.7
-3.2
+3.5
+0.8
-1.8
-4.5
+4.9
+2.2
-0.5
-3.2
+3.5
+0.8
-0.7
+3.3
-2.5
+4.7
-1.2
-3.9
+2.8
+0.1
-2.5
+4.2

- 46 -

Unsaturation
20.0
11.0
2.5
7.0
11.5
16.0
3.0
7.5
12.0
16.5
8.0
12.5
16.0
12.0
3.0
12.5
3.5
8.0
-0.5
4.0
8.5
0.0

Composition
C 35 H 32
C 28 H 36 O 5
C 20 H 38 O 10 N
C 23 H 36 O 7 N 2
C 26 H 34 O 4 N 3
C 29 H 32 O N 4
C 18 H 36 O 9 N 4
C 21 H 34 O 6 N 5
C 24 H 32 O 3 N 6
C 27 H 30 N 7
C 19 H 32 O 5 N 8
C 22 H 30 O 2 N 9
C 32 H 36 S
C 27 H 36 O 2 N 2 S
C 20 H 40 O 7 N 2 S
C 25 H 34 O N 5 S
C 18 H 38 O 6 N 5 S
C 21 H 36 O 3 N 6 S
C 13 H 38 O 8 N 7 S
C 16 H 36 O 5 N 8 S
C 19 H 34 O 2 N 9 S
C 11 H 36 O 7 N 10 S

1H-NMR

Spectrum of Demethylhongdenafil (500MHz, DMSO)

O
26

30

4
O

25

23

29

30

HN

15

28

10

10

14

22

12

11

19

17

25,29

20

18

21

21
26,28

23

13

13

11
15

20

17

12

18

13C-NMR

Spectrum of Demethylhongdenafil (125MHz, DMSO)

O
26

30

4
O

25

29

23

HN
15

28

22

10

N
14

18

1
11

19

17

20

21

15

22

19

1
4 6

12
13

26,28
25,29

17 14
9

18
16

- 47 -

20
23

30

10

11 12
21 13

Dimethylsildenafil

/ : Dimethylsildenafil / Methisosildenafil
/

: C23H32N6O4S / 488.60

: 1-[[3-(4,7-Dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d]pyrimidine-5-yl)-4-ethoxyphenyl]sulfonyl]-3,5dimethylpiprazine
O

HN

N
HN
O


HPLC RT (min) : 29.73
UV max (nm) : 292.13
-1

IR (cm ) : (CHCl3). 3316(w), 2963(w), 1698(s), 1599(w),


1489(w), 1347(w), 1247(w), 1167(m), 1014(w), 928(w), 754(w)
+

Mass (m/z) : EI+ (70eV). 488([M] , 11%), 487(8%), 377(5%),


312(63%), 311(45%), 283(33%) , 254(9%), 225(5%), 166(5%),
113(100%), 84(44%), 70(93%)

- 48 -

H NMR (400MHz, DMSO-d6) : 0.92(9H, m, H-13, 29, 30),


1.33(3H, t, J = 6.8 Hz, H-21), 1.77(4H, m, H-24, 28, 12), 2.77(4H, m,
H-25, 27, 11), 3.45(2H, m, H-24, 28), 4.16(3H, s, H-10), 4.21(2H, m,
H-20), 7.36(1H, d, J = 8.4 Hz, H-18), 7.81(1H, m, H-17), 7.86(1H, m,
H-15), 12.14(2H, br s, NH)

13

C NMR (100MHz, DMSO-d6) : 13.8(C-13), 14.2(C-21), 18.8(C-29,

30), 21.6(C-12), 27.2(C-11), 37.8(C-10), 49.6(C-25, 27), 51.7(C-24, 28),


64.8(C-20), 113.1(C-18), 123.5(C-16), 124.4(C-9), 126.5(C-14),
129.8(C-15), 131.3(C-17), 137.7(C-8), 144.9(C-1), 148.1(C-6),
153.6(C-4), 159.7(C-19)
Elemental Analysis (%) : 17.24(N), 56.02(C), 6.72(H), 6.65(S)

HPLC Chromatogram of Dimethylsildenafil


Chrom Ttpe : Fixed WL Chromatogram, 291nm

- 49 -

UV Spectrum of Dimethylsildenafil

RT

29.73min (S) Current Spectrum

IR Spectrum of Dimethylsildenafil

- 50 -

Mass Spectrum of Dimethylsildenafil (EI+)

[M]+

- 51 -

Theoretical Ion Distribution of Dimethylsildenafil (EI+)


Molecular Formula : C23 H32 N6 O4 S
(m/z 488.2206, MW 488.6109, U.S. 12.0)
Base Peak : 488.2206, Averaged MW : 488.6110 (a), 488.6120 (w)
m/z
488.2206
489.2234
490.2214
491.2223
492.2233
493.2247
494.2262
495.2279

INT.
100.0000
29.2072
9.3484
1.8657
0.2887
0.0361
0.0038
0.0003

**********************************************************
*****************
*****
*

Elemental Composition of Dimethylsildenafil (EI+)


Observed m/z
488.2212

Int%
100.0

Err[ppm
+2.7
-2.8
+5.4
-6.6
-0.1
+8.2
-3.9
-9.4
-1.1
-6.6
+7.8
-4.2
-9.7
+4.0
-1.5
-7.0
+6.8
+1.3
-4.2
+9.5
+4.0
-8.0
-1.5

/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/

mmu]
+1.3
-1.4
+2.6
-3.2
+0.0
+4.0
-1.9
-4.6
-0.5
-3.2
+3.8
-2.1
-4.7
+2.0
-0.7
-3.4
+3.3
+0.6
-2.1
+4.6
+2.0
-3.9
-0.7

- 52 -

Unsaturation
15.0
19.5
15.5
6.5
20.0
16.0
7.0
11.5
7.5
12.0
20.0
11.0
15.5
7.0
11.5
16.0
7.5
12.0
16.5
8.0
12.5
3.5
17.0

Composition
C 30 H 32 O 6
C 33 H 30 O 3 N
C 28 H 30 O 5 N 3
C 21 H 34 O 10 N 3
C 31 H 28 O 2 N 4
C 26 H 28 O 4 N 6
C 19 H 32 O 9 N 6
C 22 H 30 O 6 N 7
C 17 H 30 O 8 N 9
C 20 H 28 O 5 N 10
C 34 H 32 O S
C 27 H 36 O 6 S
C 30 H 34 O 3 N S
C 22 H 36 O 8 N 2 S
C 25 H 34 O 5 N 3 S
C 28 H 32 O 2 N 4 S
C 20 H 34 O 7 N 5 S
C 23 H 32 O 4 N 6 S
C 26 H 30 O N 7 S
C 18 H 32 O 6 N 8 S
C 21 H 30 O 3 N 9 S
C 14 H 34 O 8 N 9 S
C 24 H 28 N 10 S

1H-NMR

Spectrum of Dimethylsildenafil (400MHz, DMSO)

13,29,30
10
O

10

4
O
29

25

24

15

S
N

HN
27

N
14

11
20

18

24,28,12

19

17

28

HN

12

21
13

21

25,27,11

30

15

20

18

24,28

17
5,26

13C-NMR

Spectrum of Dimethylsildenafil (100MHz, DMSO)

10

4
O
29

25

24

15

N
14

HN

28

HN

1
11

19

17

27

18

20

21

12
13

30

25,27

14

24,28
19

15

1
8 17
4 6

18
16

- 53 -

20

29,30
12
10 11 21 13

Homosildenafil

: Homosildenafil
/ : C23H32N6O4S / 488.62
: 1-[[3-(4,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d]-pyrimidine-5-yl)-4-ethoxyphenyl]-sulfonyl]-4-ethylPiperazine
O

HN

S
N

N
O


HPLC RT (min) : 15.20
UV max (nm) : 214.4, 295.9
-1

IR (cm ) : (CHCl3). 3309(w), 2964(w), 1696(s), 1594(w),


1490(w), 1393(w), 1351(w), 1166(m), 1030(w), 954(w), 742(w)
+

Mass (m/z) : EI+ (70eV). 488([M] , 26%), 404(79%), 312(31%),


283(30%), 113(100%), 98(23%), 84(18%), 70(54%), 56(51%)
- 54 -

1H NMR (400 MHz, DMSO-d6) : 0.91(3H, t, J = 7.1 Hz, H-30),


0.92(3H, t, J = 7.4 Hz, H-13), 1.33(3H, t, J = 6.9 Hz, H-21), 1.73(2H,
m, H-12), 2.28(2H, q, J = 7.1 Hz, H-29), 2.40(4H, br m, H-25,27),
2.76(2H, t, J = 7.5 Hz, H-11), 2.89(4H, br m, H-24,28), 4.16(3H, s,
H-10), 4.21(2H, q, J = 6.9 Hz, H-20), 7.37(1H, d, J = 8.7 Hz, H-18),
7.82(1H, dd, J = 8.6, 2.4 Hz, H-17), 7.84(1H, d, J = 2.4 Hz, H-15),
12.16(1H, br s, NH)

13

C NMR (100 MHz, DMSO-d6) : 11.8(C-30), 13.8(C-13), 14.2(C-21),

21.7(C-12), 27.1(C-11), 37.8(C-10), 45.9(C-24,28), 51.0(C-29),


51.2(C-25,27), 64.8(C-20), 113.2(C-18), 123.7(C-16), 124.4(C-9),
126.0(C-14), 130.0(C-15), 131.5(C-17), 137.8(C-8), 144.9(C-1),
148.1(C-6), 153.7(C-4), 159.9(C-19)
Elemental Analysis (%) : C(56.51), H(6.61), N(17.38), S(6.55)
HPLC Chromatogram of Homosildenafil

- 55 -

UV Spectrum of Homosildenafil

IR spectrum of Homosildenafil

- 56 -

Mass spectrum of Homosildenafil (EI+)

[M]+

Theoretical Ion Distribution of Homosildenafil (EI+)


Molecular Formula : C23 H32 N6 O4 S
(m/z 488.2206, MW 488.6109, U.S. 12.0)
Base Peak : 488.2206, Averaged MW : 488.6110 (a), 488.6120 (w)
m/z
488.2206
489.2234
490.2214
491.2223
492.2233
493.2247
494.2262
495.2279

INT.
100.0000
29.2072
9.3484
1.8657
0.2887
0.0361
0.0038
0.0003

**********************************************************

*****************
*****
*

Elemental Composition of Homosildenafil (EI+)


Observed m/z
488.2200

Int%
17.2

Err[ppm
-3.9
-9.4
-1.1
-6.6
+7.1

/
/
/
/
/
/

mmu]
-1.9
-4.6
-0.5
-3.2
+3.5

Unsaturation
11.5
16.0
12.0
16.5
8.0

- 57 -

Composition
C 25 H 34 O
C 28 H 32 O
C 23 H 32 O
C 26 H 30 O
C 18 H 32 O

5N
2N
4N
N7
6N

3
4
6
S
8

S
S
S
S

1H-NMR

spectrum of Homosildenafil (400MHz, DMSO)

10

4
O

24
25
30

15

14

29

HN

28

20

18

27

21

N2

17

13,30

10
9

1
11

12

21
13
15
24
28

20
18

17

25
11 27

12

29

13C-NMR

spectrum of Homosildenafil (100MHz, DMSO)

10

24
25
30

15

14

29

HN

28

20

18

27

N
N2

17

1
11

12
12

25
24
27
28

21
13

13
10

29
14

19

15
4

17

9
16

20

18

- 58 -

11

21 30

Hongdenafil

/ : Hongdenafil / Acetildenafil
/ : C25H34N6O3 / 466.58
: 5-[2-ethoxy-5-[(4-ethyl-1-piperazinyl)acetyl]phenyl]-1,4dihydro-1-methyl-3-propyl-7H-Pyrazolo[4,3-d]pyrimidine-7one
O

HN

N
N
N


HPLC RT (min) : 8.8
UV max (nm) : 234.6, 289.2
-1

IR (cm ) : (CHCl3). 3315(w), 2962(w), 2815(w), 1693(s),


1604(w), 1494(w), 1393(w), 1258(w), 1163(w), 1031(w), 752(w)
Mass (m/z) : EI+ (70eV). 466([M]+, 76%), 409(9%), 354(29%),
339(16%), 326(10%), 311(40%), 297(27%), 166(24%), 127(100%),
112(55%), 98(40%), 84(75%), 70(74%), 56(47%)

- 59 -

1H NMR (400 MHz, DMSO-d6) : 0.94(3H, t, J = 7.4 Hz, H-13),


0.98(3H, t, J = 7.2 Hz, H-31), 1.34(3H, t, J = 6.9 Hz, H-21), 1.74(2H,
m, H-12), 2.29(2H, q, J = 7.1 Hz, H-30), 2.38(4H, br m, H-26,28),
2.50(4H, br m, H-25,29), 2.79(2H, t, J = 7.5 Hz, H-11), 3.74(2H, s,
H-23), 4.16(3H, s, H-10), 4.20(2H, q, J = 7.0 Hz, H-20), 7.24(1H, d, J

= 8.8Hz, H-18), 8.16(1H, dd, J = 8.8, 2.2 Hz, H-17), 8.27(1H, d, J =


2.2 Hz, H-15), 12.14(1H, br s, NH)

13

C NMR (100 MHz, DMSO-d6) : 12.0(C-31), 13.8(C-13), 14.3(C-21),

21.8(C-12), 27.2(C-11), 37.8(C-10), 51.6(C-26,28), 52.3(C-30),


52.8(C-25,29), 64.3(C-23), 64.6(C-20), 112.3(C-18), 122.8(C-16),
124.3(C-9), 128.2(C-14), 131.2(C-15), 132.5(C-17), 137.9(C-8),
144.9(C-1), 148.9(C-6), 153.8(C-4), 160.1(C-19), 195.3(C-22)
Elemental Analysis (%) : 18.19(N), 63.86(C), 7.30(H), 0(S)
HPLC Chromatogram of Hongdenafil

- 60 -

UV Spectrum of Hongdenafil

IR spectrum of Hongdenafil

- 61 -

Mass spectrum of Hongdenafil (EI+)

[M]+

Theoretical Ion Distribution of Hongdenafil (EI+)


Molecular Formula : C25 H34 N6 O3
(m/z 466.2692, MW 466.5834, U.S. 12.0)
Base Peak : 466.2692, Averaged MW : 466.5854 (a), 466.5861 (w)
m/z
466.2692
467.2722
468.2749
469.2776
470.2801
471.2827
472.2852

INT.
100.0000 **********************************************************
30.6343 ******************
5.1350 ***
0.6157
0.0581
0.0045
0.0003

Elemental Composition of Hongdenafil (EI+)


Observed m/z
466.2713

Int%
100.0

Err[ppm
+1.5
-4.3
+10.1
+4.4

/
/
/
/
/

mmu]
+0.7
-2.0
+4.7
+2.0

- 62 -

Unsaturation
11.5
16.0
7.5
12.0

Composition
C 27 H 36 O
C 30 H 34 O
C 22 H 36 O
C 25 H 34 O

4N3
N4
6N5
3N6

1H-NMR

spectrum of Hongdenafil (400MHz, DMSO)

10
10

30

26
N

31

25

15

28

14

23

29

HN

17

18

N
N2

12

11

20

31 13

21

21

13
23

15

11

20

18
17

26
28
25
12
29 30

13C-NMR

spectrum of Hongdenafil (100MHz, DMSO)

10

30
31

26
N

25

28
29

HN

15

14

23
17

18

N
N2

20

1
11

12
13

21

13

30

25 26
29 28
14

22

19

15
8 17

23
16

- 63 -

10

21

11
31

20

18

12

Hydroxyhomosildenafil

: Hydroxyhomosildenafil
/ : C23H32N6O5S / 504.62
: 4-[[3-(4,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo-(4,3-d]pyrimidin-5-yl)-4-ethoxyphenyl]sulfonyl]-1-Piperazineethanol
O

HN

S
N

N
HO


HPLC RT (min) : 13.6
UV max (nm) : 214.4, 295.9
-1

IR (cm ) : (CHCl3). 3314(w), 2955(w), 1696(s), 1595(w),


1490(w), 1394(w), 1350(w), 1166(m), 952(w), 740(w)
Mass (m/z) : FAB+ (m-NBA). 527([M+Na]+, 10%), 505([M+H]+,
100%), 486(8%), 473(15%), 404(11%), 312(9%), 283(3%), 129(20%),
99(13%), 56(5%)

- 64 -

1H NMR (400 MHz, DMSO-d6) : 0.94(3H, t, J = 7.4 Hz, H-13),


1.33(3H, t, J = 6.9 Hz, H-21), 1.74(2H, m, H-12), 2.36(2H, q, J = 5.8
Hz, H-29), 2.48(4H, br m, H-25,27), 2.77(2H, t, J = 7.5 Hz, H-11),
2.88(4H, br m, H-24,28), 3.42(2H, t, J = 5.8 Hz, H-30), 4.16(3H, s,
H-10), 4.21(2H, q, J = 6.9 Hz, H-20), 4.39(1H, br s, OH), 7.38(1H, d,

J = 8.6 Hz, H-18), 7.82(1H, dd, J = 8.6, 2.3 Hz, H-17), 7.85(1H, d, J
= 2.3 Hz, H-15), 12.23(1H, br s, NH)

13

C NMR (100 MHz, DMSO-d6) : 13.9(C-13), 14.3(C-21), 21.7(C-12),

27.2(C-11), 37.9(C-10), 45.9(C-24,28), 51.9(C-25,27), 58.4(C-29),


59.5(C-30), 64.9(C-20), 113.2(C-18), 123.7(C-16), 124.4(C-9),
125.8(C-14), 130.0(C-15), 131.6(C-17), 137.8(C-8), 145.0(C-1),
148.2(C-6), 153.8(C-4), 159.9(C-19)
Elemental Analysis (%) : 16.76(N), 54.74(C), 6.39(H), 6.51(S)
HPLC Chromatogram of Hydroxyhomosildenafil

- 65 -

UV Spectrum of Hydroxyhomosildenafil

IR spectrum of Hydroxyhomosildenafil

- 66 -

Mass spectrum of Hydroxyhomosildenafil (FAB+)


[M+H]+

Theoretical Ion Distribution of Hydroxyhomosildenafil (FAB+)


Molecular Formula : C23 H33 N6 O5 S
(m/z 505.2233, MW 505.6182, U.S. 11.5)
Base Peak : 505.2233, Averaged MW : 505.6183 (a), 505.6193 (w)
m/z
505.2233
506.2261
507.2242
508.2252
509.2262
510.2276
511.2292
512.2308

INT.
100.0000
29.2603
9.5644
1.9292
0.3084
0.0400
0.0044
0.0004

**********************************************************
*****************
******
*

Elemental Composition of Hydroxyhomosildenafil (FAB+)


Observed m/z
505.2236

Int%
100.0

Err[ppm
+4.6
-9.6
-7.0
+3.3
-2.0
+5.9
+0.6
+3.3
+8.2
-8.7
-6.0
-8.7

/
/
/
/
/
/
/
/
/
/
/
/
/

mmu]
+2.3
-4.9
-3.5
+1.7
-1.0
+3.0
+0.3
+1.7
+4.2
-4.4
-3.1
-4.4

- 67 -

Unsaturation
15.0
11.0
11.5
6.5
11.0
7.0
11.5
12.0
11.5
7.0
7.5
12.5

Composition
C 28 H 31 O
C 22 H 31 O
C 20 H 29 O
C 22 H 37 O
C 25 H 35 O
C 20 H 35 O
C 23 H 33 O
C 21 H 31 O
C 26 H 37 O
C 22 H 39 O
C 20 H 37 O
C 21 H 33 O

6N3
7N7
6 N 10
9N2S
6N3S
8N5S
5N6S
4N9S
4N2S2
6N3S2
5N6S2
N 10 S 2

1H-NMR

spectrum of Hydroxyhomosildenafil (400MHz, DMSO)

10

4
24
30
HO

15

25

29

14

17

28

HN

18

27

21

10

N
N2

1
11

20

21

12
13

15
20

30

24
28

25
11 27

29

18

17

12

OH

13C-NMR

spectrum of Hydroxyhomosildenafil (100MHz, DMSO)

10

4
24
30
HO

15

25

14

17

28

18

27

29

HN

N
N2

20

1
11

21

12
13

12

13
21

10

25
27

19

1
6

15 14
17

916

24
28

20

18

30
29

- 68 -

11

13

Hydroxyhongdenafil

/ : Hydroxyhongdenafil / Hydroxyacetildenafil
/ : C25H34N6O4 / 482.58
: 5-[2-Ethoxy-5-[2-(4-(2-hydroxyethylpiperazine-1-yl)acetyl]
phenyl]-1-methyl-3-propyl-1,6-dihydropyrazolo[4,3-d]pyrimidine-7-one
O
HO
N

HN

N
N


HPLC RT (min) : 22.03
UV max (nm) : 276.33
IR (cm-1) : (CHCl3). 3314(w), 2937(w), 2818(w), 1694(s),
1504(w), 1495(w), 1394(w), 1245(w), 1155(w), 1030(w), 929(w), 752(w)
+

Mass (m/z) : EI+ (70eV). 482([M] , 32%), 464(11%), 395(5%),


354(9%), 311(12%), 297(9%), 283(6%), 212(10%), 143(100%),
141(17%), 100(65%), 70(67%), 56(21%)

- 69 -

1H NMR (400MHz, DMSO-d6) : 0.93(3H, t, J = 7.4 Hz, H-13),


1.33(3H, t, J = 6.9 Hz, H-21), 1.78(2H, m, H-12), 2.38(2H, m, H-30),
2.50(8H, m, H-25, 26, 28, 29), 2.79(2H, t, J = 7.5 Hz, H-11), 3.48(2H,
t, J = 6.2 Hz, H-31), 3.73(2H, s, H-23), 4.16(3H, s, H-10), 4.19(2H, q,

J = 7.0 Hz, H-20), 7.23(1H, d, J = 8.9 Hz, H-18), 8.14(1H, dd, J =


8.8, 2.2 Hz, H-17), 8.27(1H, d, J = 2.1 Hz, H-15), 12.08(1H, br s,
NH)

13

C NMR (100MHz, DMSO-d6) : 13.8(C-13), 14.3(C-21), 21.7(C-12),

27.1(C-11), 37.8(C-10), 52.7(C-25, 29), 53.0(C-26, 28), 58.3(C-31),


60.1(C-30), 64.2(C-23), 64.6(C-20), 112.3(C-18), 122.8(C-16),
124.3(C-9), 128.2(C-14), 131.2(C-15), 132.5(C-17), 137.9(C-8),
144.9(C-1), 148.9(C-6), 153.7(C-4), 160.1(C-19), 195.3(C-22)
Elemental Analysis (%) : 17.16(N), 60.98(C), 7.17(H), 0(S)

HPLC Chromatogram of Hydroxyhongdenafil


Chrom Ttpe : Fixed WL Chromatogram, 223 nm

- 70 -

UV Spectrum of Hydroxyhongdenafil

RT 22.03 min (S) Current Spectrum

IR Spectrum of Hydroxyhongdenafil

- 71 -

- 72 -

Theoretical Ion Distribution of Hydroxyhongdenafil (EI+)


Molecular Formula : C25 H34 N6 O4
(m/z 482.2642, MW 482.5828, U.S. 12.0)
Base Peak : 482.2642, Averaged MW : 482.5847 (a), 482.5854 (w)
m/z
482.2642
483.2671
484.2698
485.2724
486.2749
487.2774
488.2799

INT.
100.0000 **********************************************************
30.6724 ******************
5.3471 ***
0.6791
0.0686
0.0058
0.0004

Elemental Composition of Hydroxyhongdenafil (EI+)


Observed m/z
482.2653

Int%
100.0

Err[ppm
+8.9
-3.3
-8.8
+5.1
-0.5
-6.1
+7.8
+2.3
-9.9
-3.3
+5.1
-7.1
-0.5
+1.9
-10.3
+10.3
-1.9
+4.7
-7.5
+0.9
-4.7
-10.3
+9.2
+3.6
-1.9
-7.5

/ mmu]
/ +4.3
/ -1.6
/ -4.3
/ +2.4
/ -0.2
/ -2.9
/ +3.8
/ +1.1
/ -4.8
/ -1.6
/ +2.4
/ -3.4
/ -0.2
/ +0.9
/ -5.0
/ +4.9
/ -0.9
/ +2.3
/ -3.6
/ +0.4
/ -2.3
/ -4.9
/ +4.4
/ +1.8
/ -0.9
/ -3.6

- 73 -

Unsaturation
20.0
11.0
15.5
7.0
11.5
16.0
7.5
12.0
3.0
16.5
12.5
3.5
17.0
16.0
7.0
12.0
3.0
16.5
7.5
3.5
8.0
12.5
-0.5
4.0
8.5
13.0

Composition
C 36 H 34 O
C 29 H 38 O 6
C 32 H 36 O 3 N
C 24 H 38 O 8 N 2
C 27 H 36 O 5 N 3
C 30 H 34 O 2 N 4
C 22 H 36 O 7 N 5
C 25 H 34 O 4 N 6
C 18 H 38 O 9 N 6
C 28 H 32 O N 7
C 23 H 32 O 3 N 9
C 16 H 36 O 8 N 9
C 26 H 30 N 10
C 33 H 38 O S
C 26 H 42 O 6 S
C 28 H 38 O 3 N 2 S
C 22 H 42 O 8 N 2 S
C 31 H 36 N 3 S
C 24 H 40 O 5 N 3 S
C 19 H 40 O 7 N 5 S
C 22 H 38 O 4 N 6 S
C 25 H 36 O N 7 S
C 14 H 40 O 9 N 7 S
C 17 H 38 O 6 N 8 S
C 20 H 36 O 3 N 9 S
C 23 H 34 N 10 S

1H-NMR

Spectrum of Hydroxyhongdenafil (400MHz, DMSO)

10

O
HO

30

31

26

4
25

28

O
23

29

HN

13

10
N

21

15

14

22

25,26,28,29

1
12

11

17
O

18

20

23

21

13

31
20

15

11 30
12

18
17
5

13C-NMR

Spectrum of Hydroxyhongdenafil (100MHz, DMSO)

O
HO

31

30

26

4
25

28

O
23

29

10
9

HN

15

14

22

18

20

21

4 6

17

12
13

25,29

23

15

19

1
11

17

22

26,28

14 916

18

- 74 -

20 3031

10

11 12

21

13

Hydroxyvardenafil

: Hydroxyvardenafil
/ : C23H32N6O5S / 504.60
: 1-[[3-(1,4-Dihydro-5-methyl-4-oxo-7-propylimidazo[5,1-f]
[1,2,4]triazin-2-yl)-4-ethoxyphenyl]sulfonyl]-1-piperazineethanol
O

HN
N
N

S
N

N
N
O

HO


HPLC RT (min) : 20.9
UV max (nm) : 216
IR (cm-1) : (CHCl3). 3331(w), 2932(m), 1695(s), 1624(m),
1471(m), 1415(w), 1282(m), 1166(m), 1034(w), 951(w), 817(w), 754(m)
Mass (m/z) : EI+ (70eV). 504([M]+, 7%), 473(100%), 312(8%),
283(12%), 223(13%), 129(100%), 99(17%), 56(20%)

- 75 -

1H NMR (500MHz, DMSO-d6) : 0.94(3H, t, J = 7.4 Hz, H-13),


1.35(3H, t, J = 6.8 Hz, H-21), 1.72(2H, m, H-12), 2.36(2H, q, J = 4.8
Hz, H-29), 2.47(7H, m, H-10, 25, 27), 2.82(2H, m, H-11), 2.88(4H, br
m, H-24, 28), 3.42(2H, t, J = 4.8 Hz, H-30), 4.21(2H, q, J = 6.8 Hz,
H-20), 4.35(1H, br s, OH), 7.38(1H, d, J = 7.0 Hz, H-18), 7.84(1H, s,
H-15), 7.86(1H, d, J = 7.0 Hz, H-17), 11.65(1H, br s, NH)

13

C NMR (125MHz, DMSO-d6) : 13.6(C-21), 14.2(C-10, 13),

20.2(C-12), 27.1(C-11), 45.8(C-24, 28), 52.0(C-25, 27), 58.4(C-30),


59.5(C-29), 64.9(C-20), 113.1(C-18), 113.6(C-9), 120.8(C-16),
126.0(C-14), 130.1(C-15), 132.1(C-17), 137.6(C-3), 144.3(C-1),
146.1(C-6), 155.0(C-4), 160.2(C-19)
Elemental Analysis (%) : 16.19(N), 52.69(C), 6.54(H), 6.16(S)

HPLC Chromatogram of Hydroxyvardenafil


Chrom Ttpe : Fixed WL Chromatogram, 291 nm

- 76 -

UV Spectrum of Hydroxyvardenafil

RT 20.9 min (S) Current Spectrum

IR Spectrum of Hydroxyvardenafil

- 77 -

- 78 -

Theoretical Ion Distribution of Hydroxyvardenafil (EI+)


Molecular Formula : C23 H32 N6 O5 S
(m/z 504.2155, MW 504.6103, U.S. 12.0)
Base Peak : 504.2155, Averaged MW : 504.6103 (a), 504.6113 (w)
m/z
504.2155
505.2183
506.2164
507.2174
508.2184
509.2198
510.2213
511.2230

INT.
100.0000
29.2453
9.5600
1.9278
0.3081
0.0400
0.0044
0.0004

**********************************************************
*****************
******
*

Elemental Composition of Hydroxyvardenafil (EI+)


Observed m/z
504.2147

Int%
100.0

Err[ppm
-0.3
-5.6
+7.7
+2.4
-2.9
+5.0
-6.6
+7.7
-3.9
-9.3
+4.7
-7.0
+1.0
-4.3
-9.6
+3.7
-1.6
-7.0
+6.3
+1.0
-4.3

/ mmu]
/ -0.1
/ -2.8
/ +3.9
/ +1.2
/ -1.5
/ +2.5
/ -3.3
/ +3.9
/ -2.0
/ -4.7
/ +2.4
/ -3.5
/ +0.5
/ -2.2
/ -4.9
/ +1.9
/ -0.8
/ -3.5
/ +3.2
/ +0.5
/ -2.2

- 79 -

Unsaturation
15.0
19.5
11.0
15.5
20.0
16.0
7.0
16.5
7.5
12.0
20.0
11.0
7.0
11.5
16.0
7.5
12.0
16.5
8.0
12.5
17.0

Composition
C 30 H 32 O
C 33 H 30 O
C 25 H 32 O
C 28 H 30 O
C 31 H 28 O
C 26 H 28 O
C 19 H 32 O
C 24 H 26 O
C 17 H 30 O
C 20 H 28 O
C 34 H 32 O
C 27 H 36 O
C 22 H 36 O
C 25 H 34 O
C 28 H 32 O
C 20 H 34 O
C 23 H 32 O
C 26 H 30 O
C 18 H 32 O
C 21 H 30 O
C 24 H 28 O

7
4N
9N2
6N3
3N4
3N4
10 N 6
4N9
9N9
6 N 10
2S
7S
9N2S
6N3S
3N4S
8N5S
5N6S
2N7S
7N8S
4N9S
N 10 S

1H-NMR

Spectrum of Hydroxyvardenafil (500MHz, DMSO)

10

4
O
24
25
30
29

HO

HN

O
15

S
N

18

27

20

13

12

11

19

17

28

14

10,25,27

13

21

21

24,28

15
11

20
5

13C-NMR

OH

spectrum of Hydroxyvardenafil (125MHz, DMSO)

10

4
O
24
25
30
HO

12

30

18

17

29

29

15

S
N

14

18

27

1
11

19

17

28

HN

20

21

12
13

24,28
25,27
19
4

1
6

1514
18
17
16 9

- 80 -

30

20 29

10,13

11

12

21

Norneosildenafil

: Norneosildenafil
C22H29N5O4S

M.W. = 459.56

: 1-[[3-(4,7-Dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo
[4,3-d]pyrimidine-5-yl)-4-ethoxyphenyl]sulfonyl]piperizine
O

HN

S
N

N
O


HPLC RT (min) : 42.12
UV max (nm) : 291.48
-1

IR (cm ) : (CHCl3). 3306(w), 2939(w), 1693(s), 1558(w),


1488(w), 1340(m), 1279(w), 1167(m), 1028(w), 930(w), 818(w), 755(w)
+

Mass (m/z) : EI+ (70eV). 459([M] , 100%), 431(77%), 387(8%),


312(27%), 283(23%), 282(14%) , 254(10%), 166(25%), 136(18%),
84(25%), 55(7%)

- 81 -

1H NMR (400MHz, DMSO-d6) :

0.92(3H, t, J = 7.4 Hz, H-13),

1.32(3H, t, J = 7.0 Hz, H-21), 1.37(2H, br m, H-26), 1.54(4H, br m,


H-25, 27), 1.75(2H, m, H-12), 2.77(2H, t, J = 7.5 Hz, H-11), 2.91(4H,
br m, H-24, 28), 4.16(3H, s, H-10), 4.21(2H, q, J = 7.0 Hz, H-20),
7.36(1H, d, J = 8.8 Hz, H-18), 7.82(1H, d, J = 8.8 Hz, H-17),
7.88(1H, s, H-15), 12.14(1H, br s, NH)

13

C NMR (100MHz, DMSO-d6) : 13.7(C-13), 14.2(C-21), 21.6(C-12),

22.9(C-26), 24.6(C-25, 27), 27.1(C-11), 37.8(C-10), 46.5(C-24, 28),


64.8(C-20), 113.2(C-18), 123.4(C-16), 124.3(C-9), 127.2(C-14),
129.7(C-15), 131.2(C-17), 137.7(C-8), 144.9(C-1), 148.1(C-6),
153.6(C-4), 159.6(C-19)
Elemental Analysis (%) : 15.40(N), 57.22(C), 6.45(H), 7.07(S)

HPLC Chromatogram of Norneosildenafil


Chrom Ttpe : Fixed WL Chromatogram, 291 nm

- 82 -

UV Spectrum of Norneosildenafil

RT 42.12 min (S) Current Spectrum

IR Spectrum of Norneosildenafil

- 83 -

- 84 -

Theoretical Ion Distribution of Norenosildenafil (EI+)


Molecular Formula : C22 H29 N5 O4 S
(m/z 459.1940, MW 459.5694, U.S. 12.0)
Base Peak : 459.1940, Averaged MW : 459.5693 (a), 459.5704 (w)
m/z
459.1940
460.1969
461.1947
462.1957
463.1967
464.1981
465.1996
466.2013

INT.
100.0000
27.6826
8.9216
1.7283
0.2619
0.0320
0.0033
0.0003

**********************************************************
****************
*****
*

Elemental Composition of Norneosildenafil (EI+)


Observed m/z
459.1934

Int%
33.8

Err[ppm
-5.7
+8.9
+3.1
-9.7
-2.7
+6.0
-6.8
+8.9
-3.8
-9.7
+4.9
+1.6
-4.2
-10.1
+10.4
+4.5
-1.3
-7.2
+7.4
+1.6
-4.2
+10.4
-2.4

/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/

mmu]
-2.6
+4.1
+1.4
-4.5
-1.3
+2.8
-3.1
+4.1
-1.8
-4.4
+2.3
+0.7
-1.9
-4.6
+4.8
+2.1
-0.6
-3.3
+3.4
+0.7
-1.9
+4.8
-1.1

- 85 -

Unsaturation
19.5
11.0
15.5
6.5
20.0
16.0
7.0
16.5
7.5
12.0
3.5
7.0
11.5
16.0
3.0
7.5
12.0
16.5
8.0
12.5
17.0
8.5
-0.5

Composition
C 32 H 27 O 3
C 24 H 29 O 8 N
C 27 H 27 O 5 N 2
C 20 H 31 O 10 N 2
C 30 H 25 O 2 N 3
C 25 H 25 O 4 N 5
C 18 H 29 O 9 N 5
C 23 H 23 O 3 N 8
C 16 H 27 O 8 N 8
C 19 H 25 O 5 N 9
C 11 H 27 O 10 N 10
C 21 H 33 O 8 N S
C 24 H 31 O 5 N 2 S
C 27 H 29 O 2 N 3 S
C 16 H 33 O 10 N 3 S
C 19 H 31 O 7 N 4 S
C 22 H 29 O 4 N 5 S
C 25 H 27 O N 6 S
C 17 H 29 O 6 N 7 S
C 20 H 27 O 3 N 8 S
C 23 H 25 N 9 S
C 15 H 27 O 5 N 10 S
C 8 H 31 O 10 N 10 S

1H-NMR

Spectrum of Norneosildenafil (400MHz, DMSO)

10
O

10

4
O
24

O
15

25

N
14

13

21

12

11
20

18

27

19

17

28

26

HN

21

13

26

24,28 25,27

15
17

13C-NMR

11

20

18

12

Spectrum of Norneosildenafil (100MHz, DMSO)

O
4
O
24
25

15

S
N
28

26
27

HN

10

N
14

19

17

11
O

18

20

21

12
13

26
25,27

24,28

15

10
19
4 6

18
17 149
8
16

- 86 -

20

12
11

21 13

Piperidinohongdenafil

/ : Piperidinohongdenafil / Piperidinoacetildenafil
/ : C24H31N5O3 / 437.53
: 5-{2-Ethoxy-5-[2-piperidine-1-yl-acetyl]-phenyl}-1-methyl
-3-propyl-1,6-dihydro-pyrazolo[4,3-d]-pyrimidine-7-one
O
O

HN

N
N


HPLC RT (min) : 26.08
UV max (nm) : 276.54
IR (cm-1) : (CHCl3). 3310(w), 2935(m), 1691(s), 1561(w), 1494(w),
1393(w), 1260(w), 1149(w), 1033(w), 753(w)
+

Mass (m/z) : EI+ (70eV). 437([M] , 7%), 354(14%), 339(7%),


311(16%), 283(8%), 282(4%) , 254(4%), 166(7%), 136(11%), 98(100%),
55(17%)

- 87 -

1H NMR (500MHz, DMSO-d6) :

0.93(3H, t, J = 7.4 Hz, H-13),

1.34(3H, t, J = 7.0 Hz, H-21), 1.37(2H, m, H-27), 1.48(4H, m, H-26,


28), 1.74(2H, m, H-12), 2.44(4H, br m, H-25, 29), 2.78(2H, t, J = 7.6
Hz, H-11), 3.69(2H, s, H-23), 4.16(3H, s, H-10), 4.20(2H, q, J = 7.0
Hz, H-20), 7.23(1H, d, J = 8.9 Hz, H-18), 8.16(1H, dd, J = 8.8, 2.2
Hz, H-17), 8.33(1H, d, J = 2.2 Hz, H-15), 12.03(1H, br s, NH)

13

C NMR (125MHz, DMSO-d6) : 14.0(C-13), 14.5(C-21), 22.0(C-12),

23.8(C-27), 25.7(C-26, 28), 27.4(C-11), 38.1(C-10), 54.3(C-25, 29),


64.8(C-20), 65.5(C-23), 112.6(C-18), 122.9(C-16), 124.6(C-9),
128.6(C-14), 131.6(C-15), 132.8(C-17), 138.2(C-8), 145.2(C-1),
149.2(C-6), 153.9(C-4), 160.4(C-19), 195.8(C-22)
Elemental Analysis (%) : 16.01(N), 65.82(C), 7.12(H), 0.05(S)
HPLC Chromatogram of Piperidinohongdenafil
Chrom Ttpe : Fixed WL Chromatogram, 291 nm

- 88 -

UV Spectrum of Piperidinohongdenafil

RT 26.08 min (S) Current Spectrum

IR Spectrum of Piperidinohongdenafil

- 89 -

Mass Spectrum of Piperidinohongdenafil (EI+)

[M]+

- 90 -

Theoretical Ion Distribution of Piperidinohongdenafil (EI+)


Molecular Formula : C24 H31 N5 O3
(m/z 437.2427, MW 437.5418, U.S. 12.0)
Base Peak : 437.2427, Averaged MW : 437.5437 (a), 437.5444 (w)
m/z
437.2427
438.2457
439.2485
440.2511
441.2537
442.2563
443.2588

INT.
100.0000 **********************************************************
29.1097 *****************
4.6864 ***
0.5429
0.0496
0.0037
0.0002

Elemental Composition of Piperidinohongdenafil (EI+)


Observed m/z
437.2441

Int%
98.1

Err[ppm
-9.0
+6.3
+0.2
-6.0
+9.4
+3.2
-10.2
-2.9
+6.3
-7.1
+2.1
-1.4
-7.5
+1.7
-4.5
-10.6
+10.9
+4.7
-1.4
+7.8

/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/

mmu]
-3.9
+2.8
+0.1
-2.6
+4.1
+1.4
-4.5
-1.3
+2.8
-3.1
+0.9
-0.6
-3.3
+0.7
-2.0
-4.6
+4.8
+2.1
-0.6
+3.4

- 91 -

Unsaturation
15.5
7.0
11.5
16.0
7.5
12.0
3.0
16.5
12.5
3.5
-0.5
3.0
7.5
3.5
8.0
12.5
-0.5
4.0
8.5
4.5

Composition
C 31 H 33 O 2
C 23 H 35 O 7 N
C 26 H 33 O 4 N 2
C 29 H 31 O N 3
C 21 H 33 O 6 N 4
C 24 H 31 O 3 N 5
C 17 H 35 O 8 N 5
C 27 H 29 N 6
C 22 H 29 O 2 N 8
C 15 H 33 O 7 N 8
C 10 H 33 O 9 N 10
C 20 H 39 O 7 N S
C 23 H 37 O 4 N 2 S
C 18 H 37 O 6 N 4 S
C 21 H 35 O 3 N 5 S
C 24 H 33 N 6 S
C 13 H 37 O 8 N 6 S
C 16 H 35 O 5 N 7 S
C 19 H 33 O 2 N 8 S
C 14 H 33 O 4 N 10 S

1H-NMR

Spectrum of Piperidinohongdenafil(500MHz, DMSO)

O
26
27

25

28
29

23

22

HN

13
21

15

16

10

10

14

19

17

20

18

12

26,28

11
13

21

11
20

15

18

23

25,29 27

12

17
5

13C-NMR

Spectrum of Piperidinohongdenafil(125MHz, DMSO)

O
26
27

25

28
29

10

23

22

16

HN

15
14

19

17

18

12
11

20

21

13

25,29

19 4
1
6

15
17 14 9

18
16

22

- 92 -

20
23

26,28
12
13
10 11
21
27

Pseudovardenafil

/ : Pseudovardenafil / Piperidenafil
/ : C22H29N5O4S / 459.57
: 1-[[3-(1,4-dihydro-5-methyl-4-oxo-7-propylimidazo[5,1-f][1,2,4]triazin-2-yl)-4-ethoxyphenyl]sulfonyl]piperidine
O

HN
N


HPLC RT (min) : 21.6
UV max (nm) : 218.1
IR (cm-1) : (CHCl3). 2938(m), 1697(s), 1624(m), 1472(m), 1339(w),
1281(w), 1167(m), 1111(w), 1034(w), 931(w), 755(w)
Mass (m/z) : FAB+ (m-NBA). 482([M+Na]+, 5%), 460([M+H]+, 100%),
431(7%), 312(8%), 283(4%), 151(8%), 84(8%)

- 93 -

1H NMR (400 MHz, DMSO-d6) : 0.92(3H, t, J = 7.4 Hz, H-13),


1.32(3H, t, J = 7.0 Hz, H-21), 1.36(2H, br m, H-26), 1.53(4H, br m,
H-25,27), 1.73(2H, m, H-12), 2.48(3H, s, H-10), 2.82(2H, t, J = 7.5
Hz, H-11), 2.90(4H, br m, H-24,28), 4.20(2H, q, J = 7.0 Hz, H-20),
7.37(1H, d, J = 8.8 Hz, H-18), 7.86(2H, m, H-15,17), 11.69(1H, br s,
NH)

13

C NMR (100 MHz, DMSO-d6) : 13.7(C-21), 14.2(C-10), 14.3(C-13),

20.2(C-12), 22.9(C-26), 24.6(C-25,27), 27.2(C-11), 46.6(C-24,28),


64.9(C-20), 113.2(C-18), 113.7(C-9), 120.7(C-16), 127.0(C-14),
129.9(C-15), 131.9(C-17), 137.6(C-3), 144.4(C-1), 146.1(C-6),
155.1(C-4), 160.1(C-19)
Elemental Analysis (%) : 57.58(C), 6.34(H), 15.26(N), 7.02(S)
HPLC Chromatogram of Pseudovardenafil

- 94 -

UV Spectrum of Pseudovardenafil

IR spectrum of Pseudovardenafil

- 95 -

Mass spectrum of Pseudovardenafil(FAB+)

[M+H]+

Theoretical Ion Distribution of Pseudovardenafil (FAB+)


Molecular Formula : C22 H30 O4 N5 S
(m/z 460.2019, MW 460.5773, U.S. 11.5)
Base Peak : 460.2019, Averaged MW : 460.5773 (a), 460.5783 (w)
m/z
460.2019
461.2047
462.2025
463.2035
464.2045
465.2059
466.2075
467.2092

INT.
100.0000
27.6976
8.9257
1.7297
0.2622
0.0321
0.0033
0.0003

**********************************************************
****************
*****
*

Elemental Composition of Pseudovardenafil (FAB+)


Observed m/z
460.2019

Int%
100.0

Err[ppm
-1.4
-5.4
+1.6
-2.5
+0.0
+3.0
-2.9
-1.5
+1.5
-4.4
+4.4

/
/
/
/
/
/
/
/
/
/
/
/

mmu]
-0.6
-2.5
+0.7
-1.1
+0.0
+1.4
-1.3
-0.7
+0.7
-2.0
+2.0

- 96 -

Unsaturation
19.5
6.5
20.0
7.0
11.5
12.0
16.5
3.0
3.5
8.0
4.0

Composition
C 30 H 26 O 2 N 3
C 18 H 26 O 4 N 5
C 28 H 24 O N 6
C 16 H 28 O 8 N 8
C 22 H 30 O 4 N 5 S
C 20 H 28 O 3 N 8 S
C 23 H 26 N 9 S
C 16 H 36 O 7 N 4 S 2
C 14 H 34 O 6 N 7 S 2
C 17 H 32 O 3 N 8 S 2
C 12 H 32 O 5 N 10 S 2

1H-NMR

spectrum of Pseudovardenafil (400MHz, DMSO)

10

24
25

HN

15

S
N

26

20

18

27

21

13

14

17

28

10

15,17

12

11
21

13

11
20

24
28

25
27
12

18
26
5

13C-NMR

spectrum of Pseudovardenafil (100MHz, DMSO)

10

24
25

HN

14

26

18

27

17

28

3
N

15

20

11
21

12

13

24,28

25,27
12

11

19

20

18

15 14

26

17
16

- 97 -

10
13

21

Thiosildenafil

: Thiosildenafil
/ : C20H30N6O3S2 / 490.64
: 5-[2-Ethoxy-5-(4-methylpiperazine-1-sulfonyl)phenyl]-1methyl-3-propyl-1,6-dihydropyrazolo [4,3-d]pyrimidin-7thione
S

HN

S
N

N
N
O


HPLC RT (min) : 37.14
UV max (nm) : 353.30
IR (cm-1) : (CHCl3). 3278(w), 2938(w), 2800(w), 1546(m),
1502(m), 1457(m), 1349(m), 1255(m), 1160(s), 941(w), 740(w)
Mass (m/z) : EI+ (70eV). 490([M]+, 70%), 420(70%), 397(12%),
384(5%), 327(38%), 312(4%) , 299(34%), 298(12%), 269(9%), 228(5%),
99(100%), 56(79%)
- 98 -

1H NMR (500MHz, CDCl3) : 1.06(3H, t, J = 7.4 Hz, H-13), 1.72(3H,


t, J = 6.9 Hz, H-21), 1.85(2H, m, H-12), 2.27(3H, s, H-29), 2.50(4H,
br m, H-25, 27), 2.94(2H, t, J = 7.5 Hz, H-11), 3.11(4H, br m, H-24,
28), 4.39(2H, q, J = 6.9 Hz, H-20), 4.52(3H, s, H-10), 7.17(1H, d, J =
8.8 Hz, H-18), 7.85(1H, dd, J = 8.8, 2.3 Hz, H-17), 8.85(1H, d, J =
2.3 Hz, H-15), 12.39(1H, br s, NH)

13

C NMR (125MHz, CDCl3) : 14.0(C-13), 14.6(C-21), 22.1(C-12),

27.6(C-11), 39.4(C-10), 45.7(C-29), 45.9(C-24, 28), 54.0(C-25, 27),


66.4(C-20), 113.1(C-18), 119.8(C-16), 129.2(C-14), 130.8(C-15),
132.0(C-17), 132.3(C-9), 133.9(C-8), 146.0(C-6), 146.5(C-1),
159.4(C-19), 171.8(C-4)
Elemental Analysis (%) : 17.12(N), 53.34(C), 6.23(H), 13.84(S)

HPLC Chromatogram of Thiosildenafil


Chrom Ttpe : Fixed WL Chromatogram, 223 nm

- 99 -

UV Spectrum of Thiosildenafil

RT 37.14 min (S) Current Spectrum

IR Spectrum of Thiosildenafil

- 100 -

Mass Spectrum of Thiosildenafil (EI+)

[M]+

- 101 -

Theoretical Ion Distribution of Thiosildenafil (EI+)


Molecular Formula : C22 H30 N6 O4 S2
(m/z 490.1821, MW 490.6506, U.S. 13.0)
Base Peak : 490.1821, Averaged MW : 490.6491 (a), 490.6504 (w)
m/z
490.1821
491.1848
492.1811
493.1823
494.1807
495.1811
496.1813
497.1820
498.1828

INT.
100.0000
28.8162
13.4682
3.0143
0.6753
0.1129
0.0161
0.0019
0.0002

**********************************************************
*****************
********
**

Elemental Composition of Thiosildenafil (EI+)


Observed m/z
490.1808

Int%
100.0

Err[ppm
+5.6
-6.4
-3.7
-9.1
-0.9
-6.4
+7.3
+1.8
-3.7
-1.3
+6.9
+1.4
+9.6
+4.2
-7.8
+0.4
+6.9
-5.1
-8.2
+5.5
+0.0
-5.4
+8.2
+2.8
-2.7
-8.2
+5.5
-6.5
+0.0

/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/

mmu]
+2.7
-3.1
-1.8
-4.5
-0.5
-3.1
+3.6
+0.9
-1.8
-0.6
+3.4
+0.7
+4.7
+2.0
-3.8
+0.2
+3.4
-2.5
-4.0
+2.7
+0.0
-2.7
+4.0
+1.4
-1.3
-4.0
+2.7
-3.2
+0.0

- 102 -

Unsaturation
20.0
11.0
11.5
16.0
12.0
16.5
8.0
12.5
17.0
16.0
12.0
16.5
12.5
17.0
8.0
4.0
17.5
8.5
12.0
3.5
8.0
12.5
4.0
8.5
13.0
17.5
9.0
0.0
13.5

Composition
C 32 H 26 O 5
C 25 H 30 O 10
C 23 H 28 O 9 N 3
C 26 H 26 O 6 N 4
C 21 H 26 O 8 N 6
C 24 H 24 O 5 N 7
C 16 H 26 O 10 N 8
C 19 H 24 O 7 N 9
C 22 H 22 O 4 N 10
C 29 H 30 O 5 S
C 24 H 30 O 7 N 2 S
C 27 H 28 O 4 N 3 S
C 22 H 28 O 6 N 5 S
C 25 H 26 O 3 N 6 S
C 18 H 30 O 8 N 6 S
C 13 H 30 O 10 N 8 S
C 23 H 24 O 2 N 9 S
C 16 H 28 O 7 N 9 S
C 26 H 34 O 5 S 2
C 18 H 36 O 10 N S 2
C 21 H 34 O 7 N 2 S 2
C 24 H 32 O 4 N 3 S 2
C 16 H 34 O 9 N 4 S 2
C 19 H 32 O 6 N 5 S 2
C 22 H 30 O 3 N 6 S 2
C 25 H 28 N 7 S 2
C 17 H 30 O 5 N 8 S 2
C 10 H 34 O 10 N 8 S 2
C 20 H 28 O 2 N 9 S 2

1H-NMR

Spectrum of Thiosildenafil (500MHz, CDCl3)

10

4
O
24

14

25
N
29

15

28

1
12

11
20

18

27

N2
8

19

17

10

HN

13

13

21

25,27
15
5

13C-NMR

24,28

11

21

12

Spectrum of Thiosildenafil (125MHz, CDCl3)

10

4
O
24

15

28

HN

25

29

20

18

17

29

N2
14

19

17
18

27

11
20

12
13

21

25,27
9
4

19

15

17

14

16

18

- 103 -

20

24,28
29

10

11

12
21

13

Xanthoanthrafil

/ : Xanthoanthrafil / Benzamidenafil
/ : C19H23N3O6 / 389.40
: N-(3,4-dimethoxybenzyl)-2-{[(1R)-2-hydroxy-1-methylethyl]amino}-5-nitrobenzamide
OH
HN

O
N
H
OCH3
OCH3

NO2


HPLC RT (min) : 37.30
UV max (nm) : 377.42
IR (cm-1) : (CHCl3). 3347(w), 2935(w), 1636(m), 1589(m), 1516(s),
1463(w), 1325(s), 1277(s), 1026(w), 818(w), 750(w)
+

Mass (m/z) : EI+ (70eV). 389([M] , 27%), 358(42%), 220(4%),


191(24%), 152(75%), 151(100%) , 107(20%), 106(15%), 90(11%), 65(6%)

- 104 -

1H NMR (500MHz, DMSO-d6) : 1.17(3H, d, J = 8.1 Hz, H-21),


3.46(2H, m, H-22), 3.73(1H, m, H-20), 3.75(3H, s, H-8), 3.78(3H, s,
H-7), 4.37(2H, m, H-9), 6.83(1H, m, H-10), 6.86(1H, d, J = 9.4 Hz,
H-16), 6.89(1H, d, J = 7.8 Hz, H-6), 6.92(1H, s, H-3), 6.96(1H, d, J =
7.8 Hz, H-5), 8.11(1H, dd, J = 9.4, 2.6 Hz, H-15), 8.58(1H, d, J =
2.6 Hz, H-13), 9.08(1H, d, J = 7.8 Hz, H-19)

13

C NMR (125MHz, DMSO-d6) : 16.9(C-21), 42.2(C-9), 49.3(C-20),

55.5(C-7, 8), 64.1(C-22), 111.2(C-16), 111.6(C-3), 111.8(C-6),


113.1(C-12), 119.5(C-5), 125.7(C-13), 128.0(C-15), 131.7(C-4),
134.2(C-14), 147.9(C-1), 148.6(C-2), 153.5(C-17), 167.4(C-11)
Elemental Analysis (%) : 10.83(N), 58.70(C), 6.00(H), 0(S)

HPLC Chromatogram of Xanthoanthrafil


Chrom Ttpe : Fixed WL Chromatogram, 223 nm

- 105 -

UV Spectrum of Xanthoanthrafil

RT 37.30 min (S) Current Spectrum

IR Spectrum of Xanthoanthrafil

- 106 -

Mass Spectrum of Xanthoanthrafil (EI+)

[M]+

Theoretical Ion Distribution of Xanthoanthrafil (EI+)


Molecular Formula : C19 H23 N3 O6
(m/z 389.1587, MW 389.4081, U.S. 10.0)
Base Peak : 389.1587, Averaged MW : 389.4091 (a), 389.4098 (w)
m/z
389.1587
390.1618
391.1642
392.1668
393.1692
394.1716
395.1741

INT.
100.0000 **********************************************************
22.8081 *************
3.6843 **
0.4452
0.0442
0.0037
0.0003

Elemental Composition of Xanthoanthrafil (EI+)


Observed m/z
389.1592

Int%
56.9

Err[ppm
-2.2
-9.1
+8.2
+1.3
-5.6
-12.5
+11.6
+4.7
-10.4
-2.2
+8.2
-6.9
+1.3

/
/
/
/
/
/
/
/
/
/
/
/
/
/

mmu]
-0.8
-3.5
+3.2
+0.5
-2.2
-4.9
+4.5
+1.8
-4.0
-0.8
+3.2
-2.7
+0.5

- 107 -

Unsaturation
9.5
14.0
5.5
10.0
14.5
19.0
6.0
10.5
1.5
15.0
11.0
2.0
15.5

Composition
C 21 H 25 O 7
C 24 H 23 O 4 N
C 16 H 25 O 9 N 2
C 19 H 23 O 6 N 3
C 22 H 21 O 3 N 4
C 25 H 19 N 5
C 14 H 23 O 8 N 5
C 17 H 21 O 5 N 6
C 10 H 25 O 10 N 6
C 20 H 19 O 2 N 7
C 15 H 19 O 4 N 9
C 8 H 23 O 9 N 9
C 18 H 17 O N 10

1H-NMR

Spectrum of Xanthoanthrafil (500MHz, DMSO)

21
20
HN 19

7,8,20

OH
22
O
5

17

12

16

11

N
H 10

OCH 3
7
3

13

13C-NMR

OCH 3
8

14
18
NO 2

15

19

13

15

6
9

16

22

10

Spectrum of Xanthoanthrafil (125MHz, DMSO)

21
20
HN 19
17
16

OH
22
O
11

N10
H

6
1

13

15

9
12

14
18
NO2

OCH3
8

OCH3
7

11

17 2

4 15 13
14
12

7,8

3
6
16

- 108 -

22

21
20 9

Desmethylsibutramine

: Desmethylsibutramine
/ : C16H24ClN / 265.84
: {1-[1-(4-Chloro-phenyl)-cyclobutyl]-3-methyl-butyl}methyl-amine

HN
Cl


HPLC RT (min) : 34.61
UV max (nm) : 222.71
-1

IR (cm ) : (CHCl3). 3408(w), 2958(s), 2731(w), 1591(w),


1493(m), 1466(m), 1415(w), 1095(w), 1012(w), 753(w)
Mass (m/z) : FAB+ (m-NBA). 289([M+Na]+, 7%), 266([M+H]+, 100%),
176(9%), 165(5%)

- 109 -

H NMR (400MHz, DMSO-d6) : 0.85(6H, m, H-1, 2), 1.12(1H, m,


H-4), 1.25(1H, m, H-4), 1.58(1H, m, H-3), 1.71(1H, m, H-10), 1.94(1H,
m, H-10), 2.30-2.61(4H, m, H-9, 11), 2.55(3H, s, H-7), 3.44(1H, m,
H-5), 7.42(2H, d, J = 8.4 Hz, H-13, 17), 7.48(2H, d, J = 8.4 Hz,
H-14, 16), 8.38(1H, br s, H-6), 8.66(1H, br s, H-6)

13

C NMR (100MHz, DMSO-d6) : 15.1(C-10), 21.6, 22.7(C-1, 2),

25.2(C-3), 31.8, 32.2(C-9, 11), 33.0(C-7), 36.6(C-4), 49.0(C-8),


63.9(C-5), 128.0(C-14, 16), 129.8(C-13, 17), 131.4(C-12), 141.7(C-15)
Elemental Analysis (%) : 4.62(N), 63.49(C), 8.50(H), 0(S)

HPLC Chromatogram of Desmethylsibutramine


Chrom Ttpe : Fixed WL Chromatogram, 291 nm

- 110 -

UV Spectrum of Desmethylsibutramine

RT

34.61 min (S) Current Spectrum

IR Spectrum of Desmethylsibutramine

- 111 -

Theoretical Ion Distribution of Desmethylsibutramine (FAB+)


Molecular Formula : C16 H25 Cl N
(m/z 266.1676, MW 266.8342, U.S. 4.5)
Base Peak : 266.1676, Averaged MW : 266.8355 (a), 266.8389 (w)
m/z
266.1676
267.1708
268.1651
269.1680
270.1712
271.1745
272.1778

INT.
100.0000
18.5382
33.5970
6.0166
0.5210
0.0284
0.0011

**********************************************************
***********
*******************
***

Elemental Composition of Desmethylsibutramine (FAB+)


Observed m/z
266.1682

Int%
100.0

Err[ppm / mmu]
+9.5 / +2.5
+2.6 / +0.7

- 112 -

Unsaturation
9.5
4.5

Composition
C 17 H 20 N 3
C 16 H 25 N 35 Cl

1H-NMR

Spectrum of Desmethylsibutramine (400MHz, DMSO)

10
11

9
17
16

Cl

15

14

12

1,2

HN

13

1
3

14,16 13,17

5
6

13C-NMR

9,11
9,11

10 10 3 4

Spectrum of Desmethylsibutramine (100MHz, DMSO)

10
11

9
17
16

Cl

15

14

12

13

1
3
2

HN
7

9/11
13,17 14,16
5

15 12

- 113 -

47

1/2

10

N-nitrosofenfluramine

: N-nitrosofenfluramine
/ : C12H15F3N2O / 260.26

N
N


HPLC RT (min) : 41.22
UV max (nm) : 233.22
IR (cm-1) : (CHCl3). 2981(w), 2940(w), 1448(w), 1330(s),
1164(m), 1124(s), 1074(m), 914(w), 803(w), 704(w)
Mass (m/z) : FAB+ (m-NBA). 283([M+Na]+, 10%), 261([M+H]+,
100%), 260(7%), 230(7%), 187(26%), 186(20%), 159(44%), 154(7%),
137(7%), 101(30%), 70(11%), 56(5%)

- 114 -

1H NMR (400MHz, DMSO-d6) : 0.87(3H, t, J = 7.2 Hz, H-5)


1.42(3H, d, J = 6.8 Hz, H-3) 3.17(2H, m, H-1), 3.41(1H, m, H-4)
3.51(1H, m, H-4')

4.84(1H, m, H-2)

7.52(2H, m, H-10, 11), 7.57(2H,

m, H-7, 9)

13

C NMR (100MHz, DMSO-d6) : 11.4(C-5), 19.5(C-3), 37.4(C-4),

39.9(C-1), 59.9(C-2), 123.1(C-9), 125.6(C-7, 12), 129.2(C-8, 10),


133.3(C-11), 139.5(C-6)
Elemental Analysis (%) : 10.82(N), 55.32(C), 5.83(H), 0(S)

HPLC Chromatogram of N-nitrosofenfluramine


Chrom Ttpe : Fixed WL Chromatogram, 223 nm

- 115 -

UV Spectrum of N-nitrosofenfluramine

RT 41.22 min (S) Current Spectrum

IR Spectrum of N-nitrosofenfluramine

- 116 -

Molecular Formula : C12 H16 F3 N2 O


(m/z 261.1215, MW 261.2670, U.S. 4.5)
Base Peak : 261.1215, Averaged MW : 261.2680 (a), 261.2686 (w)
m/z
261.1215
262.1246
263.1273
264.1299
265.1325

INT.
100.0000 **********************************************************
14.3596 ********
1.1559 *
0.0678
0.0030

Elemental Composition of N-nitrosofenfluramine (FAB+)


Observed m/z
261.1219

Int%
100.0

Err[ppm
-7.9
-12.3
+16.1
+5.8
-16.6
+11.7
+1.5

/
/
/
/
/
/
/
/

mmu]
-2.1
-3.2
+4.2
+1.5
-4.3
+3.1
+0.4

Unsaturation
7.5
3.5
4.0
8.5
-0.5
0.0
4.5

- 117 -

Composition
C 14 H 17 O 3 N 2
C 11 H 18 O 4 N 2 F
C 12 H 17 O 3 N F 2
C 15 H 15 N 2 F 2
C 8 H 19 O 5 N 2 F 2
C 9 H 18 O 4 N F 3
C 12 H 16 O N 2 F 3

1H-NMR

Spectrum of N-nitrosofenfluramine(400MHz, DMSO)

3
5

10,11

F
12

F
11

N
N
O

10

7,9
44
2

- 118 -



Instrumental Analysis Data of Illegal
Compounds in Food
2009 6
2009 6


, , , , ,
, , , ,
(), ()


122-704 194
02-380-1674~5, 02-355-6037
National Institute of Food and Drug Safety
Evaluation
194 Tongilro Eunpyeong-gu Seoul 122-704,
Korea
Tel 82-2-380-1674, Fax 82-2-355-6037
Web site : http//www.nifds.go.kr