150
I. Doulou et al. / European Journal of Medicinal Chemistry 80 (2014) 145e153
NMR (500 MHz, DMSO-d6)
d
2.39 (s, 3H), 7.36 (br s, 2H), 7.44 (d,
calcd for C22H39N3O3S C, 62.08; H, 9.24; N, 9.87; Found: C, 62.14; H,
9.26; N, 9.88.
J ¼ 8.3 Hz, 2H), 7.50 (d, J ¼ 7.3 Hz, 2H), 7.86 (d, J ¼ 8.3 Hz, 2H), 8.64
(d, J ¼ 7.3 Hz, 2H); 13C NMR (125 MHz, DMSO-d6)
d 21.1, 121.0, 128.3,
129.7,132.6,138.0,144.7,150.2,155.9; MS (LCeMS) (ESI,1.65 eV): m/
z positive ¼ 346 [MþNaþMeOH]þ, 314 [MþNa]þ, 292 (100%)
[MþH]þ; negative ¼ 290 [MꢁH]ꢁ, 171 (100%) [C7H7SO3]ꢁ; Elem.
Anal.: calcd for C13H13N3O3S: C, 53.60; H, 4.50; N, 14.42; Found: C,
53.75; H, 4.51; N, 14.46.
5.1.1.13. N0-((phenylsulfonyl)oxy)nicotinimidamide
(23).
Solvent: Chloroform/DMF (8/1); Reaction time: 3 h; Purification
method: recrystallization; Pale yellow crystals, yield 96%, mp 125e
127 ꢂC (ethyl acetate/ethanol); IR (KBr): 3418, 3325, 3150, 1657,
1350 & 1182 (S]O) cmꢁ1
;
1H NMR (300 MHz, CDCl3 þ DMSO-d6)
d
6.63 (br s, 2H), 7.26 (dd, J ¼ 7.9, 4.8 Hz, 1H), 7.50 (t, J ¼ 7.5 Hz, 2H),
7.60 (t, J ¼ 7.9 Hz, 1H), 7.83 (d, J ¼ 7.9 Hz, 1H), 7.94 (d, J ¼ 7.6 Hz, 2H),
5.1.1.9. N’-(4-nitrophenylsulfonyloxy)isonicotinimidamide
(19).
8.59 (d, J ¼ 3.6 Hz, 1H), 8.69 (d, J ¼ 1.4 Hz, 1H); 13C NMR (75 MHz,
Solvent: Chloroform/DMF (8/1); Reaction time: 5 h; Purification
method: recrystallization; Extraction with an additional amount of
ethyl acetate; Pale yellow crystals, yield 63%, mp 169e171 ꢂC
(ethanol); IR (KBr): 3457, 3308, 3104, 1657, 1376 & 1189 (S]O)
CDCl3 þ DMSO-d6)
d 122.2, 125.7, 127.5, 127.8, 132.7, 133.7, 135.0,
146.9, 150.5, 155.2; MS (LCeMS) (ESI, 1.65 eV): m/z positive ¼ 278
[MþH]þ, 122 [Mþ2HeC6H5SO3]þ; negative
¼
157 (100%)
[C6H5SO3]ꢁ; Elem. Anal.: calcd for C12H11N3O3S: C, 51.98; H, 4.00; N,
15.15; Found: C, 52.08; H, 4.01; N, 15.19.
cmꢁ1
;
1H NMR (300 MHz, CDCl3þDMSO-d6)
d 6.98 (br s, 2H), 7.44
(d, J ¼ 5.9 Hz, 2H), 8.18 (d, J ¼ 8.9 Hz, 2H), 8.34 (d, J ¼ 8.7 Hz, 2H),
8.54 (d, J ¼ 5.7 Hz, 2H); 13C NMR (75 MHz, CDCl3þDMSO-d6)
d 119.9,
5.1.1.14. N’-(tosyloxy)nicotinimidamide (24). Solvent: Chloroform/
DMF (8/1); Reaction time: 4 h; Purification method: recrystalliza-
tion; Pale yellow crystals, yield 98%, mp 140e142 ꢂC (ethyl acetate);
IR (KBr): 3408, 3310, 3114, 1654, 1343 & 1189 (S]O) cmꢁ1; 1H NMR
122.8, 128.9, 136.7, 140.3, 148.8, 149.4, 155.5; MS (LCeMS) (ESI,
1.65 eV): m/z positive ¼ 323 [MþH]þ, 122 (100%) [Mþ2He(O2Ne
C6H4eSO3)]þ; negative ¼ 202 (100%) [(O2NeC6H4eSO3)]ꢁ; Elem.
Anal.: calcd for C12H10N4O5S: C, 44.72; H, 3.13; N, 17.38; Found: C,
44.76; H, 3.14; N, 17.43.
(300 MHz, CDCl3 þ DMSO-d6)
d 2.37 (s, 3H), 6.47 (br s, 2H), 7.25 (dd,
J ¼ 8.1, 4.9 Hz, 1H), 7.27 (d, J ¼ 7.8 Hz, 2H), 7.82 (d, J ¼ 8.1 Hz, 2H),
7.83 (dt, J ¼ 7.2, 1.8 Hz, 1H), 8.56 (dd, J ¼ 4.8, 1.5 Hz, 1H), 8.70 (d,
5.1.1.10. N’-(propylsulfonyloxy)isonicotinimidamide
(20).
J ¼ 1.8 Hz, 1H); 13C NMR (75 MHz, CDCl3 þ DMSO-d6)
d 21.4, 123.0,
Solvent: Chloroform/DMF (8/1); Reaction time: 20 h; Purification
method: column chromatography; White crystals, yield 20%, mp
134e136 ꢂC (hexanes/ethyl acetate); IR (KBr): 3437, 3330, 3173,
126.6, 128.5, 129.3, 132.8, 134.5, 144.5, 147.9, 151.4, 155.9; MS (LCe
MS) (ESI, 1.65 eV): m/z positive ¼ 292 (100%) [MþH]þ, 122 [Mþ2He
C7H7SO3]þ; negative ¼ 171 (100%) [C7H7SO3]ꢁ; Elem. Anal.: calcd
for C13H13N3O3S: C, 53.60; H, 4.50; N, 14.42. Found: C, 53.69; H,
4.49; N, 14.45.
2967, 1665, 1352 & 1172 (S]O) cmꢁ1
;
1H NMR (300 MHz,
CDCl3 þ DMSO-d6)
d
1.02 (t, J ¼ 7.4 Hz, 3H), 1.85 (sext, J ¼ 7.6 Hz,
2H), 3.30 (t, J ¼ 7.6 Hz, 2H), 6.33 (br s, 2H), 7.56 (d, J ¼ 4.5 Hz, 2H),
8.61 (d, J ¼ 4.5 Hz, 2H); 13C NMR (75 MHz, CDCl3 þ DMSO-d6)
d 12.4,
5.1.1.15. N0-((4-nitrophenyl)sulfonyloxy)nicotinimidamide
(25).
16.7, 49.9, 120.6, 137.8, 149.8, 155.5; MS (LCeMS) (ESI, 1.65 eV): m/z
Solvent: Tetrahydrofuran; Reaction time: 1 h; Purification method:
recrystallization; Extraction with ethyl acetate instead of
dichloromethane; Baize crystals, yield 77%, mp 110e111 ꢂC (ethyl
positive
negative
¼
244 (100) [MþH]þ, 122 [Mþ2HeC3H7SO3]þ;
¼
123 (100%) [C3H7SO3]ꢁ; Elem. Anal.: calcd for
C9H13N3O3S: C, 44.43; H, 5.39; N, 17.27; Found: C, 44.56; H, 5.40; N,
17.32.
acetate), IR (KBr): 3425, 3323, 3106, 1659, 1367 & 1185 (S]O) cmꢁ1
;
1H NMR (300 MHz, CDCl3 þ DMSO-d6)
d 6.82 (br s, 2H), 7.27 (dd,
J ¼ 7.8, 4.8 Hz, 1H), 7.83 (dt, J ¼ 8.1, 1.7 Hz, 1H), 8.17 (d, J ¼ 8.9 Hz,
2H), 8.33 (d, J ¼ 8.9 Hz, 2H), 8.57 (dd, J ¼ 4.8, 1.5 Hz, 1H), 8.70 (d,
5.1.1.11. N’-(decylsulfonyloxy)isonicotinimidamide
(21). Solvent:
J ¼ 1.7 Hz, 1H); 13C NMR (75 MHz, CDCl3 þ DMSO-d6)
d 122.3, 123.0,
Chloroform/DMF (8/1); Reaction time: 20 h; Purification method:
column chromatography; White crystals, yield 15%, mp 86e88 ꢂC
(hexanes/ethyl acetate); IR (KBr): 3472, 3368, 2954, 2921, 2853,
1637, 1360 & 1174 (S]O) cmꢁ1; 1H NMR (300 MHz, CDCl3þDMSO-
125.5, 129.1, 133.8, 140.7, 146.9, 149.6, 150.7, 155.8; HRMS (ESI) Calc
C
12H11N4O5S [MþH]þ, 323.0445; found 323.0443.
d6)
d
0.79 (t, J ¼ 6.1 Hz, 3H), 1.17 (br s, 12H), 1.38 (quint, J ¼ 6.9 Hz,
5.1.1.16. N’-(propylsulfonyloxy)nicotinimidamide
(26). Solvent:
2H), 1.76 (quint, J ¼ 7.8 Hz, 2H), 3.30 (t, J ¼ 7.8 Hz, 2H), 6.56 (br s,
Chloroform; Reaction time: 20 h; Purification method: recrystalli-
zation; Pale yellow crystals, yield 93%, mp 105e106 ꢂC (hexanes/
ethyl acetate); IR (KBr): 3415, 3332, 3087, 2966, 1655, 1347 & 1197
2H), 7.58 (d, J ¼ 6.1 Hz, 2H), 8.59 (d, J ¼ 6.1 Hz, 2H); 13C NMR
(75 MHz, CDCl3þDMSO-d6)
d 13.3, 21.8, 22.5, 27.2, 28.1, 28.3, 28.4,
(S]O) cmꢁ1
;
1H NMR (300 MHz, CDCl3 þ DMSO-d6)
d 1.03 (t,
28.6, 31.0, 47.8, 120.4, 137.5, 149.4, 155.3; MS (LCeMS) (ESI, 1.65 eV):
m/z positive ¼ 342 (100%) [MþH]þ, 122 [Mþ2HeC10H21SO3]þ;
J ¼ 7.6 Hz, 3H), 1.85 (sext, J ¼ 7.6 Hz, 2H), 3.30 (t, J ¼ 7.6 Hz, 2H), 6.46
(br s, 2H), 7.31 (dd, J ¼ 7.9, 4.8 Hz, 1H), 7.98 (dt, J ¼ 7.9, 1.8 Hz, 1H),
8.62 (dd, J ¼ 4.8, 1.5 Hz, 1H), 8.88 (d, J ¼ 1.7 Hz, 1H); 13C NMR
negative
¼
221 (100%) [C10H21SO3]ꢁ; Elem. Anal.: calcd for
C
16H27N3O3S: C, 56.28; H, 7.97; N, 12.31; Found: C, 56.39; H, 7.99; N,
12.32.
(75 MHz, CDCl3 þ DMSO-d6)
d 12.2, 16.5, 49.7, 122.7, 126.1, 134.1,
147.5, 151.2, 155.6; MS (LCeMS) (ESI, 1.65 eV): m/z positive ¼ 244
5.1.1.12. N’-(hexadecylsulfonyloxy)isonicotinimidamide
(22).
[MþH]þ, 122 [Mþ2HeC3H7SO3]þ; negative
¼
123 (100%)
Solvent: Chloroform/DMF (8/1); Reaction time: 20 h; Purification
method: recrystallization; White crystals, yield 27%, mp 78e80 ꢂC
(hexanes/ethyl acetate); IR (KBr): 3469, 3365, 2953, 2921, 2847,
1637, 1359 & 1174 (S]O) cmꢁ1; 1H NMR (300 MHz, CDCl3þDMSO-
[C3H7SO3]ꢁ; Elem. Anal.: calcd for C9H13N3O3S: C, 44.43; H, 5.39; N,
17.27; Found: C, 44.51; H, 5.38; N, 17.22.
5.1.1.17. N’-(decylsulfonyloxy)nicotinimidamide (27). Solvent: Chlo-
roform; Reaction time: 20 h; Purification method: recrystallization;
Pale yellow crystals, yield 25%, mp 85e87 ꢂC (hexanes/ethyl ace-
tate); IR (KBr): 3411, 3325, 3125, 2925, 2848, 1653, 1347 & 1192 (S]
d6)
d
0.80 (t, J ¼ 6.9 Hz, 3H), 1.17 (br s, 24H), 1.38 (quint, J ¼ 7.1 Hz,
2H), 1.80 (quint, J ¼ 7.8 Hz, 2H), 3.30 (t, J ¼ 7.8 Hz, 2H), 6.35 (br s,
2H), 7.56 (d, J ¼ 5.8 Hz, 2H), 8.60 (d, J ¼ 5.9 Hz, 2H); 13C NMR
(75 MHz, CDCl3þDMSO-d6)
d
13.3, 21.8, 22.5, 27.3, 28.1, 28.39,
O) cmꢁ1
;
1H NMR (500 MHz, DMSO-d6)
d
0.83 (t, J ¼ 6.4 Hz, 3H),
28.44, 28.6, 28.7, 28.75, 28.78, 31.0, 47.9, 120.4, 137.5, 149.4, 155.3;
MS (LCeMS) (ESI, 1.65 eV): m/z positive ¼ 448.5 [MþNa]þ, 426
(100%) [MþH]þ; negative ¼ 305 (100%) [C16H33SO3]ꢁ; Elem. Anal.:
1.20 (br s, 12H), 1.39 (quint, J ¼ 7.2 Hz, 2H), 1.71 (quint, J ¼ 7.6 Hz,
2H), 3.43 (t, J ¼ 7.9 Hz, 2H), 7.33 (br s, 2H), 7.50 (dd, J ¼ 7.9, 4.8 Hz,
1H), 8.06 (dt, J ¼ 7.9,1.8 Hz,1H), 8.70 (dd, J ¼ 4.8,1.5 Hz,1H), 8.86 (d,