Arch. Pharm. Chem. Life Sci. 2012, 000, 1–7
Heterocyclic Sulfamoyl-phenyl-carboximidamides from Clinically Applied Sulfonamides
5
–
1585, 1537 (n C C), 1141 (n SO ), 1086, 936 (d C–H), 858, 650 (g C–H),
–
2
6-methoxypyrazine-2-carbimidate (5) was obtained according to
the method described earlier by Foks and Manowska [26]. Reaction
yield and compound characteristics were found to be identical
with those described (mp 100–1018C).
573 (g N–H) cmꢂ1 1H NMR (200 MHz, DMSO-d6): d 6.80 (d, 1H,
;
J ¼ 4.4 Hz), 6.83 (br s, 2H, NH2 þ D2O exchangeable), 7.00 (d, 2H,
J ¼ 8.5 Hz), 7.24 (d, 1H, J ¼ 4.7 Hz), 7.53–7.60 (m, 1H), 7.74 (d, 2H,
J ¼ 8.5 Hz), 7.91–8.00 (m, 1H), 8.27 (d, 1H, J ¼ 8.0 Hz), 8.63 (d, 1H,
J ¼ 4.8 Hz), 11.50 (br s, 1H, NH þ D2O exchangeable); 13C NMR
(200 MHz, DMSO-d6): d 108.08, 121.76, 121.91 (2C), 125.88, 126.38,
127.52 (2C), 136.51, 137.52, 148.38, 151.36, 152.34, 153.93, 169.02.
Anal. Calcd for C15H13N5O2S2 (mw 359.43): C, 50.12; H, 3.65;
N, 19.48. Found: C, 49.99; H, 3.66; N, 19.51.
Synthesis of methyl pyrazine-2-carbimidate (4)
Pyrazine-2-carbonitrile (10 mL, 116 mmol) was dissolved in
20 mL of methanol and 1 mL (6.5 mmol) of DBU was added to
the solution. The mixture was stirred for 1 min and the product
precipitated abundantly. The mixture was cooled and the pre-
cipitate was filtered off and recrystallized from methanol yield-
ing 13.5 g (85%) of colorless needles; mp 115–1168C [25].
4-Chloro-N-[4-(thiazol-2-sulfamoyl)phenyl]pyridine-2-
carboximidamide (9)
This compound was recrystallized from dioxane. Yield 75%, mp
–
General method for the synthesis of
sulfamoylphenylcarbimidamides (6–13)
247–2498C; IR (KBr): 3459, 3352 (n N–H), 1655 (n C N), 1534, 1423
–
ꢂ1
–
(n C C), 1284, 1150 (n SO ), 1087, 937 (d C–H), 573 (g N–H) cm
;
–
2
Appropriate carbonitrile 1–3 (5 mmol) was dissolved in 10 mL of
methanol and 0.1 mL (0.7 mmol) of DBU was added. The mixture
was refluxed for 0.5 h required for methyl carbimidate for-
mation. Then 4.5 mmol of appropriate sulfonamide was added.
The mixture was refluxed for another 3 h. The solvent was
evaporated and 20 g of ice was added. The precipitate was filtered
off and recrystallized from a suitable solvent.
1H NMR (500 MHz, DMSO-d6): d 6.81 (d, 1H, J ¼ 4.4 Hz), 6.85 (br s,
2H, NH2 þ D2O exchangeable), 7.05 (d, 2H, J ¼ 7.3 Hz), 7.24
(d, 1H, J ¼ 4.4 Hz), 7.71–7.77 (m, 3H), 8.27 (d, 1H, J ¼ 2.0 Hz),
8.63 (d, 1H, J ¼ 5.3 Hz), 12.6) (br s, 1H, NH þ D2O exchangeable);
13C NMR (500 MHz, DMSO-d6): d 108.21, 121.70, 122.01 (2C),
124.86, 125.82, 127.52 (2C), 136.31, 144.17, 150.00, 151.41,
153.30, 168.92. Anal. Calcd for C15H12ClN5O2S2 (mw 393.88): C,
45.74; H, 3.07; N, 17.78. Found: C, 45.63; H, 3.07; N, 17.75.
N-[4-(4-Methylpyrimidin-2-sulfamoyl)phenyl]pyridine-2-
carboximidamide (6)
N-[4-(4-Methylpyrimidin-2-sulfamoyl)phenyl]pyrimidine-2-
carboximidamide (10)
This compound was recrystallized from ethylene glycol–ethanol
The crude product was recrystallized from ethylene glycol–
ethanol mixture (1:1). Yield 45%, mp 218–2208C; IR (KBr):
–
3467, 3356 (n N–H), 3037, 2852 (n C–H), 1648 (n C N), 1568
–
–
(n C C), 1330, 1157 (n SO ), 1090 (d C–H), 894 (g C–H), 573
mixture (1:1). Yield 41%, mp 207–2088C; IR (KBr): 3342, 3262
–
2
–
–
–
(n N–H), 1644 (n C N), 1594, 1565, 1498 (n C C), 1405, 1335,
–
(g N–H) cmꢂ1 1H NMR (200 MHz, DMSO-d6): d 2.34 (s, 3H CH3),
;
1161 (n SO2), 1090 (d C–H), 809 (g C–H), 585 (g N–H) cmꢂ1; 1H NMR
(200 MHz, DMSO-d6): d 2.33 (s, 3H, CH3), 6.88 (d, 1H, J ¼ 4.9 Hz),
7.43 (br s, 2H, NH2 þ D2O exchangable), 7.56–7.79 (m, 2H), 7.84–
8.09 (m, 3H), 8.33 (d, 1H, J ¼ 4.9 Hz), 8.98–9.06 (m, 2H), 11.50
(br s, 1H, NH þ D2O exchangable); 13C NMR (200 MHz, DMSO-d6):
d 23.58, 112.72, 115.06, 119.87, 122.65 (2C), 129.32 (2C), 131.25,
133.22, 153.75, 157.09, 157.86, 157.99 (2C), 168.40. Anal. Calcd
for C16H15N7O2S (mw 369.40): C, 52.02; H, 4.09; N, 26.54. Found:
C, 52.11; H, 4.08; N, 26.59.
6.80 (br s, 2H, NH2 þ D2O exchangeable), 6.92 (d, 1H, J ¼ 5.0 Hz),
7.00 (d, 2H, J ¼ 8.3 Hz), 7.53–7.59 (m, 1H), 7.93–7.97 (m, 3H),
8.25 (d, 1H, J ¼ 8.0 Hz), 8.35 (d, 1H, J ¼ 5.0 Hz), 8.63 (d, 1H,
J ¼ 4.4 Hz), 11.50 (br s, 1H, NH þ D2O exchangeable); 13C NMR
(200 MHz, DMSO-d6): d 23.62, 115.13, 121.73 (2C), 125.92, 129.71
(2C), 133.64, 137.54, 148.40 (2C), 151.29, 152.41, 155.02, 157.08,
157.90, 168.44. Anal. Calcd for C17H16N6O2S (mw 368.41): C,
55.42; H, 4.38; N, 22.81. Found: C, 55.53; H, 4.37; N, 22.76.
N-[4-(6-Methoxypyridazin-3-sulfamoyl)phenyl]pyridine-2-
carboximidamide (7)
This compound was recrystallized from ethylene glycol–ethanol
N-[4-(4,6-Dimethylpyrimidin-2-sulfamoyl)phenyl]-
pyrimidine-2-carboximidamide (11)
This compound was recrystallized from dioxane. Yield 65%, mp
mixture (1:1). Yield 58%, mp 176–1788C; IR (KBr): 3478,
268–2718C; IR (KBr): 3334 (n N–H), 3108, 2923 (n C–H), 1693, 1598
–
–
–
3347, 3280 (n N–H), 1640 (n C N), 1572 (n C C), 1332 (n SO ),
–
–
–
–
2
(n C N), 1569, 1520 (n C C), 1399, 1320, 1159 (n SO ), 680 (g C–H),
–
2
1297, 1137 (n SO2), 1083, 931 (d C–H), 572 (g N–H) cmꢂ1; 1H NMR
(200 MHz, DMSO-d6): d 3.85 (s, 3H OCH3), 6.58 (br s, 2H,
NH2 þ D2O exchangeable), 7.00 (d, 2H, J ¼ 8.2 Hz), 7.30 (d, 1H,
J ¼ 9.7 Hz), 7.53–7.59 (m, 1H), 7.74–7.81 (m, 3H), 7.91–7.99
(m, 1H), 8.20 (d, 1H, J ¼ 8.0 Hz), 8.63 (d, 1H, J ¼ 4.4 Hz), 11.50
(br s, 1H, NH þ D2O exchangeable); 13C NMR (200 MHz, DMSO-
d6): d 54.74, 121.77, 122.14 (2C), 124.83, 125.91, 126.27, 127.97
(2C), 135.88, 137.53, 148.38, 151.31, 152.43, 153.12, 154.33,
158.90. Anal. Calcd for C17H16N6O3S (mw 384.41): C, 53.12; H,
4.20; N, 21.86. Found: C, 53.06; H, 4.21; N, 21.97.
589 (g N–H) cmꢂ1
;
1H NMR (200 MHz, DMSO-d6): d 2.23 (s, 6H,
2CH3), 6.30 (br s, 2H, NH2 þ D2O exchangable), 6.72 (s, 1H), 7.76
(t, 1H, J ¼ 4.8 Hz), 7.95–8.06 (m, 4H), 9.00 (d, 2H, J ¼ 5.0 Hz),
11.60 (br s, 1H, NH þ D2O exchangable); 13C NMR (200 MHz,
DMSO-d6): d 23.13 (2C), 113.68, 119.66, 123.67 (2C), 129.36 (2C),
135.96, 142.17, 156.56 (2C), 158.19, 161.71, 167.61 (2C), 169.27.
Anal. Calcd for C17H17N7O2S (mw 383.43): C, 53.25; H, 4.47;
N, 25.57. Found: C, 53.12; H, 4.46; N, 25.51.
N-[4-(6-Methoxypyridazin-3-sulfamoyl)phenyl]pyrimidine-
2-carboximidamide (12)
N-[4-(Thiazol-2-sulfamoyl)phenyl]pyridine-2-
carboximidamide (8)
This compound was recrystallized from dioxane–ethanol mix-
ture (1:1). Yield 53%, mp 204–2068C; IR (KBr): 3320 (n N–H), 2853
–
(n C–H), 1647 (n C N), 1586, 1564, 1529, 1469, 1414 (n C C), 1296
–
–
This compound was recrystallized from methanol. Yield 67%, mp
191–1928C; IR (KBr): 3487, 3370 (n N–H), 3108 (n C–H), 1642 (n C N),
–
(n SO2), 1266 (n C–O), 1144 (n SO2), 752 (g C–H), 576 (g N–H) cmꢂ1
;
–
–
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