P. Rajender Kumar et al. / Bioorg. Med. Chem. 12 (2004) 1221–1230
1225
IR (KBr) cmꢁ1: 3258, 1714, 1676, 1620, 1492, 1427,
1230, 1049,780,725; H NMR (200 MHz, CDCl3): d 9.5
4.5. Preparation of 2-methyl-4, 5-dicarbethoxy-6-(2-the-
noyl) thieno-[3,2-b] pyrrole (4b)
1
(D2O exchangeable), 7.8 (s, 1H), 7.7 (s, 1H), 7.6 (d, 1H),
7.1 (t, 1H), 4.4 (q, 2H), 4.2 (q, 2H), 1.4 (t, 3H), 1.2 (t,
3H); M+ (m/e): 377 (97%), 331 (60%), 303 (20%), 286
(20%), 259 (15%), 248 (10%), 202 (5%), 194 (20%), 111
(75%). Anal. calcd for C17H15NO5S2: C, 54.105; H,
4.009; N, 3.713. Found: C, 54.25; H, 3.98; N, 3.68.
To the mixture of sodiumhydride (0.3 g, 12.5 mmol) and
dry dimethylformamide (30 mL), a solution of 2-methyl-
5-carbethoxy-6-(2-thenoyl)-thieno-[3,2-b]-pyrrole (4) (0.5
g, 1.56 mmol) in dimethylformamide (10 mL) was added
at 0–5 ꢀC. After 5 min, eyhylchloro formate (0.5 mL,
5.22 mmol) was added slowly with stirring. Reaction
temperature increased to 25–30 ꢀC, further contents
were stirred for 3–4 h. Upon completion of reaction, ice
water was added and adjusted the pH to 2 by addition
of HC1. Reaction mass was extracted into diethylether,
the organic layer was separated, dried (Na2SO4), filtered
and concentrated to obtain crude compound as a syr-
upy liquid. Purification by column chromatography
furnished 4b (0.55 g, 90%) as pale yellow solid; mp 95–
98 ꢀC.
4.3. Preparation of 2-chloro-5-carbethoxy-6 (2-thenoyl)
thieno [3,2-b] pyrrole (6)
2-Chloro-5-carbethoxy-thieno-[3,2-b]-pyrrole (22) (10.0
g, 42.5 mmol) was dissolved in dichloromethane (100
mL) and stannic chloride (2.05 g, 14 mmol) was added,
followed by 2-thiophenecarbonyl chloride (2.05 g,
14.07 mmol) at room temperature. The contents were
refluxed for 20 h. Reaction mixture was cooled to
room temperature, poured into ice water with stirring.
The organic layer was separated, solvent removed
under reduced pressure to obtain product as viscous oil.
This crude compound was dissolved in dichloro-
methane and triturated with petroleum ether furnished
6 (8.5 g, 55%) as pure dark greenish color low melting
solid.
IR (KBr) cmꢁ1: 3440, 1748, 1622, 1522, 1398, 1341,
1282, 1201, 1143, 1006, 834, 711; 1H NMR
(200 MHz, CDCl3): d 7.8 (d, 1H), 7.7 (d, 1H), 7.2 (t,
1H), 7.1 (s, 1H), 4.5 (q, 2H), 4.3 (q, 2H), 2.6 (s, 3H).
1.5 (t, 3H). 1.3 (t, 3H); M+ (m/e): 391 (97%), 346
(85%), 319 (20%), 273 (90%), 246 (10%), 218 (10%),
190 (8%), 111 (40%). Anal. calcd for C18H17N O5S2:
C, 55.23: H, 4.38; N, 3.58. Found: C, 55.58; H, 4.66;
N, 3.56.
IR (KBr) cmꢁ1: 3258, 1684, 1611, 1488, 1413, 1270,
1
1195, 974, 774, 721; H NMR (200 MHz, CDCl3): d 9.8
(D2O exchangeable), 7.7 (d, 1H), 7.6 (d, 1H), 7.1 (t, 1H).
6.9 (s, 1H), 4.2 (q, 2H), 1.2 (t, 3H); M+ (m/e) 339
(96%), 293 (85%), 256 (25%), 238 (8%), 210 (10%). 202
(4%), 184 (8%), 111 (30%). Anal. calcd for
C14H10NO3S2Cl: C, 49.560; H, 2.973; N, 4.130. Found:
C, 49.76; H, 2.91; N, 4.15.
4.6. Preparation of 2-methyl-5-carbethoxy-4-allyl-6-(2-
thenoyl) thieno-[3,2-b] pyrrole (4c)
To the mixture of sodiumhydride (1.2 g, 50 mmol) and
dry dimethylformamide (20 mL), a solution of 2-methyl-
5-carbethoxy-6-(2-thenoyl)-thieno-[3,2-b]-pyrrole (4) (2.0
g, 6.24 , mmol) in dimethylformamide (20 mL) was
added at 0–5 ꢀC. After 5 min, allylbromide (1.5 mL, 17.3
mmol) was added slowly with stirring. Reaction tem-
perature increased to 25–30 ꢀC. further contents were
stirred for 3–4 h. Upon completion of reaction ice water
was added and adjusted the pH to 2 by addition of HCl.
Reaction mass was extracted into diethylether, the
organic layer was separated, dried (Na2SO4), filtered
and concentrated to obtain crude compound as a syr-
upy liquid. Purification by column chromatography
furnished 4c (1.4 g, 63%) as pale yellow solid; mp 64–
66 ꢀC.
4.4. Preparation of 2-methyl-5-carbethoxy-4-carbethoxy
methyl-6-(2-thenoyl)-thieno-[3,2-b] pyrrole (4a)
To the mixture of sodiumhydride (0.2 g, 8.33 mmol) and
dry dimethylformamide (30 mL), a solution of 2-methyl-
5-carbethoxy-6-(2-thenoyl)-thieno-[3,2-b]-pyrrole (4) (0.5
g, 1.56 mmol) in dimethylformamide (10 mL) was added
at 0–5 ꢀC. After 5 min, eyhylchloroacetate (0.4 mL, 3.7
mmol) was added slowly with stirring. Reaction tem-
perature increased to 25–30 ꢀC, further contents were
stirred for 3–4 h. Upon completion of reaction ice water
was added and adjusted the pH to 2 by addition of HCl.
Reaction mass was extracted into diethylether, the
organic layer was separated, dried (Na2SO4), filtered
and concentrated to obtain crude compound as a syr-
upy liquid. Purification by column chromatography
furnished 4a (0.44 g, 70%) as pale yellow solid; mp 93–
95 ꢀC.
IR (KBr) cmꢁ1: 3104, 2981, 1712, 1638, 1519, 1493,
1
1282, 1238, 1155, 1022, 919, 795, 763, 727, 656, 556; H
NMR (200 MHz, CDCl3): d 7.7 (d, 1H), 7.6 (d, 1H), 7.1
(t, 1H), 6.7 (s, 1H), 6.0 (m, 1H), 5.1–5.2 (m, 2H), 4.0 (q,
2H), 2.6 (s, 3H), 1.0 (t, 3H). M+ (m/e): 361 (96%), 372
(45%), 344 (96%), 260 (20%), 204 (15%), 160 (10%),
111 (65%). Anal. calc for C18H17NO3S2: C, 60.156;
H, 4.771; N, 3.899. Found: C, 60.212; H, 4.66; N,
3.95.
IR (KBr) cmꢁ1: 1754, 1692, 1603, 1411, 1284, 1246,
1204, 1164, 1098, 1022, 955, 781, 501; 1H NMR
(200 MHz, CDCl3): d 7.7 (d, 1H), 7.6 (d, 1H), 7.1 (t,
1H).6.6 (s, 1H), 5.2 (s, 2H), 4.3 (q, 2H), 4.0 (q, 3H) 2.5
(s, 3H), 1.3 (t, 3H), 0.9 (t, 3H); M+ (m/e); 405 (97%),
360 (10%), 333 (15%), 286 (20%), 258 (10%), 220
(10%). 190 (30%), 111 (70%). Anal. calcd for C19H19N
O5 S2: C, 56.28; H, 4.72: N, 3.45, Found: C, 55.98; H,
4.66; N, 3.56.
4.7. Preparation of 2-methyl-5-carboxy-4-(2-propionic
acid)-6-(2-thenoyl) thieno-[3,2-b] pyrrole (4d)
2-Methyl-5-carbethoxy-4-(1-ethoxy carbonyl ethyl)-6-
(2-thenoyl) thieno-[3,2-b]-pyrrole (4g) (2.0 g, 4.94 mmol)