ethyl 4-acetyl-5-(acetyloxymethyl)-3-methyl-1H-pyrrole-2-carboxylate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of methyl pyrrole-2-carboxylate (0.222 g, 1.7 mmol) and ethyl 5-acetoxymethyl-4-acetyl-3-methylpyrrole-2-carboxylate (0.474 g, 1.7 mmol) in 1,2-dichloroethane (20 cm3) was heated under reflux and stirred with Montmorillonite clay for 7 h. The reaction was followed to completion by TLC. After the clay had been filtered off and washed well with 1,2-dichloroethane, evaporation of the combined filtrates under reduced pressure gave an oil. Chromatographic separation of an oil eluting with (5-40%) ethylacetate in hexane gave Ethyl 6-methoxycarbonyl-3,4-dimethylpyrrolo[2,3-f]indole-2-carboxylate (isomer I) as a yellow solid after crystallisation from dichloromethane-petroleum ether (0.030 g, 5.62%), m.p. 245-248° C.; δH ([2H6]-DMSO) 11.16 (1H, s, 5-NH), 11.00 (1H, s, 1-NH), 7.45 (1H, s, 8-H), 7.20 (1H, s 7-H), 4.37 (2H, q, OCH2CH3), 3.91 (3H, s, OCH3), 2.95 (3H, s, 3-CH3), 2.88 (3H, s, 4-CH3), 1.37 (3H, t, OCH2CH3); saturation of the 1-NH at δ 11.00 enhanced the signal due to 8-H at δ 7.45 (3.9%), saturation of the 4-CH3 of δ 2.88 enhanced the signal due to 5-NH at δ 11.16 (12.3%) and saturatoin of the 5-NH at 11.16 enhanced the signal due to 4-CH3 at δ 2.88 (2%); m/z (%) 314 (81, M+), 282 (55), 268 (89), 236 (100), 208 (56), 179 (50), 153 (48), 118 (56), 90 (82) and 77 (72) (Found: M+314.1267. C17H18N2O4 requires 314.1266; Ethyl 6-methoxycarbonyl-3,4-dimethylpyrrolo[3,2-f]indole-2-carboxylate (isomer II) as yellow crystals after crystallization from dichloromethane-petroleum ether (0.0584 g, 10.94%), m.p. 242-245° C.; δH ([2H6]-DMSO) 11.36 (1H, s, 7-NH), 10.92 (1H, s, 1-NH), 7.33 (1H, s, 8-H), 7.24 (1H, s 5-H), 4.36 (2H, q, OCH2CH3), 3.89 (3H, s, OCH3), 2.92 (3H, s, 3-CH3), 2.87 (3H, s, 4-CH3), 1.37 (3H, t, OCH2CH3); m/z (%) 314 (60, M+), 282 (50), 268 (62), 236 (60), 208 (60), 179 (55), 165 (34), 152 (52), 134 (48), 127 (56) and 188 (100) (Found: M+314.1267. C17H18N2O4 requires 314.1266); Further elution gave 2-(3′-acetyl-5′-ethoxycarbonyl-4′-methylpyrrol-2-ylmethyl-5-methoxycarbonylpyrrole as off-white crystals after crystallization from dichloromethane-petroleum ether (0.0912 g, 16.16%), m.p. 160-162° C.; δH (CDCl3), 10.40 (1H, s, 1-NH), 9.78 (1H, s, 1′-NH), 6.79 (1H, dd J 4 and 2.5, 4-H), 6.09 (1H, dd J 4 and 2.5, 3-H), 4.30 (2H, q, OCH2CH3); 4.22 (2H, s, CH2), 3.80 (3H, s, OCH3), 2.58 (3H, s, CH3), 2.50 (3H, s COCH3), 1.33 (3H, t, OCH2CH3; m/z (%) 332 (66, M+), 300 (55), 271 (54), 254 (66), 227 (61), 211 (55), 183 (65), 155 (59), 128 (66), 106 (85), 94 (45), 78 (66), 51 (37), 43 (100); and 2,3-di(3-acetyl-5-ethoxycarbonyl-4-methylpyrrol-2′-ylmethyl-5-methoxycarbonylpyrrole as off-white crystals after crystallization from benzene-petroleum ether (0.1885 g, 41.15%), m.p. 203-206° C. (Found: C, 62.24; H, 6.16; N, 7.66. C28H33N3O8 requires, C, 62.32; H, 6.16; N, 7.79%); δH (CDCl3) 11.08 (1H, s, NH), 9.42 (1H, s, NH), 9.13 (1H, s, NH), 6.63 (1H, d J 2, 4-H), 4.33 (2H, q, OCH2CH3); 4.32 (2H, q, OCH2CH3), 4.13 (2H, s, 2-CH2), 4.11 (2H, s, 3-CH2), 3.77 (3H, s, OCH3), 2.61 (3H, s, CH3), 2.59 (3H, s, CH3), 2.57 (6H, s, 2×CH3), 1.37 (3H, t, OCH2CH3), 1.36 (3H, t, OCH2CH3). under reflux After the clay had been filtered off washed well with 1,2-dichloroethane, evaporation of the combined filtrates under reduced pressure gave an oil Chromatographic separation of an oil eluting with (5-40%) ethylacetate in hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of ethyl 5-acetoxymethyl-4-acetyl-3-methylpyrrole-2-carboxylate (0.267 g, 1.0 mmol) and 3-carbethoxy-2-methylpyrrole (0.153 g, 1.0 mmol) in 1,2-dichloroethane (10 cm3) was heated at reflux and stirred with Montmorillonite clay (1 g) for 18 h. After filtration from clay and washing well with 1,2-dichloroethane, evaporation of the combined filtrates under reduced pressure gave an oil. This oil was submitted to flash chromatography on silica eluting with (0-20%) ethyl acetate in dichloromethane to give the starting 3-carbethoxy-2-methylpyrrole (0.045 g, 29.4%) and diethyl 1,5-dihydro-3,4,6-trimethylpyrrolo[2,3-f]indole-2,7-dicarboxylate as a colourless solid (0.021 g, 6.14%) m.p. 269° C. (decomp); δH ([2H6]-DMSO)11.34 (1H, s, 5-NH), 11.00 (1H, s, 1-NH), 7.80 (1H, s, 8-H), 4.33 (2H, q, 7-OCH2CH3), 4.26 (2H, q, 2-OCH2CH3), 2.85 (6H, s, 3-CH3 and 4-CH3), 2.69 (3H, s, 6-CH3), 1.39 (3H, t, 7-OCH2CH3), and 1.37 (3H, t, 2-OCH2CH3); saturation of the singlet 8-H at δ 7.80 enhanced the signal due to 1-NH at δ 11.00 (2.3%); m/z (%) 342 (75,M+), 296 (100), 268 (6), 223 (7) and 195 (5) (Found: M+ 342.1580. C19H22N2O4 requires M, 342.1579; λ max EtOH/nm (log ε max.dm3 mol−1 cm−1 378 (3.56), 365 sh (353), 329 (3.83), 3.04 (3.99) and 259 (3.74). Further elution gave diethyl 1,7-dihydro-3,4,6-trimethylpyrrolo[3,2-f]indole-2,5-dicarboxylate as a colourless solid (0.048 g, 14%) m.p. 216-216.5° C. (Found: C, 66.82; H, 6.68; N, 8.17. C19H22N2O4 requires C, 66.65; H, 6.48, N, 8.18%); δ ([2H6]-DMSO) 11.30 (1H, s, 7-NH), 10.91 (1H, s, 1N-H), 7.12 (1H, s, 8-11), 4.35 (2H, q, 5-OCH2CH3), 4.28 (2H, q, 2-OCH2CH3), 2.90 (3H, s, 4-CH3), 2.87 (3H, s, 3-CH3, 2.54 (3H, s, 6-CH3), 1.36 (3H, t, 5-OCH2CH3) and 1.34 (3H, t, 2-OCH2CH3); saturation of the 8-H proton at δ 7.12 enhanced the signals due to 7-NH at δ 11.30 (2.4%) and 1-NH at δ 10.91 (1.8%); m/z (%) 342 (64, M+), 296 (100), 250(5), and 194(9); λ max (EtOH)/nm (log ε max/dm3 mol−1 cm−1) 340 (4.10), 327.5 (4.53) and 270 (4.46), and the starting 5-acetoxymethyl-4-acetylpyrrole (0.029 g, 10.9%). at reflux After filtration from clay washing well with 1,2-dichloroethane, evaporation of the combined filtrates under reduced pressure gave an oil