Reaction Steps
To a mixture of 5.4 mL of fuming nitric acid and 0.6 mL of concentrated sulfuric acid, chilled at 0° C., was added 600 mg (2.61 mmol) of 20. The reaction mixture was stirred at 0° C. for 5 min and then poured into a mixture of 20 g of cracked ice and 30 mL of chloroform. The mixture was neutralized with saturated aqueous sodium bicarbonate and vigorously stirred to extract the product into the chloroform layer. The chloroform layer was removed and the aqueous layer extracted with 3×30 mL portions of chloroform. Drying the combined chloroform extracts (sodium sulfate) and concentration afforded 22a as a yellow solid. Recrystallization was carried out from chloroform/hexane: 500 mg (69%) yield; m.p. 198° C.; TLC (chloroform/methanol [85:15]), Rf =0.44; IR (KBr pellet) 1689, 1525, 1517, 1492, 1459, 1421, 1369, 358, 1263, 1249 cm-1 ; 1H NMR (CDCl3) δ7.89 (1H, s, amide proton), 7.38 (1H, s, C(8) proton), 4.14 (2H, t, J=7.4 HZ, C(1) methylene), 3.14 (2H, t, J=7.4 Hz, C(3) methylene), 2.78 (2H, quintet, J=7.4 Hz, C(2) methylene), 2.41 (3H, s, 7-methyl), 2.21 (3H, s, acetamido methyl); mass spectrum (EI mode) m/z 274 (P+), 256 (P+ -H2O), 232 (P+ -ketene), 228 (P+ -NO2). Anal. Calcd for C13H14N4O3.1.5 H2O: C, 51.84; H, 4.68; N, 18.59. Found: C, 51.64; H, 4.68; N, 18.52. Acetamido-7-methyl-5-nitro-2,3-dihydro-1H-pyrrolo[2-a]benzimidazole-3-Acetate (22b). To a mixture of 2 mL of fuming nitric acid and 0.8 mL of concentrated sulfuric acid, chilled in a dry-ice acetone bath, was added 400 mg (1.39 mmol) of 21 portionwise over a two min period. The reaction mixture was removed from the ice bath and stirred for 15 min while coming to room temperature and then poured into a mixture of 50 g ice and 50 mL of chloroform. Saturated sodium bicarbonate was added to the above mixture with vigorous stirring until the pH was neutral. The chloroform layer was separated and the aqueous layer extracted 2× with 50 mL portions of chloroform. Drying the combined extracts (sodium sulfate), concentration to a residue, and trituration with ethyl acetate afforded crystalline 22b: 310 mg (67%) yield. Recrystallization was carried out from chloroform/hexane: mp 204° C.; TLC (chloroform/methanol [9;1]), Rf =0.24; IR (KBr pellet) 1750, 1681, 1528, 1370, 1360, 1270, 1083 cm-1 ; 1H NMR (CDCl3) δ7.89 (1H, s, amide proton), 7.47 (1H, s, C(8) proton), 6.17 (1H, dd, J=7.5 Hz, J=3.5 Hz, C(3) proton), 4.2 (2 H, m, C(1) diastereomeric methylene), 3.17 and 2.72 (2H, 2×m, C(2) diastereomeric methylene), 2.43 (3H, s, 7-methyl) 2.22 and 2.13 (6H, 2×s, acetate and acetamido protons); mass spectrum (EI mode) m/z 332 (P+), 314 (P+ -H2O), 286 (P+ -NO2). Anal. Calcd for C15H16N4O5.0.25 H2O: C, 53.49; H, 4.93; N, 16.62. Found: C, 53.78; H, 4.62; N, 16.42.
