Dimethylformamide → HCID 66772518, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of the crude lithium (S)-1-benzyl-3-(2-(quinuclidin-3-ylamino)ethyl)-1H-indazole-4-carboxylate (509 mg, 1.24 mmol) from Step D above in DMF (25 mL) was added N,N-diisopropylethylamine (1.22 mL, 7.44 mmol) at 0° C. To the above reaction was added 1-propanephosphonic acid cyclic anhydride (T3P) (50% in ethyl acetate, 3.94 g, 6.2 mmol) and the mixture was stirred at 0° C. for 1.5 h. The reaction mixture was treated with brine (25 mL) and saturated aqueous solution of sodium bicarbonate (25 mL). The compound was extracted with dichloromethane (4×100 mL) and the combined organic layers were washed with brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude material was purified by column chromatography (silica gel, 90:9:1 dichloromethane/methanol/concentrated ammonium hydroxide) to afford (S)-2-benzyl-7-(quinuclidin-3-yl)-8,9-dihydro-2H-azepino[5,4,3-cd]indazol-6(7H)-one (316 mg, 66%) as a white solid: 1H NMR (300 MHz, CDCl3) δ 7.98-7.95 (m, 1H), 7.45-7.43 (m, 2H), 7.32-7.25 (m, 3H), 7.119-7.15 (m, 2H), 5.57 (s, 2H), 4.85-4.68 (1H), 4.20-3.90 (m, 2H), 3.45-3.38 (m, 1H), 3.35-2.90 (m, 7H), 2.25-2.15 (m, 1H), 1.95-1.55 (m, 4H); MS (ESI+) m/z 387 (M+H).

Provenance & Evidence