Dimethylformamide → HCID 70896171, compound

Participants

Reaction Steps

To a stirred solution of crude lithium (S)-1-(2-(quinuclidin-3-ylamino)ethyl)-1H-indole-7-carboxylate from Step D above in N,N-dimethylformamide (15 mL) was added N,N-diisopropylethylamine (4.3 mL, 26.1 mmol) followed by 1-propanephosphonic acid cyclic anhydride (T3P) (7.8 mL, 26.1 mmol) and the reaction was stirred at room temperature for 17 h. The reaction was quenched with water, extracted with methylene chloride (3×), washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by column chromatography (silica gel, 60:30:10 methylene chloride/methanol/concentrated ammonium hydroxide) to afford (S)-2-(quinuclidin-3-yl)-3,4-dihydro-[1,4]diazepino[6,7,1-hi]indol-1(2H)-one. This material was dissolved in methanol and treated with HCl (1.25 M solution in methanol) and the mixture was concentrated under reduced pressure. The residue was lyophilized from water to afford (S)-2-(quinuclidin-3-yl)-3,4-dihydro-[1,4]diazepino[6,7,1-hi]indol-1(2H)-one hydrochloride (800 mg, 62%) as a white solid: 1H NMR (500 MHz, CD3OD) δ 7.93 (d, J=4.0 Hz, 1H), 7.77 (dd, J=4.5, 1.0 Hz, 1H), 7.26 (d, J=1.8 Hz, 1H), 7.17 (t, J=8.0 Hz, 1H), 6.59 (d, J=1.8 Hz, 1H), 4.71 (br s, 1H), 4.53 (br s, 1H), 4.46 (d, J=5.5 Hz, 1H), 4.08 (br s, 1H), 4.00-3.96 (m, 1H), 3.86-3.69 (m, 3H), 3.46-3.31 (m, 3H), 2.51 (q, J=5.5 Hz, 1H), 2.26 (br s, 1H), 2.19-1.98 (m, 3H); MS (ESI+) m/z 296 (M+H).

Provenance & Evidence