Dimethylformamide → HCID 70896246, compound

Participants

Reaction Steps

To a stirred solution of crude lithium (R)-1-(2-(quinuclidin-3-ylamino)ethyl)-1H-indole-7-carboxylate from Step D above in N,N-dimethylformamide (10 mL) was added N,N-diisopropylethylamine (2.3 mL, 13.8 mmol) followed by 1-propanephosphonic acid cyclic anhydride (T3P) (4.1 mL, 13.8 mmol) at room temperature and the mixture was stirred 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) and preparative TLC (60:30:10 methylene chloride/methanol/concentrated ammonium hydroxide) to afford (R)-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). The resulting hydrochloride salt was lyophilized from water to afford (R)-2-(quinuclidin-3-yl)-3,4-dihydro-[1,4]diazepino[6,7,1-hi]indol-1(2H)-one hydrochloride (377 mg, 21%) as a light yellow solid: 1H NMR (500 MHz, DMSO-d6) δ 7.85 (d, J=4.0 Hz, 1H), 7.77 (dd, J=4.3, 1.0 Hz, 1H), 7.45 (d, J=1.5, 1H), 7.14 (t, J=7.5 Hz, 1H), 6.57 (d, J=1.5, 1H), 4.72 (t, J=8.5 Hz, 1H), 4.50 (br s, 1H), 4.34 (br s, 1H), 3.91 (br s, 1H), 3.43-3.18 (m, 4H), 3.00 (t, J=8.0 Hz, 3H), 2.13 (d, J=1.0 Hz, 1H), 1.83-1.71 (m, 3H), 1.63 (t, J=11.0 Hz, 1H); MS (ESI+) m/z 296 (M+H).

Provenance & Evidence