Dimethylformamide → HCID 178515171, compound

Participants

Reaction Steps

To a solution of crude lithium (R)-3-((quinuclidin-3-ylamino)methyl)-1H-indazole-4-carboxylate from Step B above in N,N-dimethylformamide (30 mL) was added N,N-diisopropylethylamine (5.7 mL, 34.4 mmol) followed by 1-propanephosphonic acid cyclic anhydride (T3P) (17 mL, 28.65 mmol) at 0° C. for 17 h. The solution was concentrated and purified by column chromatography (silica gel, 70:30:3 dichloromethane/methanol/concentrated ammonium hydroxide), SCX-2 column and preparative TLC (silica gel, 70:30:3 dichloromethane/methanol/concentrated ammonium hydroxide) to afford (R)-7-(quinuclidin-3-yl)-7,8-dihydropyrazolo[3,4,5-de]isoquinolin-6(2H)-one. This material was dissolved in methanol and treated with HCl (1.25 M solution in methanol). The mixture was concentrated under reduced pressure. The residue was lyophilized from water to afford (R)-7-(quinuclidin-3-yl)-7,8-dihydropyrazolo[3,4,5-de]isoquinolin-6(2H)-one (373 mg, 23%) as a light-yellow solid. 1H NMR (500 MHz, D2O) δ 7.32 (d, J=8.3 Hz, 1H), 7.26 (dd, J=8.3, 6.9 Hz, 1H), 7.10 (d, J=6.9 Hz, 1H), 4.83 (d, J=17.1 Hz, 1H), 4.71 (d, J=16.8 Hz, 1H), 4.53 (t, J=8.9 Hz, 1H), 3.60 (dd, J=12.9, 10.6 Hz, 1H), 3.33-3.13 (m, 5H), 2.32 (br s, 1H), 2.13-2.07 (m, 1H), 2.03-1.85 (m, 3H). MS (ESI+) m/z 283 (M+H); HPLC>99% (AUC), tR 10.94 min.

Provenance & Evidence