(R)-2-methylpyrrolidine L-tartrate → 4-{3-[2-((2R)-2-Methyl-pyrrolidin-1-yl)-ethyl]-cinnolin-7-yl}-benzonitrile

Participants

Reaction Conditions

Reaction Steps

(2R)-2-methylpyrrolidine (L)-tartrate (0.100 g, 0.425 mmol) was partitioned between toluene (0.5 mL) and 5 M NaOH/brine (1:1, 1 mL total). The organic phase was then added to the product from Example 169D (0.01 g, 0.034 mmol) and heated to 85° C. in a sealed tube for 48 hours. After cooling, the reaction mixture was concentrated under reduced pressure and purified by column chromatography (100% dichloromethane to 95:5 dichloromethane/methanol) to afford the product in 27% yield as a yellow solid. 1H NMR (CD3OD, 300 MHz) δ 8.73 (m, 1H), 8.21 (dd, J=3, 9 Hz, 1H), 8.14 (s, 1H), 8.12 (d, J=9 Hz, 1H), 8.06 (d, J=9 Hz, 2H), 7.92 (d, J=9 Hz, 2H), 3.72-3.48 (m, 4H), 3.15-2.90 (m, 2H), 2.86-2.75 (m, 1H), 2.21-2.10 (m, 1H), 1.98-1.91 (m, 2H), 1.67-1.60 (m, 1H), 1.31 (d, J=6 Hz, 3H). MS (ESI) [M+H]+ at 343.

Provenance & Evidence