2-Methyl-2-butene → 6-chloro-5-[2-(morpholin-4-yl)pyrimidin-5-yl]-1H-indole-3-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

6-chloro-5-[2-(morpholin-4-yl)pyrimidin-5-yl]-1H-indole-3-carbaldehyde (159 mg, 0.464 mmol) was dissolved in acetonitrile (6 mL) and warm tert-butanol (6 mL) and treated with 2-methyl-2-butene. The reaction mixture was cooled to 0° C. and treated with a solution of sodium chlorite (630 mg, 9.27 mmol) and sodium phosphate monobasic dihydrate (1.45 g, 9.30 mmol) in water (5 mL) via addition funnel. The mixture was stirred at room temperature overnight. The reaction mixture was then concentrated in vacuo to remove the organics and extracted with EtOAc (3×20 mL). The combined organics were washed with brine (20 mL), dried and concentrated in vacuo to give a crude, which was purified by prep-HPLC to give 6-chloro-5-[2-(morpholin-4-yl)pyrimidin-5-yl]-1H-indole-3-carboxylic acid (67.6 mg, 40.60% yield) as a white solid. MS (ES+) 359.1 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 12.22 (s, 1 H), 12.03 (s, 1 H), 8.49 (m, 2 H), 8.12 (m, 1 H), 7.97 (s, 1 H), 7.69 (s, 1 H), 3.78 (m, 4 H), 3.70 (m, 4 H).

Provenance & Evidence