Citric Acid → HCID 57504494, compound

Participants

Reaction Conditions

Reaction Steps

A solution of trimethylaluminium (2M in hexane) (0.491 mL, 0.98 mmol) was added dropwise to a stirred solution of 5-methylpyridin-2-amine (92 mg, 0.85 mmol) in toluene (5 mL) cooled to 0° C., over a period of 1 minute under nitrogen. The resulting solution was stirred at 0° C. for 20 minutes. A solution of (2S)-methyl 5-(tert-butyldimethylsilyloxy)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)pentanoate (Intermediate O2) (420 mg, 0.85 mmol) in toluene (5 mL) was added dropwise over a period of 2 minutes. The resulting solution was stirred at 0° C. for 10 minutes allowed to warm to ambient temperature and then heated at 60° C. for 20 hours. The mixture was cooled and 1M citric acid (10 mL) added with vigorous stirring. The mixture was diluted with ethyl acetate (35 mL), washed with water (10 mL) and brine (10 mL), dried (MgSO4) and evaporated. The crude product was purified by flash silica chromatography, eluting with 50 to 100% ethyl acetate in isohexane to give the product (180 mg, 37%). 1H NMR (400 MHz, CDCl3) δ 0.04 (3H, s), 0.05 (3H, s), 0.89 (9H, s), 1.78-1.81 (2H, m), 2.20-2.30 (2H, m), 2.29 (3H, s), 3.71 (2H, t), 5.90-5.93 (1H, m), 7.45 (1H, dd), 7.51 (1H, dd), 7.99 (1H, dd), 8.07-8.08 (1H, m), 8.14 (1H, d), 8.42 (1H, s), 8.53 (1H, s), 8.60 (1H, dd), 8.62 (1H, s); m/z (ESI+) (M+H)+=568; HPLC tR=3.33 min.

Provenance & Evidence