Sodium hydride → (2S)-2-(1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-((S)-1-methoxypropan-2-yloxy)-N-(5-methylpyrazin-2-yl)propanamide

Participants

Reaction Steps

Sodium hydride (23.17 mg, 0.58 mmol) was added in one portion to a stirred solution of (S)-2-hydroxy-3-((S)-1-methoxypropan-2-yloxy)-N-(5-methylpyrazin-2-yl)propanamide (Intermediate Y3) (78 mg, 0.29 mmol) in anhydrous THF (5 mL) at 0° C. The resulting mixture was stirred for 10 minutes and then a solution of 4-chloro-1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidine (Intermediate B1) (115 mg, 0.43 mmol) in dry THF (2 mL) added dropwise over 1 minute and the reaction was allowed to warm up to ambient temperature and stirred for 1 hour. The reaction mixture was diluted with ethyl acetate (20 mL), and washed sequentially with water (10 mL) and saturated brine (5 mL). The organic layer was dried (MgSO4) and evaporated. The crude product was purified by flash silica chromatography, eluting with 0-100% ethyl acetate in isohexane to afford the product (115 mg, 80%). 1H NMR (400 MHz, CDCl3) δ 1.20 (d, 3H), 2.53 (s, 3H), 3.35-3.50 (m, 5H), 3.79-3.88 (m, 1H), 4.08-4.16 (m, 1H), 4.21-4.28 (m, 1H), 5.94-5.99 (m, 1H), 7.43-7.55 (m, 3H), 7.60-7.63 (m, 1H), 8.12-8.13 (m, 1H), 8.40 (s, 1H), 8.58 (s, 1H), 9.18 (s, 1H), 9.42 (d, 1H). m/z (ESI+) (M+H)+=498.36; HPLC tR=2.25 min.

Provenance & Evidence