Citric Acid → HCID 57504562, compound

Participants

Reaction Conditions

Reaction Steps

Sodium hydride (60% dispersion in mineral oil) (93 mg, 2.32 mmol) was added to (S)—N-(5-chloropyridin-2-yl)-2-hydroxy-3-((R)-1-(triisopropylsilyloxy)propan-2-yloxy)propanamide (Intermediate AY2) (500 mg, 1.16 mmol) in anhydrous THF (25 mL) at 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 10 minutes and then 3-chloro-2-(4-chloro-1H-pyrazolo[3,4-d]pyrimidin-1-yl)benzonitrile (Intermediate AH6) (370 mg, 1.28 mmol) was added. The reaction mixture was allowed to warm to room temperature and stirred overnight. The reaction mixture was adjusted to pH 7 by addition of 1M citric acid and then diluted with water (20 mL) and EtOAc (50 mL). The organic layer was separated and the aqueous layer re-extracted with EtOAc (2×50 mL). The combined organics were washed with saturated brine (75 mL), dried (MgSO4), filtered and concentrated in vacuo. The crude product was purified by flash silica chromatography, elution gradient 50 to 100% EtOAc in isohexane to afford the product (626 mg, 79%). 1H NMR (400 MHz, CDCl3) δ 0.98-1.09 (21H, m), 1.13-1.17 (3H, m), 3.60-3.77 (3H, m), 4.20-4.33 (2H, m), 5.99-6.03 (1H, m), 7.60-7.70 (2H, m), 7.78-7.81 (1H, m), 7.85-5 7.87 (1H, m), 8.22-8.25 (2H, m), 8.50 (1H, d), 8.60 (1H, d), 8.82 (1H, s); m/z (ES−) (M−H)−=682; HPLC tR=4.04 min.

Provenance & Evidence