Citric Acid → HCID 57504386, compound

Participants

Reaction Conditions

Reaction Steps

Sodium hydride (10.78 mg, 0.27 mmol) was added to (S)-2-hydroxy-3-isopropoxy-N-(5-methylpyridin-2-yl)propanamide (Intermediate C7) (53.5 mg, 0.22 mmol) in anhydrous THF (50 mL) at 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 10 minutes and then 4-phenoxy-1-(2-(trifluoromethyl)phenyl)-1H-pyrazolo[3,4-d]pyrimidine (Intermediate Z1) (80 mg, 0.22 mmol) was added. The reaction mixture was allowed to warm to room temperature and stirred for 1 hour. The reaction mixture was neutralised with 1M citric acid and the majority of the THF removed in vacuo. The reaction mixture was diluted with water (20 mL) and ethyl acetate (50 mL). The organic layer was separated and the aqueous layer re-extracted with ethyl acetate (2×100 mL). The combined organics were washed with saturated brine (75 mL), dried (MgSO4) and evaporated. The crude product was purified by flash silica chromatography, eluting with 50 to 100% ethyl acetate in isohexane. The residue was purified by preparative HPLC using decreasingly polar mixtures of water (containing 1% ammonia) and MeCN as eluents to afford the product (60.0 mg, 53.4%). 1H NMR (400 MHz, CDCl3) δ 1.17-1.20 (6H, m), 2.30 (3H, s), 3.69-3.75 (1H, m), 4.09 (2H, d), 6.01 (1H, t), 7.52-7.56 (2H, m), 7.69 (1H, t), 7.76 (1H, t), 7.91 (1H, d), 8.10-8.15 (2H, m), 8.42 (1H, s), 8.56 (1H, s), 8.72 (1H, s); m/z (ES+) (M+H)+=501; HPLC tR=2.70 min.

Provenance & Evidence