Tetrabutylammonium Fluoride → HCID 57504405, compound

Participants

Reaction Steps

1M tetrabutylammonium fluoride in THF (0.503 mL, 0.50 mmol) was added to (2S)-2-(1-(2-chloro-6-cyanophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-methylpyridin-2-yl)-3-((R)-1-(triisopropylsilyloxy)propan-2-yloxy)propanamide (Intermediate AH8) (334 mg, 0.50 mmol) in THF (10 mL) under nitrogen. The resulting mixture was stirred at ambient temperature for 1 hour. The reaction mixture was quenched with saturated NH4Cl (2 mL), diluted with DCM (25 mL) and poured onto a phase separator. The organic phase was reduced and the residue was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 50 mm diameter, 150 mm length), using decreasingly polar mixtures of water (containing 0.1% formic acid) and MeCN as eluents to afford the product (129 mg, 50.5%). 1H NMR (400 MHz, CDCl3) d 1.21-1.14 (3H, m), 2.30 (3H, s), 3.62 (2H, m), 3.78 (1H, m), 4.14-4.03 (1H, m), 4.28 (1H, dd), 6.10-6.03 (1H, m), 7.54 (1H, dd), 7.62 (1H, t), 7.79 (1H, m), 7.86 (1H, m), 8.07 (2H, d), 8.51 (1H, d), 8.62 (1H, d), 9.28-9.18 (1H, m), OH not observed. m/z (ES+) (M+H)+=508; HPLC tR=1.92 min. ee 90%

Provenance & Evidence