Dimethyl Sulfoxide → HCID 178496660, compound

Participants

Reaction Steps

A vessel was charged with (R)-3-(difluoromethyl)-5-(2-(3,5-dimethyl-1-tosyl-1H-indazol-4-yl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-1-methyl-1H-pyrazole-4-carbaldehyde (54 mg, 0.074 mmol), hydroxylamine hydrochloride (77 mg, 1.105 mmol), and DMSO (491 μL). The vessel was capped and placed in a sand bath preheated to 100° C. and the reaction mixture was stirred at that temperature. After 2 h the mixture was diluted with methanol and transferred to a round-bottomed flask. Potassium carbonate was added, and the mixture stirred for 2 h at 60° C., then allowed to cool to room temperature. The mixture was then filtered through Celite and concentrated, redissolved in methanol, filtered through a syringe filter, and purified by HPLC (15-100% CH3CN in water with 0.1% NH4OH) to provide (R)-3-(difluoromethyl)-5-(2-(3,5-dimethyl-1H-indazol-4-yl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-1-methyl-1H-pyrazole-4-carbonitrile. 1H NMR (400 MHz, CD3OD) δ ppm 7.44 (d, J=8.6 Hz, 1 H), 7.31 (d, J=8.6 Hz, 1 H), 6.54-6.92 (m, 1 H), 4.64 (d, J=14.8 Hz, 1 H), 4.53 (d, J=14.8 Hz, 1 H), 3.85-3.95 (m, 1 H), 3.80 (s, 3 H), 3.67-3.75 (m, 2 H), 3.52 (dd, J=13.4, 1.3 Hz, 1 H), 3.37 (s, 3 H), 3.01-3.10 (m, 4 H), 2.26 (s, 3 H), 2.01 (s, 3 H), 1.97-2.06 (m, 1 H), 1.67-1.79 (m, 1 H), 1.01 (s, 3 H), 0.93 (s, 3 H); MS (ESI+) m/z 576.4 (M+H)+.

Provenance & Evidence