3-(Chloromethyl)-2-methoxypyridine → HCID 57941441, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of (4R,7S)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 42; 476 mg, 1.56 mmol), 3-chloromethyl-2-methoxy-pyridine (Intermediate 51; 989 mg, 6.3 mmol) and tetrabutylammonium iodide (580 mg, 1.6 mmol) in dimethylformamide (16 mL) was heated at 100° C. for 48 h. The solvent was evaporated and dichloromethane (250 mL) was added. The solution was washed with concentrated aqueous sodium thiosulfate (2×100 mL), saturated aqueous sodium hydrogen carbonate (100 mL), water (6×500 mL) and brine (100 mL), dried (magnesium sulfate), filtered, evaporated and purified using a Biotage 40L system, eluting with 1-2% methanol/dichcloromethane to give an oily material. This material was dried on a vacuum pump, co-evaporated three times with ethanol, and finally held again under high vacuum to give (4R,7S)-2-(2,4-difluoro-phenyl)-1-(2-methoxy-pyridin-3-ylmethyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (201 mg, 30%) as an off-white solid. ES(+)-MS (M+H) 426.

Provenance & Evidence