Ammonium Chloride → N-(5-cyano-4-((2-(trifluoromethoxy)ethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-6-((N-methylacetamido)methyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

Participants

Reaction Conditions

Reaction Steps

To a solution of phenyl 7-(dimethoxymethyl)-6-((N-methylacetamido)methyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate (intermediate 54A, 145 mg, 0.349 mmol) and 6-amino-4-((2-(trifluoromethoxy)ethyl)amino)nicotinonitrile (intermediate 102E, 103 mg, 0.419 mmol) in THF (6 ml) was slowly added 1M LHMDS in THF (0.699 ml, 0.699 mmol) at −78° C. The reaction mixture was stirred at −78° C. for 30 min, then left to warm to room temperature overnight. The reaction mixture was poured into saturated NH4Cl solution. The aqueous was extracted with DCM (×2). The combined organic extracts were concentrated under reduced pressure. Purification of the crude product by chromatography on silica eluting with 0-100% EtOAc in heptane, then eluting with 0-100% (DCM:MeOH+0.1% NH3 9:1) in DCM afforded the title compound. (UPLC-MS 3) Rt=1.07 min; MS m/z [M+H]+ 566.

Provenance & Evidence