Hydrochloric Acid → HCID 53251830, compound

Participants

Reaction Steps

To tert-butyl 1-(4-(methylcarbamoyl)-3-phenyl-1,5-naphthyridin-2-yl)ethylcarbamate (110 mg, 0.27 mmol) was added 4N HCl in 1,4-dioxane (1 mL, 15 eq). The resulting mixture was stirred at rt for 30 min. The reaction mixture was diluted with ethyl ether (5 mL). The white solid was filtered and washed with ethyl ether and dried under vacuum. Mass Spectrum (ESI) m/e=307 (M+1). To a solution of the amine HCl salt in DMF (3 mL) was added 4-amino-6-chloropyrimidine-5-carbonitrile (41.8 mg, 1.0 eq) and DIEA (0.19 mL, 4.0 eq). The resulting mixture was heated to 105° C. for 2 h. After cool to rt, EtOAc (10 mL) was added and the mixture was washed with water (3×3 mL), brine and dried over sodium sulfate. The solvent was removed and the residue was purified by combiflash (1:20, MeOH/DCM) to afford 2-(1-(6-amino-5-cyanopyrimidin-4-ylamino)ethyl)-N-methyl-3-phenyl-1,5-naphthyridine-4-carboxamide. After chiral HPLC separation (isopropanol/hexane gradient, AD column), (S)-2-(1-(6-amino-5-cyanopyrimidin-4-ylamino)ethyl)-N-methyl-3-phenyl-1,5-naphthyridine-4-carboxamide and (R)-2-(1-(6-amino-5-cyanopyrimidin-4-ylamino)ethyl)-N-methyl-3-phenyl-1,5-naphthyridine-4-carboxamide were obtained as white solid.

Provenance & Evidence