Cesium carbonate → HCID 16063829, compound

Participants

Reaction Conditions

Reaction Steps

The title compound was prepared starting from 323 mg (0.608 mmoles) of 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide (WO 2005/002577), 1.216 mg (0.160 mmol) of (3R,9aR)-octahydro-2H-pyrido[1,2-a]pyrazin-3-ylmethanol (Tetrahedron Asymmetry, 1996, 7(7), 1999-2005), 35 mg of bis(dibenzylideneacetone)palladium (0.061 mmol), 57 mg of 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (0.145 mmol), 297 mg (0.912 mmol) of cesium carbonate; the reagents were dissolved in 10 ml of toluene and stirred at 140° C. in a closed vial for 4 hours. More dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (57 mg 0.145 mmol), and bis(dibenzylideneacetone)palladium (35 mg, 0.061 mmol) were added and the reaction kept at 140° C. for additional 4 hours. The crude material was loaded on a SCX cartridge, the neutral fractions were washed with methanol and the basic eluted with 2M ammonia in methanol and collected. The solvent was removed and the residue purified by chromatography (Silica) eluting with ethyl acetate, followed by a gradient from methylene chloride to methylene chloride:methanol 95:5. The cleanest fractions were purified further by chromatography on an NH2 silica cartridge with a gradient cyclohexane to cyclohexane:ethyl acetate 70:30, affording 29 mg of the title compound as pale yellow solid.

Provenance & Evidence