Cesium carbonate → HCID 16063829, compound

Participants

Reaction Conditions

Reaction Steps

(3R,8aR)-octahydropyrrolo[1,2-a]pyrazin-3-ylmethanol (190 mg, 1.22 mmol, Tetrahedron Asymmetry, 1996, 7(7), 1999-2005) was dissolved in 10 mL of toluene, followed by the 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide [WO 2005/002577] (323 mg, 0.607 mmol), 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (ligand) (57 mg, 0.144 mmol), Pd(dba)2 (35 mg, 0.061 mmol) and, at last, cesium carbonate (297 mg, 0.912 mmol). The mixture was stirred at 130° C. After 3.5 h, more ligand (55 mg, 0.139 mmol) and Pd(dba)2 (35 mg, 0.061 mmol) were added and the reaction left overnight. It was let cool down to room temperature, diluted with 10 mL of MeOH, loaded on a 10 g SCX column, washed with MeOH and eluted with 1M methanolic ammonia. The sample coming from the SCX column was further purified by flash chromatography: 1st column: silica, cyclohexane:EtOAc 50:50 to 0:100; 2nd column, NH2-modified silica, cyclohexane:EtOAc 100:0 to 0:100. Isolated 29 mg of the target material.

Provenance & Evidence