3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline → (S)-N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine

Participants

Reaction Conditions

Reaction Steps

3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (0.213 g, 0.89 mmol), Palladium(II) acetate (0.017 g, 0.07 mmol), 2-(Dicyclohexylphosphino)biphenyl (0.026 g, 0.07 mmol) and Cesium carbonate (0.722 g, 2.22 mmol) were put in a 20 mL microwave vial and sealed. The vial was flushed with argon. (S)-8-chloro-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (0.203 g, 0.74 mmol) in DME (5 mL) was added and additional 5 mL was added to the vial. The reaction mixture was run in the microwave at 100°C for 80 minutes. Reaction still not complete. Additional palladium(II)acetate (0.1 eq) and 2-(dicyclohexylphosphino)biphenyl (0.1 eq) were added and the reaction was run again in the microwave for 60 minutes. Have about 14% oxazepine left. Heated for additional 45 minutes. 10% oxazepine left. Added 0.1 eq palladium(II)acetate, 0.1 eq 2-(dicyclohexylphosphino)biphenyl and 0.3 eq of 3-methoxy-4-(4-methyl-1Himidazol-1-yl)aniline and let the reaction run in the microwave for additional 60 minutes. The reaction mixture was filtrated through celite, concentrated and purified first by silica flash chromatography using methanol in dichlorometane (0 to 4%). The productcontaining fractions were pooled and purified further by preparative chromatography. The productcontaining fractions were pooled, concentrated and partitioned between sat. NaHCO3 (aq) and dichloromethane. The organic layer was washed with brine, dried (MgSO4) and concentrated giving 0.091 g of the product.

Provenance & Evidence