反应详情

温度

100 °C

3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (0.249 g, 1.22 mmol), 8-chloro-2-cyclopropyl-4-methyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (0.292 g, 1.22 mmol), Palladium acetate (0.027 g, 0.12 mmol), 2-(Dicyclohexylphosphino)biphenyl (0.043 g, 0.12 mmol) and Cesium carbonate (0.399 g, 1.22 mmol) were added in a microwave vial. The mixture was capped and flushed with argon. 1,2-dimethoxyethane (4 mL) was added and the mixture was run in a microwave for 60 minutes at 100°C. No product, only unreacted startingmaterial. Added 1 eq CsCO3, and 0.1 eq ligand and palladium acetate, flushed with argon and run in the microwave at 100°C for 60 min. 9% product according to LCMS. Added 0.1 eq ligand and palladium acetate, flushed with argon and run in the microwave at 100°C for 60 min. No change. Added 0.1 eq ligand and palladium acetate, flushed with argon and run in the microwave at 100°C for 60 min. No change. Decided to isolate the intermediate and eventual product. The reaction mixture was filtrated through celite and concentrated. The crude was purified by preparative chromatography. The little product- containing fractions were collected but HPLC showed that they were not pure. The solvent was evaporated and the crude was partitioned between dichloromethane and sat. NaHCO3 (aq). The organic layer was separated with a phase separator and concentrated. Have 3 mg which is not pure. Discarded. Fractions with the intermediate 8-chloro-2-cyclopropyl-4-methyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine was collected, concentrated and the residue was partitioned with dichloromethane and sat. NaHCO3 (aq). The organic layer was separated, dried (Na2SO4) and concentrated giving 0.036 g of 8-chloro-2-cyclopropyl-4-methyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine.