تفاعل #657338
ord-36df0272358943c2854b524581ebdd81
معادلة التفاعل
المتفاعلات
المذيبات
ظروف التفاعل
المعالجة
- 1أخرىThe reaction mixture was sparged with argon
- 2أخرىthe reaction vessel sealed
- 3أخرى(screw cap)
- 4أخرىplaced in 100° C.
- 5أخرىpartitioned between ethyl acetate and water (100 mL each)
- 6أخرىThe organic layer was separated
- 7غسيلwashed with saturated brine solution (100 mL)
- 8تجفيفthen dried (MgSO4)
- 9ترشيحfiltered
- 10تركيزconcentrated
- 11أخرىThe product was purified
- 12غسيلthen eluted with 2 M ammonia in methanol in dichloromethane (0-8% 2 M ammonia in methanol linear gradient over 18 column volumes at a flow rate of 60 mL/min)
الإجراء التجريبي
To a solution of {3-chloro-6-[2-(3-fluoro-phenyl)-ethyl]-benzo[1,4]oxazin-2-ylidenemethyl}-dimethyl-amine (500 mg, 1.45 mmol, 1 equiv) and [3-(4-ureido-piperidin-1-yl)-propyl]-carbamic acid tert-butyl ester (435 mg, 1.45 mmol, 1 equiv) in dioxane (15 mL) was added palladium(II) acetate (3.2 mg, 0.0145 mmol, 0.01 equiv), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (xantphos, 17 mg, 0.029 mmol, 0.02 equiv) and cesium carbonate (709 mg, 2.18 mmol, 1.5 equiv). The reaction mixture was sparged with argon then the reaction vessel sealed (screw cap) and placed in 100° C. oil bath. After 14 h at 100° C. the reaction was cooled to 23° C., and then partitioned between ethyl acetate and water (100 mL each). The organic layer was separated and washed with saturated brine solution (100 mL) then dried (MgSO4), filtered and concentrated. The product was purified using an Isco CombiFlash automated chromatography system. The residue was loaded onto an 80 g silica gel column as a solution in dichloromethane (5 mL) then eluted with 2 M ammonia in methanol in dichloromethane (0-8% 2 M ammonia in methanol linear gradient over 18 column volumes at a flow rate of 60 mL/min) to give 313 mg (0.515 mmol, 36%) of the title compound as a yellow/brown solid.