反应详情

A mixture of 3-hydroxy-5-[(1S)-2-methoxy-(1-methylethyl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide (0.2 g, 0.66 mmol), 5-(azetidin-1-ylcarbonyl)-2-chloropyridine (158 mg, 0.66 mmol), cesium carbonate (640 mg, 1.97 mmol) and bromotris(triphenylphosphine)copper(I) (62 mg, 0.07 mmol) in DMA (5 mL) was stirred in a ‘Biotage initiator Microwave’ for 3 hours. The mixture was allowed to reach RT and pressure and was partitioned between ethyl acetate (50 mL) and water (50 mL). The ethyl acetate layer was separated, washed with water (5×50 mL), brine (50 mL), dried (MgSO4) and evaporated to a residue which was chromatographed on silica, eluting with a gradient of 0-5% methanol in ethyl acetate, to give the desired compound (113 mg). The compound was partially crystallised from methanol. The material was also partially crystallised from isopropyl alcohol/isohexane or ethyl acetate/isohexane. Mpt (melting onset) 132.7° C.

1. customto reach RT
2. custompressure and was partitioned between ethyl acetate (50 mL) and water (50 mL)
3. customThe ethyl acetate layer was separated
4. washwashed with water (5×50 mL), brine (50 mL)
5. dry with materialdried (MgSO4)
6. customevaporated to a residue which
7. customwas chromatographed on silica
8. washeluting with a gradient of 0-5% methanol in ethyl acetate