Реакция #685
ord-2d0a333d9cfc43c6a6709471b22f0443
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2016-05-18 **time temp comment** 1 14:20 21 (S)-2-(2-chloro-5-methylpyrimidin-4-yl)-7-(3,4-difluorobenzyl)-6-(methoxymethyl)-6,7-dihydroimidazo[1,2-a]pyrazin-8(5H)-one (2.2 g, 5.07 mmol), 1-methyl-1H-pyrazol-5-amine (0.754 g, 7.61 mmol) and cesium carbonate (3.30 g, 10.14 mmol) was charged to a 100mL reactor. 2-methyl tetrahydrofuran (1.2 L) and water (0.120 L) was charged. Degassed (6x vac/N2) 14:25 21 2'-(dicyclohexylphosphanyl)-N,N-dimethyl-[1,1'-biphenyl]-2-amine (dave phos) (0.160 g, 0.41 mmol) and Pd2dba3 (0.186 g, 0.20 mmol) was added. degassed (6x vac/N2). 14:25 21 heated to 80 magnetic stirrer under nitrogen. IPC1 (1,5h) SFC-MS indicates 9.5% conversion. 2016-05-19 08:00 reflux IPC2 (18h) SFC-MS indicates 66% conversion. 14.00 reflux IPC3 (23h) SFC-MS indicates 72% conversion. The reaction mixture was cooled to 40°C and 1 eq. of catalyst and ligand was added, 0.17g Pd and 0.15g Davefos. degassed 6 times. Jacket to 80°C , stirred over night. 2016-05-20 07:45 reflux IPC4 42h complete conversion. 1.19 g of silicycle was added and the temperature was set to ambient. . 10:18:07 rt the mixture was filtered through a celite filter (25µ). the filter cake was washed with EtOAc (2x 10 ml). 10:30:44 rt the filtrate was transfered to a sep funnel and washed with aq citric acid (0,5M, 15 ml) and water (5 ml). Unfortunately when washing with water some diluted HCl was used, so the reaction mixture was basified with bicarbonate solution prior to the final water wash. The organic layer was evaporated to a solid, 2.7g Material sent to SSL for separation 2016-05-23. Yield after chromatography: 1.38g