Ammonia → HCID 57520619, compound

Participants

Reaction Steps

In a pressure tube (R)-5-[5-((RS)-3-chloro-6,7-dihydro-5H-[1]pyrindin-7-ylamino)-2-fluoro-phenyl]-5-methyl-morpholin-3-thione (58 mg, 0.15 mmol) was dissolved in a solution of ammonia in methanol (7M, 0.5 ml). Then tert-butyl hydroperoxide (70% in water) (0.07 ml, 0.74 mmol) was added. The tube was sealed and the mixture stirred for 4 hours at room temperature. For the workup, the solution was evaporated at reduced pressure. NMR analysis showed still starting material. The residue was redissolved in a solution ammonia in methanol (7M, 0.5 ml) and heated to 50° C. for 3 days. Thereafter, another 0.5 ml were added, then after 1 day another 0.071 ml (0.74 mmol) of tert-butyl hydroperoxide. After stirring at room temperature for 4.5 hours the reaction mixture was quenched with a saturated aqueous solution of sodium carbonate, thereafter extracted with ethyl acetate. The combined organic layers were dried over sodium sulphate, then evaporated at reduced pressure. The crude material was purified by flash chromatography on silica gel using a gradient of heptane/ethyl acetate=100:0 to 0:100 as the eluent. The [3-((R)-5-amino-3-methyl-3,6-dihydro-2H-[1,4]oxazin-3-yl)-4-fluoro-phenyl]-((RS)-3-chloro-6,7-dihydro-5H-[1]pyrindin-7-yl)-amine was obtained as a white foam (33 mg, 60%); (calculated) C19H20ClFN4O [374.85]; (found) [M+H]+=375.

Provenance & Evidence