2-Butyn-1-ol → 1-(6-(2-butynyloxy)-5-fluoropyrimidin-4-yl)-trans-2,6-dimethyl-hexahydro-1H-azepine

0.10 g of sodium hydride (60% oil suspention) was suspended in 3 ml of tetrahydrofuran. 0.5 ml of tetrahydrofuran solution of 0.15 g of 2-butyn-1-ol was added dropwise at room temperature therein, and the mixture was stirred for 10 minutes. Into the mixture was added dropwise 0.5 ml of tetrahydrofuran solution of 0.31 g of 1-(6-chloro-5-fluoropyrimidin-4-yl)-trans-2,6-dimethyl-hexahydro-1H-azepine at room temperature, and stirred for 6 hours at 60° C. After the reaction mixture was cooled to near room temperature, the reaction mixture was poured into a saturated ammonium chloride aqueous solution, and the mixture was extracted with tert-butyl methyl ether three times. The organic layers were washed with a saturated sodium chloride aqueous solution, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography to obtain 0.34 g of 1-(6-(2-butynyloxy)-5-fluoropyrimidin-4-yl)-trans-2,6-dimethyl-hexahydro-1H-azepine (hereinafter, referred to as Compound (42)).

1. stirringstirred for 6 hours at 60° C
2. extractionthe mixture was extracted with tert-butyl methyl ether three times
3. washThe organic layers were washed with a saturated sodium chloride aqueous solution
4. dry with materialdried over anhydrous magnesium sulfate
5. concentrationconcentrated

ORD 기록

ord-deade5c307a24fa4be4e2995be47cf14

출처 데이터셋

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08129526B2