反应详情

温度

23 °C

To a solution of (5R,6R)-5-(5-amino-2-fluoro-phenyl)-6-fluoro-5-methyl-2,5,6,7-tetrahydro-1,4-oxazepin-3-ylamine (intermediate A10B) (20 mg, 78.4 μmol) in 1,2-dichloroethane (200 μl) was added at 23° C. under inert atmosphere 3-chloro-5,6-dihydro-[1]pyrindin-7-one (14.4 mg, 86.2 μmol) and acetic acid (9.41 mg, 8.97 μl, 157 μmol) and the solution was stirred at 23° C. for 30 min. Then sodium triacetoxyborohydride (24.9 mg, 118 μmol) was added and the mixture was stirred at 23° C. for 4 h. After addition of 1 M HCl (1 ml) and stirring for 10 min, the aqueous layer was washed once with dichloromethane, then treated with sat. Na2CO3-sol. to achieve pH 14 and extracted twice with ethyl acetate. The combined organic layers were dried over Na2SO4 and evaporated to give a crude product, which was purified by basic preparative HPLC to give (5R,6R)-5-(5-(3-chloro-6,7-dihydro-5H-cyclopenta[b]pyridin-7-ylamino)-2-fluorophenyl)-6-fluoro-5-methyl-2,5,6,7-tetrahydro-1,4-oxazepin-3-amine (11 mg, 27.0 μmol, 34.5% yield) as a colorless oil. MS (ISP): m/z=407.3.3 [(M+H)+] and 409.3 [(M+2+H)+].

1. stirringthe mixture was stirred at 23° C. for 4 h
2. stirringstirring for 10 min
3. washthe aqueous layer was washed once with dichloromethane
4. additiontreated with sat. Na2CO3-sol
5. extractionextracted twice with ethyl acetate
6. dry with materialThe combined organic layers were dried over Na2SO4
7. customevaporated
8. customto give a crude product, which
9. customwas purified by basic preparative HPLC