2-[4-((R)-2-amino-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-5-fluoro-2-nitro-phenoxy]-1-(5-chloro-pyridin-2-yl)-ethanone → (R)-4-[(RS)-3-(5-chloro-pyridin-2-yl)-7-fluoro-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl]-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine

HRID 1626140노트

반응식

HRID 1626140 반응식
[NH2:1][C:2]1[O:3][CH2:4][C:5]([F:31])([F:30])[C@:6]([C:9]2[C:25]([F:26])=[CH:24][C:12]([O:13][CH2:14][C:15]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][N:18]=3)=O)=[C:11]([N+:27]([O-])=O)[CH:10]=2)([CH3:8])[N:7]=1>[Ni].CO>[Cl:23][C:20]1[CH:21]=[CH:22][C:17]([CH:15]2[NH:27][C:11]3[CH:10]=[C:9]([C@:6]4([CH3:8])[C:5]([F:31])([F:30])[CH2:4][O:3][C:2]([NH2:1])=[N:7]4)[C:25]([F:26])=[CH:24][C:12]=3[O:13][CH2:14]2)=[N:18][CH:19]=1

참가 물질

4

반응물 1

HCID 710089012-[4-((R)-2-amino-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-5-fluoro-2-nitro-phenoxy]-1-(5-chloro-pyridin-2-yl)-ethanone

생성물 1

HCID 71008632(R)-4-[(RS)-3-(5-chloro-pyridin-2-yl)-7-fluoro-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl]-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine

시약·촉매·용매 2

HCID 935Nickel촉매HCID 887Methanol용매

실험 절차

A dispersion of 2-[4-((R)-2-amino-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-5-fluoro-2-nitro-phenoxy]-1-(5-chloro-pyridin-2-yl)-ethanone (160 mg, 349 μmol) and Raney Nickel (30 mg) in methanol (22 ml) was hydrogenated. For the workup, the reaction mixture was filtered through glass fiber paper and the solution was evaporated at reduced pressure. The crude product was purified by flash chromatography on a silica-NH2 phase using a gradient of heptane/ethyl acetate=100:0 to 0 to 100 as the eluent. The (R)-4-[(RS)-3-(5-chloro-pyridin-2-yl)-7-fluoro-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl]-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine was obtained as a red solid. MS (ISP): m/z=413.2 [M+H]+.

후처리

  1. filtrationFor the workup, the reaction mixture was filtered through glass fiber paper
  2. customthe solution was evaporated at reduced pressure
  3. customThe crude product was purified by flash chromatography on a silica-NH2 phase

출처 및 근거

ORD 기록
ord-751a37249dd1461b8c2f6e4aaf6e0c6a
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08785436B2

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