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 1626140ノート

反応式

HRID 1626140 の反応式
[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

参加物

4

反応物 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

生成物 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

試薬・触媒・溶媒 2

HCID 935Nickel触媒HCID 887Methanol溶媒

実験手順

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]+.

後処理

  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

出典と根拠

ORDレコード
ord-751a37249dd1461b8c2f6e4aaf6e0c6a
出典データセット
uspto-grants-2014_07
特許番号
US08785436B2

反応ノート

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