Cyanogen Bromide → (R)-4-(6-Bromo-3-fluoro-pyridin-2-yl)-5,5-difluoro-4,6,6-trimethyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine

HRID 1752461ノート

反応式

HRID 1752461 の反応式
[Br:1][C:2]1[N:7]=[C:6]([C@:8]([NH:17][S@@](C(C)(C)C)=O)([CH3:16])[C:9]([F:15])([F:14])[C:10]([OH:13])([CH3:12])[CH3:11])[C:5]([F:24])=[CH:4][CH:3]=1.[N:25]#[C:26]Br>C(O)C>[Br:1][C:2]1[N:7]=[C:6]([C@:8]2([CH3:16])[C:9]([F:14])([F:15])[C:10]([CH3:11])([CH3:12])[O:13][C:26]([NH2:25])=[N:17]2)[C:5]([F:24])=[CH:4][CH:3]=1

参加物

4

反応物 2

HCID 10476Cyanogen BromideHCID 86689145(R)-2-Methyl-propane-2-sulfinic acid [(R)-1-(6-bromo-3-fluoro-pyridin-2-yl)-2,2,difluoro-3-hydroxy-1,3-dimethyl-butyl]-amide

生成物 1

HCID 86689146(R)-4-(6-Bromo-3-fluoro-pyridin-2-yl)-5,5-difluoro-4,6,6-trimethyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine収率 48.9%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

反応条件

温度
85 °C

実験手順

A solution of (R)-2-methyl-propane-2-sulfinic acid [(R)-1-(6-bromo-3-fluoro-pyridin-2-yl)-2,2-difluoro-3-hydroxy-1,3-dimethyl-butyl]-amide (2.95 g, 6.84 mmol) and cyanogen bromide (2.24 g, 20.52 mmol) in dry ethanol (68 ml) was sealed with a glass stopper and heated at 85° C. for 9 hr. The reaction solution was evaporated in vacuo and the crude product was taken up with ethyl acetate and 2M aq. ammonia. The organic phase was washed with water and brine, dried over sodium sulfate, filtered and evaporated. The crude product (2.74 g) was chromatographed over silica gel (toluene/ethyl acetate 6:4) to give the title compound as a colourless solid. 1.19 g (48.9% yield).

後処理

  1. customThe reaction solution was evaporated in vacuo
  2. washThe organic phase was washed with water and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customThe crude product (2.74 g) was chromatographed over silica gel (toluene/ethyl acetate 6:4)

出典と根拠

ORDレコード
ord-0297fbcf22fe41e0a60ce95174414990
出典データセット
uspto-grants-2015_10
特許番号
US09163011B2

反応ノート

読み込み中…