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 1752461노트

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HRID 1752461 반응식
[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

참가 물질

4

반응물 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

생성물 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-ylamine수율 48.9%

시약·촉매·용매 1

HCID 702Ethanol용매

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온도
85 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-0297fbcf22fe41e0a60ce95174414990
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09163011B2

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