3-Cyanopyridine → (S)-2-((5-cyano-3-fluoro-6-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl)amino)-3,3-dimethylbutyl methanesulfonate

HRID 1055086노트

반응식

HRID 1055086 반응식
C(#N)C1C=CC=NC=1.[F:9][C:10]1[C:11]([NH:38][C@@H:39]([C:42]([CH3:45])([CH3:44])[CH3:43])[CH2:40][OH:41])=[N:12][C:13]([C:18]2[C:26]3[C:21](=[N:22][CH:23]=[C:24]([F:27])[CH:25]=3)[N:20]([S:28]([C:31]3[CH:37]=[CH:36][C:34]([CH3:35])=[CH:33][CH:32]=3)(=[O:30])=[O:29])[CH:19]=2)=[C:14]([CH:17]=1)[C:15]#[N:16].C(N(CC)CC)C.[CH3:53][S:54](Cl)(=[O:56])=[O:55]>ClCCl>[CH3:53][S:54]([O:41][CH2:40][C@@H:39]([NH:38][C:11]1[C:10]([F:9])=[CH:17][C:14]([C:15]#[N:16])=[C:13]([C:18]2[C:26]3[C:21](=[N:22][CH:23]=[C:24]([F:27])[CH:25]=3)[N:20]([S:28]([C:31]3[CH:37]=[CH:36][C:34]([CH3:35])=[CH:33][CH:32]=3)(=[O:29])=[O:30])[CH:19]=2)[N:12]=1)[C:42]([CH3:45])([CH3:44])[CH3:43])(=[O:56])=[O:55]

참가 물질

6

반응물 4

HCID 793-CyanopyridineHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 71247622(S)-5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-6-((1-hydroxy-3,3-dimethylbutan-2-yl)amino)nicotinonitrile

생성물 1

HCID 86714761(S)-2-((5-cyano-3-fluoro-6-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl)amino)-3,3-dimethylbutyl methanesulfonate수율 97.5%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a cold (0° C.) solution of (S)-5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-6-(1-hydroxy-3,3-dimethylbutan-2-yl)amino)nicotinonitrile, 98a, (3.77 g, 7.17 mmol) and triethylamine (1.25 mL, 8.96 mmol) in dichloromethane (75 mL) was added methanesulfonyl chloride (0.69 mL, 8.96 mmol). The solution was stirred at room temperature for 1 hour. The solvent was removed under reduced pressure and water (100 mL) and EtOAc (200 mL) were added. The organic phase was separated, dried (MgSO4), filtered and concentrated under reduced pressure to afford 4.22 g of the desired product as a yellow foamy solid that was used without further purification: LC/MS (60-90% ACN/water 5 min with 0.9% FA, C4) m/z 604.45 (M+H) retention time=2.03 minutes.

후처리

  1. customThe solvent was removed under reduced pressure and water (100 mL) and EtOAc (200 mL)
  2. additionwere added
  3. customThe organic phase was separated
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-cca0fd1149164766bde34951dc1aac76
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09394302B2

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