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 1055086ノート

反応式

HRID 1055086 の反応式
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]

参加物

6

反応物 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

生成物 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 methanesulfonate収率 97.5%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-cca0fd1149164766bde34951dc1aac76
出典データセット
uspto-grants-2016_07
特許番号
US09394302B2

反応ノート

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