1H-imidazole-2-carbaldehyde → 2-[5-chloro-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridin-3-yl]-5-fluoro-N-[(3S)-1-(1H-imidazol-2-ylmethyl)-3-piperidyl]pyrimidin-4-amine

HRID 74868

反応式

HRID 74868 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][C@H:18]4[CH2:23][CH2:22][CH2:21][NH:20][CH2:19]4)[C:14]([F:24])=[CH:13][N:12]=3)=[CH:9][N:8]([S:25]([C:28]3[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=3)(=[O:27])=[O:26])[C:5]2=[N:6][CH:7]=1.[NH:35]1[CH:39]=[CH:38][N:37]=[C:36]1[CH:40]=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.C(O)(=O)C.C([O-])(O)=O.[Na+]>[NH:35]1[CH:39]=[CH:38][N:37]=[C:36]1[CH2:40][N:20]1[CH2:21][CH2:22][CH2:23][C@H:18]([NH:17][C:15]2[C:14]([F:24])=[CH:13][N:12]=[C:11]([C:10]3[C:4]4[C:5](=[N:6][CH:7]=[C:2]([Cl:1])[CH:3]=4)[N:8]([S:25]([C:28]4[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=4)(=[O:27])=[O:26])[CH:9]=3)[N:16]=2)[CH2:19]1

参加物

7

反応物 3

HCID 249551H-imidazole-2-carbaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 672851192-[5-chloro-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridin-3-yl]-5-fluoro-N-[(3S)-3-piperidyl]pyrimidin-4-amine2 回

生成物 1

HCID 672877632-[5-chloro-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridin-3-yl]-5-fluoro-N-[(3S)-1-(1H-imidazol-2-ylmethyl)-3-piperidyl]pyrimidin-4-amine

試薬・触媒・溶媒 3

HCID 176Acetic Acid触媒HCID 111,2-Dichloroethane溶媒HCID 516892Sodium Bicarbonate溶媒

反応条件

温度
60 °C

実験手順

To a solution of 2-[5-chloro-1-(p-tolylsulfonyl)pyrrolo[5,4-b]pyridin-3-yl]-5-fluoro-N-[(3S)-3-piperidyl]pyrimidin-4-amine, 1c, (0.16 g, 0.32 mmol) in 1,2-dichloroethane (2 mL) was added 1H-imidazole-2-carbaldehyde (0.03 g, 0.36 mmol) followed by 2 drops of acetic acid and Na(OAc)3BH (0.10 g, 0.49 mmol). The reaction mixture was heated at 60° C. for 18 h. The mixture was cooled to room temperature and diluted with aqueous saturated NaHCO3 solution. The aqueous phase was extracted twice with EtOAc. The combined organic phases were dried (MgSO4), filtered and concentrated in vacuo. The crude residue was purified via silica gel chromatography (0-20% MeOH/CH2Cl2) to afford the product, 4a.

後処理

  1. temperatureThe mixture was cooled to room temperature
  2. extractionThe aqueous phase was extracted twice with EtOAc
  3. dry with materialThe combined organic phases were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude residue was purified via silica gel chromatography (0-20% MeOH/CH2Cl2)

出典と根拠

ORDレコード
ord-d52e158efc06453da4cc711ff06912c4
出典データセット
uspto-grants-2014_09
特許番号
US08829007B2

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