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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
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HRID 74868 반응식
[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
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7

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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-amine2회

생성물 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

시약·촉매·용매 3

HCID 176
Acetic Acid
촉매
HCID 111,2-Dichloroethane용매
HCID 516892Sodium Bicarbonate용매

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온도
60 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-d52e158efc06453da4cc711ff06912c4
출처 데이터셋
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08829007B2

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