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Dimethylamine → 3,5-difluoro-4-(((2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)amino)methyl)-N,N-dimethylbenzamide

HRID 929928
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HRID 929928 반응식
[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([F:26])[C:10]=1[CH2:11][NH:12][C:13]1[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]2[CH:21]=[N:22][N:23]([CH3:25])[CH:24]=2)[N:14]=1)[C:5](O)=[O:6].[CH3:27][N:28](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)[CH3:29].F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.CNC>C(#N)C.O.CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([F:26])[C:10]=1[CH2:11][NH:12][C:13]1[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]2[CH:21]=[N:22][N:23]([CH3:25])[CH:24]=2)[N:14]=1)[C:5]([N:28]([CH3:29])[CH3:27])=[O:6]
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참가 물질

8

반응물 4

HCID 674Dimethylamine2회HCID 81531Diisopropylethylamine2회HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2회HCID 900238453,5-difluoro-4-(((2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)amino)methyl)benzoic acid

생성물 1

HCID 72706529
3,5-difluoro-4-(((2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)amino)methyl)-N,N-dimethylbenzamide

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 6342Acetonitrile용매

실험 절차

A mixture of 3,5-difluoro-4-(((2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)amino)methyl)benzoic acid (crude from step i, theoretical 60 mg, 0.17 mmol), HATU (82 mg, 0.22 mmol), DIPEA (43 mg, 0.33 mmol) and dimethylamine (excess) in acetonitrile (10 mL) was stirred at room temperature overnight then further DMF, HATU, DIPEA and dimethylamine were added to push the reaction to completion. After 5 h the reaction was diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, concentrated in vacuo and purified by prep. TLC (10% v/v MeOH/DCM) to afford 3,5-difluoro-4-(((2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)amino)methyl)-N,N-dimethylbenzamide I-7 (30 mg, 0.07 mmol) as a white solid. LC-MS (Method A), RT=7.79 min. (ES+) 388.

후처리

  1. customthe reaction to completion
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. concentrationconcentrated in vacuo
  5. custompurified by prep

출처 및 근거

ORD 기록
ord-67c86e2a99834d2899476882da0834cf
출처 데이터셋
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09296725B2

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