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

HRID 929928Notes

Reaction equation

HRID 929928 reaction equation
[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]

Participants

8

Reactant 4

HCID 674Dimethylamine2×HCID 81531Diisopropylethylamine2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 900238453,5-difluoro-4-(((2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)amino)methyl)benzoic acid

Product 1

HCID 727065293,5-difluoro-4-(((2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)amino)methyl)-N,N-dimethylbenzamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-67c86e2a99834d2899476882da0834cf
Source dataset
uspto-grants-2016_03
Patent number
US09296725B2

Reaction notes

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