[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]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.
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