Acetic Acid → 4-((3-Fluoroazetidin-1-yl)methyl)-N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-2-amine

HRID 59168Notes

Reaction equation

HRID 59168 reaction equation
Cl.[F:2][CH:3]1[CH2:6][NH:5][CH2:4]1.C[O-].[Na+].[CH3:10][O:11][C:12]1[CH:13]=[C:14]([NH:24][C:25]2[N:30]=[C:29]([CH:31]=O)[CH:28]=[C:27]([CH2:33][O:34][CH2:35][C:36]([F:39])([F:38])[F:37])[N:26]=2)[CH:15]=[CH:16][C:17]=1[N:18]1[CH:22]=[C:21]([CH3:23])[N:20]=[CH:19]1.C(O)(=O)C.C([BH3-])#N.[Na+]>O.CO>[F:2][CH:3]1[CH2:6][N:5]([CH2:31][C:29]2[CH:28]=[C:27]([CH2:33][O:34][CH2:35][C:36]([F:38])([F:39])[F:37])[N:26]=[C:25]([NH:24][C:14]3[CH:15]=[CH:16][C:17]([N:18]4[CH:22]=[C:21]([CH3:23])[N:20]=[CH:19]4)=[C:12]([O:11][CH3:10])[CH:13]=3)[N:30]=2)[CH2:4]1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 101250543-fluoroazetidine HydrochlorideHCID 10942334Sodium MethoxideHCID 1178240362-(3-Methoxy-4-(4-methyl-1H-imidazol-1-yl)phenylamino)-6-((2,2,2-trifluoroethoxy)methyl)-pyrimidine-4-carbaldehyde

Product 1

HCID 863425654-((3-Fluoroazetidin-1-yl)methyl)-N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-2-amine

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

3-Fluoroazetidine hydrochloride (25 mg, 0.23 mmol) was mixed with methanol (5 mL). Sodium methoxide (30 w % in methanol, 0.042 mL, 0.23 mmol) was added followed by 2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenylamino)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidine-4-carbaldehyde (80 mg, 0.19 mmol). The mixture was stirred for 2 min. Acetic acid (0.035 mL, 0.61 mmol) was added and the mixture was stirred for 5 min. Sodium cyanoborohydride (17 mg, 0.27 mmol) was added and the mixture was stirred at rt under nitrogen atmosphere for 1 h. Water was added and the mixture was stirred for 5 min. The solvents were evaporated and the residue was purified by preparative HPLC to give the title compound as a dry film 44 mg (48%).

Workup

  1. stirringthe mixture was stirred for 5 min
  2. stirringthe mixture was stirred at rt under nitrogen atmosphere for 1 h
  3. stirringthe mixture was stirred for 5 min
  4. customThe solvents were evaporated
  5. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-c99366cedae44ac490f79028b8fc85ae
Source dataset
uspto-grants-2016_09
Patent number
US09439904B2

Reaction notes

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