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

HRID 59170Notes

Reaction equation

HRID 59170 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:25][C:26]2[N:31]=[C:30]([CH:32]=O)[CH:29]=[C:28]([CH2:34][O:35][CH2:36][C:37]([F:40])([F:39])[F:38])[N:27]=2)[CH:15]=[CH:16][C:17]=1[C:18]1[CH:23]=[C:22]([CH3:24])[N:21]=[N:20][CH:19]=1.C(O)(=O)C.C([BH3-])#N.[Na+]>O.CO>[F:2][CH:3]1[CH2:6][N:5]([CH2:32][C:30]2[CH:29]=[C:28]([CH2:34][O:35][CH2:36][C:37]([F:39])([F:40])[F:38])[N:27]=[C:26]([NH:25][C:14]3[CH:15]=[CH:16][C:17]([C:18]4[CH:23]=[C:22]([CH3:24])[N:21]=[N:20][CH:19]=4)=[C:12]([O:11][CH3:10])[CH:13]=3)[N:31]=2)[CH2:4]1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 101250543-fluoroazetidine HydrochlorideHCID 10942334Sodium MethoxideHCID 1178214562-(3-Methoxy-4-(6-methylpyridazin-4-yl)phenylamino)-6-((2,2,2-trifluoroethoxy)methyl)-pyrimidine-4-carbaldehyde

Product 1

HCID 863453374-((3-Fluoroazetidin-1-yl)methyl)-N-(3-methoxy-4-(6-methylpyridazin-4-yl)phenyl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-2-amine

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

3-Fluoroazetidine hydrochloride (31 mg, 0.28 mmol) was mixed with methanol (5 mL). Sodium methoxide (0.051 mL, 0.28 mmol) was added followed by 2-(3-methoxy-4-(6-methylpyridazin-4-yl)phenylamino)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidine-4-carbaldehyde (100 mg, 0.23 mmol). The mixture was stirred for 2 min. Acetic acid (0.042 mL, 0.74 mmol) was added. The mixture was stirred for 5 min. Sodium cyanoborohydride (20 mg, 0.32 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 solid, 48 mg (42%).

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-1547ffa036b44c2d9a9541b818ad73df
Source dataset
uspto-grants-2016_09
Patent number
US09439904B2

Reaction notes

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