(3-tert-butyl-1-(3,4-difluorophenyl)-1H-pyrazol-5-yl)methanamine hydrochloride → 1-((3-tert-butyl-1-(3,4-difluorophenyl)-1H-pyrazol-5-yl)methyl)-3-(3-fluoro-4-(3-hydroxyazetidin-1-yl)phenyl)urea

HRID 1842999Notes

Reaction equation

HRID 1842999 reaction equation
Cl.[C:2]([C:6]1[CH:10]=[C:9]([CH2:11][NH2:12])[N:8]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[C:15]([F:20])[CH:14]=2)[N:7]=1)([CH3:5])([CH3:4])[CH3:3].[F:21][C:22]1[CH:23]=[C:24]([NH:33][C:34](=O)[O:35]C2C=CC=CC=2)[CH:25]=[CH:26][C:27]=1[N:28]1[CH2:31][CH:30]([OH:32])[CH2:29]1>C(#N)C>[C:2]([C:6]1[CH:10]=[C:9]([CH2:11][NH:12][C:34]([NH:33][C:24]2[CH:25]=[CH:26][C:27]([N:28]3[CH2:29][CH:30]([OH:32])[CH2:31]3)=[C:22]([F:21])[CH:23]=2)=[O:35])[N:8]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[C:15]([F:20])[CH:14]=2)[N:7]=1)([CH3:5])([CH3:3])[CH3:4]

Participants

4

Reactant 2

HCID 70816984(3-tert-butyl-1-(3,4-difluorophenyl)-1H-pyrazol-5-yl)methanamine hydrochlorideHCID 86672171Phenyl 3-fluoro-4-(3-hydroxyazetidin-1-yl)phenylcarbamate

Product 1

HCID 708164891-((3-tert-butyl-1-(3,4-difluorophenyl)-1H-pyrazol-5-yl)methyl)-3-(3-fluoro-4-(3-hydroxyazetidin-1-yl)phenyl)ureaYield 46.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of (3-tert-butyl-1-(3,4-difluorophenyl)-1H-pyrazol-5-yl)methanamine hydrochloride (85 mg, 0.282 mmol, 1.0 eq) in acetonitrile (6.7 mL) was added TEA (0.16 mL, 1.1 mmol, 4.0 eq) followed by phenyl 3-fluoro-4-(3-hydroxyazetidin-1-yl)phenylcarbamate (86 mg, 0.287 mmol, 1.02 eq) and stirred at reflux for 16 h. The solvent of the reaction mixture was evaporated and the residue was purified by column chromatography (EtOAc/cyclohexane (1:2) as eluent) to get 1-((3-tert-butyl-1-(3,4-difluorophenyl)-1H-pyrazol-5-yl)methyl)-3-(3-fluoro-4-(3-hydroxyazetidin-1-yl)phenyl)urea (62 mg, 46%).

Workup

  1. temperatureat reflux for 16 h
  2. customThe solvent of the reaction mixture was evaporated
  3. customthe residue was purified by column chromatography (EtOAc/cyclohexane (1:2) as eluent)

Sources & evidence

ORD record
ord-7114ade9ee4c4fa0af9c31645cc49862
Source dataset
uspto-grants-2015_02
Patent number
US08946204B2

Reaction notes

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