(1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanamine hydrochloride → 1-((1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-3-(3-fluoro-4-(3-hydroxyazetidin-1-yl)phenyl)urea

HRID 1842996Notes

Reaction equation

HRID 1842996 reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[C:5]([N:9]2[C:13]([CH2:14][NH2:15])=[CH:12][C:11]([C:16]([F:19])([F:18])[F:17])=[N:10]2)[CH:6]=[CH:7][CH:8]=1.[F:20][C:21]1[CH:22]=[C:23]([NH:32][C:33](=O)[O:34]C2C=CC=CC=2)[CH:24]=[CH:25][C:26]=1[N:27]1[CH2:30][CH:29]([OH:31])[CH2:28]1>C(Cl)Cl.O>[Cl:2][C:3]1[CH:4]=[C:5]([N:9]2[C:13]([CH2:14][NH:15][C:33]([NH:32][C:23]3[CH:24]=[CH:25][C:26]([N:27]4[CH2:28][CH:29]([OH:31])[CH2:30]4)=[C:21]([F:20])[CH:22]=3)=[O:34])=[CH:12][C:11]([C:16]([F:17])([F:18])[F:19])=[N:10]2)[CH:6]=[CH:7][CH:8]=1

Participants

5

Reactant 2

HCID 70816151(1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanamine hydrochlorideHCID 86672171Phenyl 3-fluoro-4-(3-hydroxyazetidin-1-yl)phenylcarbamate

Product 1

HCID 708155821-((1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-3-(3-fluoro-4-(3-hydroxyazetidin-1-yl)phenyl)ureaYield 63%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanamine hydrochloride (103 mg, 0.33 mmol, 1.0 eq) in DCM (10 mL) was added TEA (0.10 mL, 0.66 mmol, 2.0 eq) followed by phenyl 3-fluoro-4-(3-hydroxyazetidin-1-yl)phenylcarbamate (100 mg, 0.33 mmol, 1.0 eq) at RT and stirred for 48 h. The reaction mixture was diluted with water (5 mL) and extracted with DCM (20 mL), washed with brine, dried over Na2SO4 and evaporated. The residue was purified by CC using 1.0% MeOH in EtOAc as eluent to obtain 1-((1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-3-(3-fluoro-4-(3-hydroxyazetidin-1-yl)phenyl)urea (100 mg; 63%, light brown solid) (TLC: EtOAc/PE 3:2; Rf: 0.3).

Workup

  1. extractionextracted with DCM (20 mL)
  2. washwashed with brine
  3. dry with materialdried over Na2SO4
  4. customevaporated
  5. customThe residue was purified by CC

Sources & evidence

ORD record
ord-5a513cc7c39446bbb3d58e8eaaf35fd4
Source dataset
uspto-grants-2015_02
Patent number
US08946204B2

Reaction notes

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