(1-(3-chloro-2-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanamine hydrochloride → 1-((1-(3-chloro-2-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-3-(3-fluoro-4-(hydroxymethyl)phenyl)urea

HRID 1842893Notes

Reaction equation

HRID 1842893 reaction equation
Cl.[Cl:2][C:3]1[C:4]([O:20][CH3:21])=[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:22][C:23]1[CH:24]=[C:25]([NH:31][C:32](=O)[O:33]C2C=CC=CC=2)[CH:26]=[CH:27][C:28]=1[CH2:29][OH:30]>C(Cl)Cl.O>[Cl:2][C:3]1[C:4]([O:20][CH3:21])=[C:5]([N:9]2[C:13]([CH2:14][NH:15][C:32]([NH:31][C:25]3[CH:26]=[CH:27][C:28]([CH2:29][OH:30])=[C:23]([F:22])[CH:24]=3)=[O:33])=[CH:12][C:11]([C:16]([F:18])([F:19])[F:17])=[N:10]2)[CH:6]=[CH:7][CH:8]=1

Participants

5

Reactant 2

HCID 70816406(1-(3-chloro-2-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanamine hydrochlorideHCID 86672140Phenyl (3-fluoro-4-(hydroxymethyl)phenyl)carbamate

Product 1

HCID 708164171-((1-(3-chloro-2-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-3-(3-fluoro-4-(hydroxymethyl)phenyl)ureaYield 61.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (1-(3-chloro-2-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanamine hydrochloride (100 mg, 0.38 mmol, 1.0 eq) in DCM (5 mL) was added TEA (0.16 mL, 1.14 mmol, 3.0 eq) followed by phenyl 3-fluoro-4-(hydroxymethyl)phenyl-carbamate (131 mg, 0.38 mmol, 1.0 eq) at RT and stirred for 16 h. The reaction mixture was diluted with water (15 mL), extracted with DCM (2×15 mL). The combined organic layer was washed with brine (15 mL), dried over anhydrous Na2SO4 and evaporated under vacuum. Crude product was purified by CC to get 1-((1-(3-chloro-2-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-3-(3-fluoro-4-(hydroxymethyl)phenyl)urea (110 mg; 61%) as off white solid (TLC system: MeOH/CHCl3 (1:9); Rf: 0.55).

Workup

  1. extractionextracted with DCM (2×15 mL)
  2. washThe combined organic layer was washed with brine (15 mL)
  3. dry with materialdried over anhydrous Na2SO4
  4. customevaporated under vacuum
  5. customCrude product was purified by CC

Sources & evidence

ORD record
ord-14a7354c6b4d4d88a6c6ad52197177bd
Source dataset
uspto-grants-2015_02
Patent number
US08946204B2

Reaction notes

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