(1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanamine hydrochloride → 1-((1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-3-(4-(1,3-dihydroxy-2-methylpropan-2-yl)-3-fluorophenyl)urea

HRID 1842967Notes

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.[OH:20][CH2:21][C:22]([C:26]1[CH:31]=[CH:30][C:29]([NH:32][C:33](=O)[O:34]C2C=CC=CC=2)=[CH:28][C:27]=1[F:42])([CH3:25])[CH2:23][OH:24]>CN(C=O)C>[Cl:2][C:3]1[CH:4]=[C:5]([N:9]2[C:13]([CH2:14][NH:15][C:33]([NH:32][C:29]3[CH:30]=[CH:31][C:26]([C:22]([CH3:25])([CH2:21][OH:20])[CH2:23][OH:24])=[C:27]([F:42])[CH:28]=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

Conditions

Temperature: 50 °C

Procedure

To a stirred solution of (1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanamine hydrochloride (195 mg, 0.62 mmol, 1.0 eq) in DMF (10 mL) was added TEA (190 mg, 1.24 mmol, 2.0 eq) followed by phenyl 4-(1,3-dihydroxy-2-methylpropan-2-yl)-3-fluorophenylcarbamate (200 mg, 0.62 mmol, 1.0 eq) at RT and the mixture was stirred for 16 h at 50° C. The reaction mixture was concentrated under vacuum and the residue purified by neutral alumina column chromatography using MeOH/CHCl3 (0.5:9.5) as eluent to get 1-((1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-3-(4-(1,3-dihydroxy-2-methylpropan-2-yl)-3-fluorophenyl)urea (170 mg; 54%) as a white solid (TLC system: MeOH/CHCl3 (1:9); Rf: 0.45).

Workup

concentrationThe reaction mixture was concentrated under vacuum
customthe residue purified by neutral alumina column chromatography

Sources & evidence

ORD record: ord-e30ffeba12744be380b8570cf597b4a5
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08946204B2

Reaction notes

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