1-Hydroxybenzotriazole → N-((1-(3,5-difluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-2-(3-fluoro-4-((2-hydroxyethoxy)methyl)phenyl)propanamide

HRID 1842939Notes

Reaction equation

HRID 1842939 reaction equation
Cl.[F:2][C:3]1[CH:4]=[C:5]([N:10]2[C:14]([CH2:15][NH2:16])=[CH:13][C:12]([C:17]([F:20])([F:19])[F:18])=[N:11]2)[CH:6]=[C:7]([F:9])[CH:8]=1.[F:21][C:22]1[CH:23]=[C:24]([CH:33]([CH3:37])[C:34](O)=[O:35])[CH:25]=[CH:26][C:27]=1[CH2:28][O:29][CH2:30][CH2:31][OH:32].C1C=CC2N(O)N=NC=2C=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C>C1COCC1.CN(C=O)C>[F:2][C:3]1[CH:4]=[C:5]([N:10]2[C:14]([CH2:15][NH:16][C:34](=[O:35])[CH:33]([C:24]3[CH:25]=[CH:26][C:27]([CH2:28][O:29][CH2:30][CH2:31][OH:32])=[C:22]([F:21])[CH:23]=3)[CH3:37])=[CH:13][C:12]([C:17]([F:18])([F:20])[F:19])=[N:11]2)[CH:6]=[C:7]([F:9])[CH:8]=1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 708158662-(3-Fluoro-4-((2-hydroxyethoxy)methyl)phenyl)propanoic acidHCID 86672152(1-(3,5-difluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanamine hydrochloride

Product 1

HCID 86672153N-((1-(3,5-difluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-2-(3-fluoro-4-((2-hydroxyethoxy)methyl)phenyl)propanamide

Reagents, catalysts & solvents 1

HCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

To a stirred solution of (1-(3,5-difluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanamine hydrochloride (16 mg, 0.050 mmol, 1.0 eq) in THF/DMF (1/20, v/v, 0.5 mL) was added 2-(3-fluoro-4-((2-hydroxyethoxy)methyl)phenyl)propanoic acid (11 mg, 0.050 mmol, 1 equiv.), HOBt (7 mg. 0.05 mmol, 1 equiv.), TBTU (16 mg, 0.050 mmo, 1 equiv.) and DIPEA (0.033 mL, 25 mg, 0.20 mmol, 4 equiv.) and the mixture was stirred for at room temperature overnight. The solvent of the reaction mixture was evaporated and the residue was purified by column chromatography (EtOAc/cyclohexane (1:1) as eluent) to give N-((1-(3,5-difluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-2-(3-fluoro-4-((2-hydroxyethoxy)methyl)phenyl)propanamide (23 mg, 92 N.

Workup

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

Sources & evidence

ORD record
ord-e48df7dcaaff47e28500dbb0e7aa047b
Source dataset
uspto-grants-2015_02
Patent number
US08946204B2

Reaction notes

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