1-Hydroxybenzotriazole → N-((3-tert-butyl-1-(3-(trifluoromethoxy)phenyl)-1H-pyrazol-5-yl)methyl)-2-(3-fluoro-4-((2-hydroxyethoxy)methyl)phenyl)propanamide

HRID 1842936Notes

Reaction equation

HRID 1842936 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][CH:16]=[C:15]([O:19][C:20]([F:23])([F:22])[F:21])[CH:14]=2)[N:7]=1)([CH3:5])([CH3:4])[CH3:3].[F:24][C:25]1[CH:26]=[C:27]([CH:36]([CH3:40])[C:37](O)=[O:38])[CH:28]=[CH:29][C:30]=1[CH2:31][O:32][CH2:33][CH2:34][OH:35].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>[C:2]([C:6]1[CH:10]=[C:9]([CH2:11][NH:12][C:37](=[O:38])[CH:36]([C:27]2[CH:28]=[CH:29][C:30]([CH2:31][O:32][CH2:33][CH2:34][OH:35])=[C:25]([F:24])[CH:26]=2)[CH3:40])[N:8]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([O:19][C:20]([F:22])([F:23])[F:21])[CH:14]=2)[N:7]=1)([CH3:5])([CH3:3])[CH3:4]

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 70816542(3-tert-butyl-1-(3-(trifluoromethoxy)phenyl)-1H-pyrazol-5-yl)methanamine hydrochloride

Product 1

HCID 70815249N-((3-tert-butyl-1-(3-(trifluoromethoxy)phenyl)-1H-pyrazol-5-yl)methyl)-2-(3-fluoro-4-((2-hydroxyethoxy)methyl)phenyl)propanamideYield 73%

Reagents, catalysts & solvents 1

HCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

To a stirred solution of (3-tert-butyl-1-(3-(trifluoromethoxy)phenyl)-1H-pyrazol-5-yl)methanamine hydrochloride (119 mg, 0.351 mmol, 1 eq) in THF/DMF (1/20, v/v, 3 mL) was added 2-(3-fluoro-4-((2-hydroxyethoxy)methyl)phenyl)propanoic acid (84 mg, 0.35 mmol, 1 equiv.), HOBt (49 mg. 0.35 mmol, 1 equiv.), TBTU (112 mg, 0.351 mmo, 1 equiv.) and DIPEA (0.234 mL, 178 mg, 1.40 mmol, 4 equiv.) and the mixture was stirred for at room temperature overnight. The reaction mixture was evaporated and the residue was purified by column chromatography (EtOAc/cyclohexane (1:2) as eluent) to give N-((3-tert-butyl-1-(3-(trifluoromethoxy)phenyl)-1H-pyrazol-5-yl)methyl)-2-(3-fluoro-4-((2-hydroxyethoxy)methyl)phenyl)propanamide (137 mg, 73%).

Workup

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

Sources & evidence

ORD record
ord-89045136af5343dabec65e8976e24125
Source dataset
uspto-grants-2015_02
Patent number
US08946204B2

Reaction notes

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