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

HRID 1842934Notes

Reaction equation

HRID 1842934 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([CH2:10][NH2:11])[N:7]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[F:19][C:20]1[CH:21]=[C:22]([CH:31]([CH3:35])[C:32](O)=[O:33])[CH:23]=[CH:24][C:25]=1[CH2:26][O:27][CH2:28][CH2:29][OH:30].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:1]([C:5]1[CH:9]=[C:8]([CH2:10][NH:11][C:32](=[O:33])[CH:31]([C:22]2[CH:23]=[CH:24][C:25]([CH2:26][O:27][CH2:28][CH2:29][OH:30])=[C:20]([F:19])[CH:21]=2)[CH3:35])[N:7]([C:12]2[CH:13]=[CH:14][C:15]([F:18])=[CH:16][CH:17]=2)[N:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 70815722(3-tert-butyl-1-(4-fluorophenyl)-1H-pyrazol-5-yl)methanamineHCID 708158662-(3-Fluoro-4-((2-hydroxyethoxy)methyl)phenyl)propanoic acid

Product 1

HCID 70816374N-((3-tert-butyl-1-(4-fluorophenyl)-1H-pyrazol-5-yl)methyl)-2-(3-fluoro-4-((2-hydroxyethoxy)methyl)phenyl)propanamideYield 78.9%

Reagents, catalysts & solvents 1

HCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

To a stirred solution of (3-tert-butyl-1-(4-fluorophenyl)-1H-pyrazol-5-yl)methanamine (60 mg, 0.25 mmol, 1.0 eq) in THF/DMF (1/20, v/v, 2 mL) was added 2-(3-fluoro-4-((2-hydroxyethoxy)methyl)phenyl)propanoic acid (61 mg, 0.25 mmol, 1 equiv.), HOBt (35 mg. 0.25 mmol, 1 equiv.), TBTU (80 mg, 0.25 mmo, 1 equiv.) and DIPEA (0.168 mL, 127 mg, 1.01 mmol, 4 equiv.) and the mixture was stirred for 3 d at room temperature. 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-(4-fluorophenyl)-1H-pyrazol-5-yl)methyl)-2-(3-fluoro-4-((2-hydroxyethoxy)methyl)phenyl)propanamide (93 mg, 78%).

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-f7d96945ba9b4ea5aa81fb9957aa9b1d
Source dataset
uspto-grants-2015_02
Patent number
US08946204B2

Reaction notes

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