1-Hydroxybenzotriazole → N-[[2-(3-chlorophenyl)-5-(trifluoromethyl)-2H-pyrazol-3-yl]-methyl]-2-(3-fluoro-4-methylsulfonyl-phenyl)-propionamide

HRID 1843008Notes

Reaction equation

HRID 1843008 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:12]([CH3:16])[C:13]([OH:15])=O)[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].ON1C2C=CC=CC=2N=N1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C.[Cl:58][C:59]1[CH:60]=[C:61]([N:65]2[C:69]([CH2:70][NH2:71])=[CH:68][C:67]([C:72]([F:75])([F:74])[F:73])=[N:66]2)[CH:62]=[CH:63][CH:64]=1>C1COCC1>[Cl:58][C:59]1[CH:60]=[C:61]([N:65]2[C:69]([CH2:70][NH:71][C:13](=[O:15])[CH:12]([C:4]3[CH:5]=[CH:6][C:7]([S:8]([CH3:11])(=[O:9])=[O:10])=[C:2]([F:1])[CH:3]=3)[CH3:16])=[CH:68][C:67]([C:72]([F:73])([F:74])[F:75])=[N:66]2)[CH:62]=[CH:63][CH:64]=1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 66644230(1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanamineHCID 708157452-(3-Fluoro-4-(methylsulfonyl)phenyl)propanoic acid

Product 1

HCID 70816186N-[[2-(3-chlorophenyl)-5-(trifluoromethyl)-2H-pyrazol-3-yl]-methyl]-2-(3-fluoro-4-methylsulfonyl-phenyl)-propionamideYield 76%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-(3-fluoro-4-(methylsulfonyl)phenyl)propanoic acid (60 mg, 0.244 mmol) in THF (1.9 mL) was added 1-hydroxybenzotriazole (32 mg, 0.244 mmol), O-(1H-benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (78 mg, 0.244 mmol), N-ethyldiisopropylamine (0.083 mL, 0.488 mmol) and (1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanamine (67 mg, 0.244 mmol). The solution was stirred for 48 h at room temperature. The reaction mixture was concentrated in vacuo and purified by column chromatography (ethyl acetate/cyclohexane (2:1)) to give pure N-[[2-(3-chlorophenyl)-5-(trifluoromethyl)-2H-pyrazol-3-yl]-methyl]-2-(3-fluoro-4-methylsulfonyl-phenyl)-propionamide (example compound D2) (93 mg, 76%).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. custompurified by column chromatography (ethyl acetate/cyclohexane (2:1))

Sources & evidence

ORD record
ord-cf189e74d22d4d5e8dfeb2d511f1c659
Source dataset
uspto-grants-2015_02
Patent number
US08946204B2

Reaction notes

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