1-Hydroxybenzotriazole → N-((2-chloro-6-(trifluoromethyl)pyridin-3-yl)methyl)-2-(3-fluoro-4-(methylsulfonamidomethyl)-phenyl)propanamide

HRID 1428718Notes

Reaction equation

HRID 1428718 reaction equation
[Cl:1][C:2]1[C:7]([CH2:8][NH2:9])=[CH:6][CH:5]=[C:4]([C:10]([F:13])([F:12])[F:11])[N:3]=1.[F:14][C:15]1[CH:16]=[C:17]([CH:27]([CH3:31])[C:28](O)=[O:29])[CH:18]=[CH:19][C:20]=1[CH2:21][NH:22][S:23]([CH3:26])(=[O:25])=[O:24].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>O1CCCC1.CN(C)C=O>[Cl:1][C:2]1[C:7]([CH2:8][NH:9][C:28](=[O:29])[CH:27]([C:17]2[CH:18]=[CH:19][C:20]([CH2:21][NH:22][S:23]([CH3:26])(=[O:24])=[O:25])=[C:15]([F:14])[CH:16]=2)[CH3:31])=[CH:6][CH:5]=[C:4]([C:10]([F:11])([F:12])[F:13])[N:3]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 72208426(2-Chloro-6-(trifluoromethyl)pyridin-3-YL)methanamineHCID 866793652-(3-Fluoro-4-(methylsulfonamidomethyl)phenyl)propanoic acid

Product 1

HCID 86679935N-((2-chloro-6-(trifluoromethyl)pyridin-3-yl)methyl)-2-(3-fluoro-4-(methylsulfonamidomethyl)-phenyl)propanamideYield 61.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of (2-chloro-6-(trifluoromethyl)pyridin-3-yl)methanamine (2.9 g, 13.8 mmol) and 2-(3-fluoro-4-(methylsulfonamidomethyl)phenyl)propanoic acid (3.8 g, 13.8 mmol) in tetrahydrofuran (100 mL) were added 1-hydroxybenzotriazol (1.89 mL, 13.8 mmol), O-(1H-benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (4.4 g, 13.8 mmol) and N-ethyldiisopropylamine (7 mL, 41.4 mmol) to gave an suspension. After addition of N,N-dimethylformamide (1 mL) the reaction mixture was stirred for 36 h at room temperature. The reaction mixture was concentrated under reduced pressure and the solid obtained was purified by column chromatography (silica gel: 100-200 mesh, eluent: cyclohexane/ethyl acetate 1:2) to afford N-((2-chloro-6-(trifluoromethyl)pyridin-3-yl)methyl)-2-(3-fluoro-4-(methylsulfonamidomethyl)phenyl)propanamide (3.96 g, 61%).

Workup

  1. customto gave an suspension
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. customthe solid obtained
  4. customwas purified by column chromatography (silica gel: 100-200 mesh, eluent: cyclohexane/ethyl acetate 1:2)

Sources & evidence

ORD record
ord-efe60825561c4424b75e4f4e606abebc
Source dataset
uspto-grants-2015_01
Patent number
US08937092B2

Reaction notes

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