Water → 4-((1-((4-cyano-3-(trifluoromethyl)phenyl)amino)-2-methyl-1-oxopropan-2-yl)amino)-2-fluoro-N-methylbenzamide

HRID 2274373Notes

Reaction equation

HRID 2274373 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:12][C:13]([CH3:18])([CH3:17])[C:14]([OH:16])=O)[CH:5]=[CH:6][C:7]=1[C:8](=[O:11])[NH:9][CH3:10].CCN=C=NCCCN(C)C.Cl.[NH2:31][C:32]1[CH:39]=[CH:38][C:35]([C:36]#[N:37])=[C:34]([C:40]([F:43])([F:42])[F:41])[CH:33]=1.O>C(Cl)Cl>[C:36]([C:35]1[CH:38]=[CH:39][C:32]([NH:31][C:14]([C:13]([NH:12][C:4]2[CH:5]=[CH:6][C:7]([C:8]([NH:9][CH3:10])=[O:11])=[C:2]([F:1])[CH:3]=2)([CH3:18])[CH3:17])=[O:16])=[CH:33][C:34]=1[C:40]([F:41])([F:42])[F:43])#[N:37]

Participants

6

Reactant 4

HCID 962WaterHCID 5221704-Amino-2-(trifluoromethyl)benzonitrileHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 671068972-((3-Fluoro-4-(methylcarbamoyl)phenyl)amino)-2-methylpropanoic acid

Product 1

HCID 671067934-((1-((4-cyano-3-(trifluoromethyl)phenyl)amino)-2-methyl-1-oxopropan-2-yl)amino)-2-fluoro-N-methylbenzamideYield 30.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The title compound was made in accordance with General Method 1. 2-(3-Fluoro-4-methylcarbamoyl-phenylamino)-2-methyl-propionic acid (1.27 g) was dissolved in DCM. EDCI-HCl (1.91 g) was added to it and the reaction mixture was stirred for 5 min at RT. 4-Amino-2-(trifluoromethyl)benzonitrile (1.00 g) was added portionwise and stirring was continued for 5 h at RT. Water was added to the reaction mixture, and the product was extracted with DCM. The combined organic layer was washed with water, dried over sodium sulfate and evaporated under reduced pressure. The residue was purified by silica gel chromatography (100-200 mesh silica gel) eluting with 5% MeOH-DCM to obtain 650 mg of 4-[1-(4-Cyano-3-trifluoromethyl-phenylcarbamoyl)-1-methyl-ethylamino]-2-fluoro-N-methyl-benzamide, HPLC, Column: YMC ODS AQ, 4.6×250 mm, 5 μm, Mobile Phase A:0.05% TFA, Mobile Phase B:ACN, Gradient: 10% to 90% B in 10 min, hold for 10 min, 90% to 10% B in 1 min, Flow Rate: 1 mL/min, Retention time: 11.174 min, M+1: 423.

Workup

  1. stirringstirring
  2. waitwas continued for 5 h at RT
  3. extractionthe product was extracted with DCM
  4. washThe combined organic layer was washed with water
  5. dry with materialdried over sodium sulfate
  6. customevaporated under reduced pressure
  7. customThe residue was purified by silica gel chromatography (100-200 mesh silica gel)
  8. washeluting with 5% MeOH-DCM

Sources & evidence

ORD record
ord-c0ded99315cc4d60ba76a99b99b5a89b
Source dataset
uspto-grants-2015_09
Patent number
US09126962B2

Reaction notes

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