3-(Trifluoromethyl)aniline → 2-[4-(4-ethoxy-6-oxo-1H-pyridin-3-yl)-2-fluorophenyl]-N-[3-(trifluoromethyl)phenyl]acetamide

HRID 1050146Notes

Reaction equation

HRID 1050146 reaction equation
[CH2:1]([O:3][C:4]1[C:5]([C:11]2[CH:16]=[CH:15][C:14]([CH2:17][C:18]([OH:20])=O)=[C:13]([F:21])[CH:12]=2)=[CH:6][NH:7][C:8](=[O:10])[CH:9]=1)[CH3:2].[F:22][C:23]([F:32])([F:31])[C:24]1[CH:25]=[C:26]([CH:28]=[CH:29][CH:30]=1)[NH2:27].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH2:1]([O:3][C:4]1[C:5]([C:11]2[CH:16]=[CH:15][C:14]([CH2:17][C:18]([NH:27][C:26]3[CH:28]=[CH:29][CH:30]=[C:24]([C:23]([F:22])([F:31])[F:32])[CH:25]=3)=[O:20])=[C:13]([F:21])[CH:12]=2)=[CH:6][NH:7][C:8](=[O:10])[CH:9]=1)[CH3:2]

Participants

6

Reactant 4

HCID 73753-(Trifluoromethyl)anilineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 904228612-(4-(4-Ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)acetic acid

Product 1

HCID 784271682-[4-(4-ethoxy-6-oxo-1H-pyridin-3-yl)-2-fluorophenyl]-N-[3-(trifluoromethyl)phenyl]acetamideYield 12%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-(4-(4-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)acetic acid (80 mg, 0.275 mmol), 3-(trifluoromethyl)aniline (44.3 mg, 0.275 mmol), HATU (125 mg, 0.330 mmol) and DIEA (0.048 mL, 0.275 mmol) in DMF (10 mL) was stirred at rt for 5 h. After LCMS analysis showed the starting material had disappeared, the reaction mixture was concentrated under reduced pressure. The residue was dissolved in DCM and washed with H2O and brine. The organic layer was evaporated to dryness to give crude product which was purified by preparative HPLC to give pure product 2-(4-(4-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)-N-(3-(trifluoromethyl)phenyl)acetamide (14.56 mg, 0.032 mmol, 12% yield) as a yellow solid. 1H NMR (400 MHz, CD3OD): δ 8.03 (br. s., 1H), 7.77 (d, J=8.2 Hz, 1H), 7.69 (s, 1H), 7.51 (t, J=8.0 Hz, 1H), 7.46-7.36 (m, 2H), 7.31-7.24 (m, 2H), 6.28 (s, 1H), 4.24-4.19 (m, 2H), 3.84 (s, 2H), 1.41 (t, J=6.8 Hz, 3H); ES-LCMS: m/z 435.1 (M+H).

Workup

  1. concentrationthe reaction mixture was concentrated under reduced pressure
  2. dissolutionThe residue was dissolved in DCM
  3. washwashed with H2O and brine
  4. customThe organic layer was evaporated to dryness
  5. customto give crude product which
  6. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-f5ab9ebf699245c0af44b1c3be14f81f
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

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