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

HRID 576192Notes

Reaction equation

HRID 576192 reaction equation
C([O:8][C:9]1[N:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][C:18]([CH2:21][C:22]([NH:24][C:25]3[CH:30]=[CH:29][C:28]([C:31]#[N:32])=[C:27]([C:33]([F:36])([F:35])[F:34])[CH:26]=3)=[O:23])=[CH:17][C:16]=2[F:37])=[C:11]([O:38][CH2:39][CH3:40])[CH:10]=1)C1C=CC=CC=1>CO.[Pd]>[C:31]([C:28]1[CH:29]=[CH:30][C:25]([NH:24][C:22](=[O:23])[CH2:21][C:18]2[CH:19]=[CH:20][C:15]([C:12]3[C:11]([O:38][CH2:39][CH3:40])=[CH:10][C:9](=[O:8])[NH:14][CH:13]=3)=[C:16]([F:37])[CH:17]=2)=[CH:26][C:27]=1[C:33]([F:35])([F:36])[F:34])#[N:32]

Participants

4

Reactant 1

HCID 904159812-(4-(6-(benzyloxy)-4-ethoxypyridin-3-yl)-3-fluorophenyl)-N-(4-cyano-3-(trifluoromethyl)phenyl)acetamide

Product 1

HCID 78426470N-[4-cyano-3-(trifluoromethyl)phenyl]-2-[4-(4-ethoxy-6-oxo-1H-pyridin-3-yl)-3-fluorophenyl]acetamideYield 36.2%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A solution of 2-(4-(6-(benzyloxy)-4-ethoxypyridin-3-yl)-3-fluorophenyl)-N-(4-cyano-3-(trifluoromethyl)phenyl)acetamide (12 mg, 0.022 mmol) and Pd/C (2.324 mg, 0.022 mmol) in MeOH (10 mL) was stirred at 20° C. under a H2 atmosphere for 16 h. After LCMS analysis showed the starting material had disappeared, the mixture was filtered. The filtrate was concentrated to give the crude product, which was purified by preparative HPLC to yield a white solid of N-(4-cyano-3-(trifluoromethyl)phenyl)-2-(4-(4-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-3-fluorophenyl)acetamide (3.63 mg, 7.90 μmol, 36.2% yield): 1H NMR (400 MHz, CD3OD) δ 8.23 (s, 1H), 8.02-7.95 (m, 1H), 7.94-7.88 (m, 1H), 7.59 (s, 1H), 7.35-7.29 (m, 1H), 7.25-7.15 (m, 2H), 6.23 (s, 1H), 4.16 (m, 2H), 3.80 (s, 2H), 1.32 (t, J=7.0 Hz, 3H); ES-LCMS m/z 460.1 (M+H).

Workup

  1. filtrationthe mixture was filtered
  2. concentrationThe filtrate was concentrated
  3. customto give the crude product, which
  4. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-272b65eee6694fa297a02f447bbee0a6
Source dataset
uspto-grants-2015_05
Patent number
US09035063B2

Reaction notes

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