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 1050054Notes

Reaction equation

HRID 1050054 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-04ef544d7a9843b585fd08cbe65c771e
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

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