N-(4-(2-(benzyloxy)ethoxy)-3-(trifluoromethyl)phenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2,6-difluorophenyl)acetamide → 2-[4-(5-ethoxy-6-oxo-1H-pyridin-3-yl)-2,6-difluorophenyl]-N-[4-(2-hydroxyethoxy)-3-(trifluoromethyl)phenyl]acetamide

HRID 576200Notes

Reaction equation

HRID 576200 reaction equation
C([O:8][CH2:9][CH2:10][O:11][C:12]1[CH:17]=[CH:16][C:15]([NH:18][C:19](=[O:48])[CH2:20][C:21]2[C:26]([F:27])=[CH:25][C:24]([C:28]3[CH:29]=[N:30][C:31]([O:37]CC4C=CC(OC)=CC=4)=[C:32]([O:34][CH2:35][CH3:36])[CH:33]=3)=[CH:23][C:22]=2[F:47])=[CH:14][C:13]=1[C:49]([F:52])([F:51])[F:50])C1C=CC=CC=1>CO.[Pd]>[CH2:35]([O:34][C:32]1[C:31](=[O:37])[NH:30][CH:29]=[C:28]([C:24]2[CH:25]=[C:26]([F:27])[C:21]([CH2:20][C:19]([NH:18][C:15]3[CH:16]=[CH:17][C:12]([O:11][CH2:10][CH2:9][OH:8])=[C:13]([C:49]([F:50])([F:52])[F:51])[CH:14]=3)=[O:48])=[C:22]([F:47])[CH:23]=2)[CH:33]=1)[CH3:36]

Participants

4

Reactant 1

HCID 90416829N-(4-(2-(benzyloxy)ethoxy)-3-(trifluoromethyl)phenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2,6-difluorophenyl)acetamide

Product 1

HCID 784264712-[4-(5-ethoxy-6-oxo-1H-pyridin-3-yl)-2,6-difluorophenyl]-N-[4-(2-hydroxyethoxy)-3-(trifluoromethyl)phenyl]acetamideYield 14.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A solution of N-(4-(2-(benzyloxy)ethoxy)-3-(trifluoromethyl)phenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2,6-difluorophenyl)acetamide (70 mg, 0.097 mmol) and Pd/C (10.31 mg, 0.097 mmol) in MeOH (10 mL) was stirred 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 2-(4-(5-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2,6-difluorophenyl)-N-(4-(2-hydroxyethoxy)-3-(trifluoromethyl)phenyl)acetamide (7 mg, 0.014 mmol, 14.0% yield): 1H NMR (400 MHz, CD3OD) δ 7.83 (d, J=2.4 Hz, 1H), 7.71 (d, J=6.8 Hz, 1H), 7.36 (d, J=2.0 Hz, 1H), 7.24 (dd, J=3.0, 5.4 Hz, 3H), 7.16 (d, J=9.0 Hz, 1H), 4.07-4.20 (m, 4H), 3.87 (t, J=5.0 Hz, 2H), 3.81 (s, 2H), 1.46 (t, J=7.06 Hz, 3H); ES-LCMS m/z 513.1 (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-e22ba28a976b404db64cee1659f0be52
Source dataset
uspto-grants-2015_05
Patent number
US09035063B2

Reaction notes

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