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 1050062Notes

Reaction equation

HRID 1050062 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-b3aa178b9c204876b50cbbe1f0c07dbc
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

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