2-(4-(6-(benzyloxy)-4-ethoxypyridin-3-yl)-2-fluorophenyl)-N-(4-(2-(benzyloxy) ethoxy)-3-(trifluoromethyl)phenyl)acetamide → 2-(4-(4-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)-N-(4-(2-hydroxyethoxy)-3-(trifluoromethyl)phenyl) acetamide

HRID 576233Notes

Reaction equation

HRID 576233 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]([O:31][CH2:32][CH2:33][O:34]CC4C=CC=CC=4)=[C:27]([C:42]([F:45])([F:44])[F:43])[CH:26]=3)=[O:23])=[C:17]([F:46])[CH:16]=2)=[C:11]([O:47][CH2:48][CH3:49])[CH:10]=1)C1C=CC=CC=1>CO.[Pd]>[CH2:48]([O:47][C:11]1[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]([O:31][CH2:32][CH2:33][OH:34])=[C:27]([C:42]([F:44])([F:45])[F:43])[CH:26]=3)=[O:23])=[C:17]([F:46])[CH:16]=2)=[CH:13][NH:14][C:9](=[O:8])[CH:10]=1)[CH3:49]

Participants

4

Reactant 1

HCID 904184152-(4-(6-(benzyloxy)-4-ethoxypyridin-3-yl)-2-fluorophenyl)-N-(4-(2-(benzyloxy) ethoxy)-3-(trifluoromethyl)phenyl)acetamide

Product 1

HCID 784267482-(4-(4-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)-N-(4-(2-hydroxyethoxy)-3-(trifluoromethyl)phenyl) acetamideYield 38.8%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of 2-(4-(6-(benzyloxy)-4-ethoxypyridin-3-yl)-2-fluorophenyl)-N-(4-(2-(benzyloxy)ethoxy)-3-(trifluoromethyl)phenyl)acetamide (60 mg, 0.089 mmol), Pd/C (9.46 mg, 0.089 mmol) in MeOH (10 mL) was stirred for 16 h under a H2 atmosphere at 25° C. Then the mixture was filtered and the filtrate was concentrated to give the residue which was purified by preparative HPLC to yield 2-(4-(4-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)-N-(4-(2-hydroxyethoxy)-3-(trifluoromethyl)phenyl) acetamide (17.76 mg, 0.034 mmol, 38.8% yield): 1H NMR (400 MHz, CD3OD) δ 7.83 (d, J=2.4 Hz., 1H), 7.73-7.70 (m, 1H), 7.35-7.29 (m, 2H), 7.42 (s, 1H), 7.37 (d, J=8.0 Hz, 1H), 7.23-7.21 (m, 2H), 7.17-7.14 (d, J=4.6 Hz, 1H), 6.03 (s, 1H), 4.13-4.11 (m, 4H), 3.87 (t, J=5.0 Hz, 2H), 3.76 (s, 2H), 1.37 (t, J=7.0 Hz, 3H); ES-LCMS m/z 495 (M+H).

Workup

  1. filtrationThen the mixture was filtered
  2. concentrationthe filtrate was concentrated
  3. customto give the residue which
  4. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-c3357261d68847a08d8a5fa72474e793
Source dataset
uspto-grants-2015_05
Patent number
US09035063B2

Reaction notes

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