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

HRID 1050144Notes

Reaction equation

HRID 1050144 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]([CH2:31][C:32]([CH3:36])([CH3:35])[CH2:33][OH:34])=[C:27]([C:37]([F:40])([F:39])[F:38])[CH:26]=3)=[O:23])=[CH:17][C:16]=2[F:41])=[C:11]([O:42][CH2:43][CH3:44])[CH:10]=1)C1C=CC=CC=1>CO.[Pd]>[CH2:43]([O:42][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]([CH2:31][C:32]([CH3:35])([CH3:36])[CH2:33][OH:34])=[C:27]([C:37]([F:39])([F:40])[F:38])[CH:26]=3)=[O:23])=[CH:17][C:16]=2[F:41])=[CH:13][NH:14][C:9](=[O:8])[CH:10]=1)[CH3:44]

Participants

4

Reactant 1

HCID 904232742-(4-(6-(benzyloxy)-4-ethoxypyridin-3-yl)-3-fluorophenyl)-N-(4-(3-hydroxy-2,2-dimethylpropyl)-3-(trifluoromethyl)phenyl)acetamide

Product 1

HCID 784270272-[4-(4-ethoxy-6-oxo-1H-pyridin-3-yl)-3-fluorophenyl]-N-[4-(3-hydroxy-2,2-dimethylpropyl)-3-(trifluoromethyl)phenyl]acetamideYield 61%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

To a mixture of 2-(4-(6-(benzyloxy)-4-ethoxypyridin-3-yl)-3-fluorophenyl)-N-(4-(3-hydroxy-2,2-dimethylpropyl)-3-(trifluoromethyl)phenyl)acetamide (4.2 g, 6.88 mmol) in MeOH (50 mL) was added Pd/C (10%, 420 mg). The mixture was stirred under H2 at 25° C. for 16 h. Then the reaction residue was filtered and concentrated. The crude material was purified by preparative HPLC (MeCN/H2O as eluants, acidic condition) to yield a white solid of 2-(4-(4-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-3-fluorophenyl)-N-(4-(3-hydroxy-2,2-dimethylpropyl)-3-(trifluoromethyl)phenyl)acetamide (2000.18 mg, 3.84 mmol, 61% yield). TLC (DCM/MeOH=10:1, Rf=0.6): 1H NMR (400 MHz, CD3OD) δ 7.94 (s, 1H), 7.77-7.68 (m, 2H), 7.42 (d, J=8.8 Hz, 1H), 7.37-7.29 (m, 1H), 7.27-7.17 (m, 2H), 6.36 (s., 1H), 4.25-4.15 (m, 2H), 3.75 (s, 2H), 2.76 (s, 2H), 1.33 (t, J=6.8 Hz, 3H), 0.82 (s, 6H); ES-LCMS m/z 521.2 (M+H).

Workup

  1. filtrationThen the reaction residue was filtered
  2. concentrationconcentrated
  3. customThe crude material was purified by preparative HPLC (MeCN/H2O as eluants, acidic condition)

Sources & evidence

ORD record
ord-de5d3fe92f644b49b6a4dcc43e9ee769
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

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