N-(4-(2-(benzyloxy)ethoxy)-3-(trifluoromethyl)phenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2,3-difluorophenyl)acetamide → 2-(4-(5-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2,3-difluorophenyl)-N-(4-(2-hydroxy ethoxy)-3-(trifluoromethyl)phenyl)acetamide

HRID 1050039Notes

Reaction equation

HRID 1050039 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[CH:26]=[CH:25][C:24]([C:27]3[CH:28]=[N:29][C:30]([O:36]CC4C=CC(OC)=CC=4)=[C:31]([O:33][CH2:34][CH3:35])[CH:32]=3)=[C:23]([F:46])[C:22]=2[F:47])=[CH:14][C:13]=1[C:49]([F:52])([F:51])[F:50])C1C=CC=CC=1>CO.[Pd]>[CH2:34]([O:33][C:31]1[C:30](=[O:36])[NH:29][CH:28]=[C:27]([C:24]2[CH:25]=[CH:26][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:52])([F:50])[F:51])[CH:14]=3)=[O:48])=[C:22]([F:47])[C:23]=2[F:46])[CH:32]=1)[CH3:35]

Participants

4

Reactant 1

HCID 90416445N-(4-(2-(benzyloxy)ethoxy)-3-(trifluoromethyl)phenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2,3-difluorophenyl)acetamide

Product 1

HCID 784263332-(4-(5-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2,3-difluorophenyl)-N-(4-(2-hydroxy ethoxy)-3-(trifluoromethyl)phenyl)acetamideYield 44.7%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a solution of N-(4-(2-(benzyloxy)ethoxy)-3-(trifluoromethyl)phenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2,3-difluorophenyl)acetamide (10 mg, 0.014 mmol) in MeOH (3 mL) stirred under N2 at 20° C. was added Pd/C (0.147 mg, 1.384 μmol) in one charge. The solution was stirred under a H2 atmosphere. The reaction mixture was stirred at 10° C. for 12 h. The mixture was filtered, and the filtrate was concentrated in vacuo to give the crude product. The crude material was purified by preparative HPLC (MeCN/H2O as eluants, acidic condition) to yield a light yellow solid of 2-(4-(5-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2,3-difluorophenyl)-N-(4-(2-hydroxy ethoxy)-3-(trifluoromethyl)phenyl)acetamide (3.17 mg, 6.19 μmol, 44.7% yield). TLC (DCM/MeOH=5:1, Rf=0.4): 1H NMR (400 MHz, CD3OD) δ 7.88 (d, J=2.4 Hz, 1H), 7.75 (dd, J=2.2, 8.8 Hz, 1H), 7.37-7.12 (m, 5H), 4.20-4.07 (m, 4H), 3.90 (t, J=5.0 Hz, 2H), 3.85 (s, 2H), 1.48 (t, J=7.0 Hz, 3H); ES-LCMS m/z 513.2 (M+H).

Workup

  1. additioncharge
  2. stirringThe reaction mixture was stirred at 10° C. for 12 h
  3. filtrationThe mixture was filtered
  4. concentrationthe filtrate was concentrated in vacuo
  5. customto give the crude product
  6. customThe crude material was purified by preparative HPLC (MeCN/H2O as eluants, acidic condition)

Sources & evidence

ORD record
ord-1f3cdb551a7347c1a62e89b563795fc8
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

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