N-(3-(2-(dimethylamino)ethoxy)-5-(trifluoromethyl)phenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)ace tamide → N-[3-[2-(dimethylamino)ethoxy]-5-(trifluoromethyl)phenyl]-2-[4-(5-ethoxy-6-oxo-1H-pyridin-3-yl)-2-fluorophenyl]acetamide

HRID 1050198Notes

Reaction equation

HRID 1050198 reaction equation
[CH3:1][N:2]([CH3:46])[CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]([NH:16][C:17](=[O:45])[CH2:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:26]=[N:27][C:28]([O:34]CC4C=CC(OC)=CC=4)=[C:29]([O:31][CH2:32][CH3:33])[CH:30]=3)=[CH:21][C:20]=2[F:44])[CH:9]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:11]=1>CO.[Pd]>[CH3:46][N:2]([CH3:1])[CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]([NH:16][C:17](=[O:45])[CH2:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:30]=[C:29]([O:31][CH2:32][CH3:33])[C:28](=[O:34])[NH:27][CH:26]=3)=[CH:21][C:20]=2[F:44])[CH:9]=[C:10]([C:12]([F:15])([F:13])[F:14])[CH:11]=1

Participants

4

Reactant 1

HCID 90422426N-(3-(2-(dimethylamino)ethoxy)-5-(trifluoromethyl)phenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)ace tamide

Product 1

HCID 78427432N-[3-[2-(dimethylamino)ethoxy]-5-(trifluoromethyl)phenyl]-2-[4-(5-ethoxy-6-oxo-1H-pyridin-3-yl)-2-fluorophenyl]acetamideYield 50.6%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a suspension of N-(3-(2-(dimethylamino)ethoxy)-5-(trifluoromethyl)phenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetamide (100 mg, 0.156 mmol) in MeOH (10 mL) was added Pd/C (16.59 mg, 0.156 mmol). The mixture was hydrogenated at 26° C. for 3 h under a H2 atmosphere. Then the solution was filtered and concentrated to give the residue. The crude material was purified by preparative HPLC (Instrument: Gilson GX281/Column: Gemini 150*25 mm*5 um/Mobile phase A: Water (0.05% ammonia solution)/Mobile phaseB: Acetonitrile/Gradient:52-82(B %)/Flowrate: 25 mL/min/Run time: 10 min) to yield a white solid of N-(3-(2-(dimethylamino)ethoxy)-5-(trifluoromethyl)phenyl)-2-(4-(5-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)acetamide (41.16 mg, 0.079 mmol, 50.6% yield). TLC (DCM/MeOH=10:1, Rf=0.4): 1H NMR (400 MHz, CD3OD) δ 7.56-7.47 (m, 2H), 7.46-7.39 (m, 1H), 7.38-7.29 (m, 3H), 7.24 (d, J=2.2 Hz, 1H), 6.96 (s, 1H), 4.19-4.09 (m, 4H), 3.80 (s, 2H), 2.81 (t, J=5.3 Hz, 2H), 2.36 (s, 6H), 1.47 (t, J=6.9 Hz, 3H). ES-LCMS m/z 522 (M+H).

Workup

  1. filtrationThen the solution was filtered
  2. concentrationconcentrated
  3. customto give the residue
  4. customThe crude material was purified by preparative HPLC (Instrument: Gilson GX281/Column: Gemini 150*25 mm*5 um/Mobile phase A: Water (0.05% ammonia solution)/Mobile phaseB: Acetonitrile/Gradient:52-82(B %)/Flowrate: 25 mL/min/Run time: 10 min)

Sources & evidence

ORD record
ord-fd425c80a9c14394880415b86d95b87a
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

Loading…