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

HRID 1050169Notes

Reaction equation

HRID 1050169 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26][C:27]([NH:29][C:30]3[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[C:32]([O:40][CH2:41][CH2:42][N:43]4[CH2:48][CH2:47][O:46][CH2:45][CH2:44]4)[CH:31]=3)=[O:28])=[C:22]([F:49])[CH:21]=2)[CH:7]=[N:8][C:9]=1[O:10]CC1C=CC(OC)=CC=1)[CH3:2]>C(O)(C(F)(F)F)=O>[CH2:1]([O:3][C:4]1[C:9](=[O:10])[NH:8][CH:7]=[C:6]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26][C:27]([NH:29][C:30]3[CH:35]=[C:34]([C:36]([F:38])([F:39])[F:37])[CH:33]=[C:32]([O:40][CH2:41][CH2:42][N:43]4[CH2:44][CH2:45][O:46][CH2:47][CH2:48]4)[CH:31]=3)=[O:28])=[C:22]([F:49])[CH:21]=2)[CH:5]=1)[CH3:2]

Participants

3

Reactant 1

HCID 904233572-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)-N-(3-(2-morpholinoethoxy)-5-(trifluoromethyl)phenyl)acetamide

Product 1

HCID 784273022-[4-(5-ethoxy-6-oxo-1H-pyridin-3-yl)-2-fluorophenyl]-N-[3-(2-morpholin-4-ylethoxy)-5-(trifluoromethyl)phenyl]acetamideYield 52.1%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of 2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)-N-(3-(2-morpholinoethoxy)-5-(trifluoromethyl)phenyl)acetamide (80 mg, 0.117 mmol) and TFA (10 mL, 10% in DCM) was stirred at 25° C. for 2 h. The mixture was concentrated. To the residue was added NH3 (6 mol/L in MeOH, 1 mL) and concentrated. The residue was purified by preparative TLC (DCM/MeOH=15:1, Rf=0.4) to give an off white solid of 2-(4-(5-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)-N-(3-(2-morpholinoethoxy)-5-(trifluoromethyl)phenyl)acetamide (35.72 mg, 0.061 mmol, 51.7% yield): 1H NMR (400 MHz, CD3OD): δ 7.59 (s, 1H), 7.46 (s, 1H), 7.43-7.37 (m, 1H), 7.36-7.30 (m, 2H), 7.29 (d, J=2.0 Hz, 1H), 7.21 (d, J=2.0 Hz, 1H), 6.96 (s, 1H), 4.23 (t, J=5.2 Hz, 2H), 4.11 (q, J=6.8 Hz, 2H), 3.79 (s, 2H), 3.78-3.69 (m, 4H), 3.02-3.00 (m, 2H), 2.80-2.79 (m, 4H), 1.45 (t, J=6.8 Hz, 3H). ES-LCMS m/z: 564 (M+H).

Workup

  1. concentrationThe mixture was concentrated
  2. additionTo the residue was added NH3 (6 mol/L in MeOH, 1 mL)
  3. concentrationconcentrated
  4. customThe residue was purified by preparative TLC (DCM/MeOH=15:1, Rf=0.4)

Sources & evidence

ORD record
ord-314c8b74e9c04fc5a19d87f3e95847fc
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

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