4-[2-fluoro-4-(3-hydroxy-1-propynyl)anilino]-N-(2-hydroxyethoxy)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide → 4-[2-Fluoro-4-(3-hydroxypropyl)anilino]-N-(2-hydroxyethoxy)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide

HRID 917698Notes

Reaction equation

HRID 917698 reaction equation
[F:1][C:2]1[CH:23]=[C:22]([C:24]#[C:25][CH2:26][OH:27])[CH:21]=[CH:20][C:3]=1[NH:4][C:5]1[C:6]([C:13]([NH:15][O:16][CH2:17][CH2:18][OH:19])=[O:14])=[CH:7][N:8]([CH3:12])[C:9](=[O:11])[CH:10]=1>CO.[Pd]>[F:1][C:2]1[CH:23]=[C:22]([CH2:24][CH2:25][CH2:26][OH:27])[CH:21]=[CH:20][C:3]=1[NH:4][C:5]1[C:6]([C:13]([NH:15][O:16][CH2:17][CH2:18][OH:19])=[O:14])=[CH:7][N:8]([CH3:12])[C:9](=[O:11])[CH:10]=1

Participants

4

Reactant 1

HCID 111996954-[2-fluoro-4-(3-hydroxy-1-propynyl)anilino]-N-(2-hydroxyethoxy)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide

Product 1

HCID 113035054-[2-Fluoro-4-(3-hydroxypropyl)anilino]-N-(2-hydroxyethoxy)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

4-[2-Fluoro-4-(3-hydroxy-1-propynyl)anilino]-N-(2-hydroxyethoxy)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide (122 mg, 0.33 mmol) was dissolved in MeOH (20 mL), 5% Pd/C (20 mg) added, then the mixture stirred under an atmosphere of hydrogen (60 psi) for 15 h. at R.T. The Pd/C was removed by filtration through Celite® and all solvent removed under reduced pressure to yield crude yellow oil that was purified by chromatography on silica gel (10% MeOH/CH2Cl2 as eluant). 4-[2-Fluoro-4-(3-hydroxypropyl)anilino]-N-(2-hydroxyethoxy)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide was isolated as a pale yellow foam (63%). 1H NMR [(CD3)2SO, 400 MHz] δ 11.60 (v br s, 1H), 9.29 (br s, 1H), 8.13 (s, 1H), 7.33 (t, J=8.3 Hz, 1H), 7.18 (d, J=11.7 Hz, 1H), 7.07 (d, J=7.9 Hz, 1H), 5.40 (s, 1H), 4.77 (br s, 1H), 4.49 (t, J=5.1 Hz, 1H), 3.91 (t, J=3.9 Hz, 2H), 3.62 (t, J=4.8 Hz, 2H), 3.41 (q, J=5.9 Hz, 2H), 3.36 (s, 3H), 2.62 (t, J=7.6 Hz, 2H), 1.74 (pentet, J=7.0 Hz, 2H). HRMS (EI+) calcd for C18H23N3O5F 380.1622 (M+), found 380.1623.

Workup

  1. customThe Pd/C was removed by filtration through Celite®
  2. customall solvent removed under reduced pressure
  3. customto yield crude yellow oil that
  4. customwas purified by chromatography on silica gel (10% MeOH/CH2Cl2 as eluant)

Sources & evidence

ORD record
ord-32831d8f19d14ff9b4a2b2bc73442c43
Source dataset
uspto-grants-2007_09
Patent number
US07273877B2

Reaction notes

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