Potassium Carbonate → N-(4-((2-acetamidopyridin-4-yl)oxy)-2,5-difluorophenyl)-1-(4-fluorophenyl)-4-isopropoxy-2-oxo-1,2-dihydropyridine-3-carboxamide

HRID 1050869Notes

Reaction equation

HRID 1050869 reaction equation
[C:1]([NH:4][C:5]1[CH:10]=[C:9]([O:11][C:12]2[C:17]([F:18])=[CH:16][C:15]([NH:19][C:20]([C:22]3[C:23](=[O:38])[N:24]([C:31]4[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=4)[CH:25]=[CH:26][C:27]=3[O:28][CH2:29][CH3:30])=[O:21])=[C:14]([F:39])[CH:13]=2)[CH:8]=[CH:7][N:6]=1)(=[O:3])[CH3:2].[C:40]([O-])([O-])=O.[K+].[K+]>C(O)(C)C>[C:1]([NH:4][C:5]1[CH:10]=[C:9]([O:11][C:12]2[C:17]([F:18])=[CH:16][C:15]([NH:19][C:20]([C:22]3[C:23](=[O:38])[N:24]([C:31]4[CH:32]=[CH:33][C:34]([F:37])=[CH:35][CH:36]=4)[CH:25]=[CH:26][C:27]=3[O:28][CH:29]([CH3:40])[CH3:30])=[O:21])=[C:14]([F:39])[CH:13]=2)[CH:8]=[CH:7][N:6]=1)(=[O:3])[CH3:2]

Participants

4

Reactant 2

HCID 11430Potassium CarbonateHCID 71566461N-(4-((2-acetamidopyridin-4-yl)oxy)-2,5-difluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide

Product 1

HCID 71575825N-(4-((2-acetamidopyridin-4-yl)oxy)-2,5-difluorophenyl)-1-(4-fluorophenyl)-4-isopropoxy-2-oxo-1,2-dihydropyridine-3-carboxamideYield 71.9%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A mixture of Example 1 (0.400 g, 0.743 mmol) and K2CO3 (0.400 g, 2.89 mmol) in isopropanol (10 mL) was heated at 120° C. for 1 h with microwave irradiation. The solids were removed by filtration and washed with THF. The filtrate was concentrated to dryness. The residue was stirred in water (15 mL) and the remaining solids were collected and crystallized from MeCN to provide N-(4-((2-acetamidopyridin-4-yl)oxy)-2,5-difluorophenyl)-1-(4-fluorophenyl)-4-isopropoxy-2-oxo-1,2-dihydropyridine-3-carboxamide, (0.295 g, 71.9% yield) as white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.03 (s, 1 H), 10.58 (s, 1 H), 8.29 (dd, J=12.6, 7.2 Hz, 1 H), 8.18 (d, J=5.7 Hz, 1 H), 7.87 (d, J=7.8 Hz, 1 H), 7.67 (s, 1 H), 7.50-7.49 (m, 3 H), 7.35 (t, J=8.7 Hz, 2 H), 6.71 (dd, J=5.7, 2.4 Hz, 1 H), 6.55 (d, J=7.9 Hz, 1 H), 4.85 (m, 1 H), 2.03 (s, 3 H), 1.31 (d, J=6.0 Hz, 6 H); MS (ESI) m/z: 553.1 (M+H+).

Workup

  1. customThe solids were removed by filtration
  2. washwashed with THF
  3. concentrationThe filtrate was concentrated to dryness
  4. customthe remaining solids were collected
  5. customcrystallized from MeCN

Sources & evidence

ORD record
ord-1b0377e60123433d888ec52254590b33
Source dataset
uspto-grants-2016_07
Patent number
US09387202B2

Reaction notes

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