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

HRID 1050870Notes

Reaction equation

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

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of N-(4-((2-chloropyridin-4-yl)oxy)-2,5-difluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (0.250 g, 0.485 mmol, see: Example 1) and K2CO3 (0.250 g, 1.809 mmol) in isopropanol (10 mL) was heated at 120° C. for 40 min with microwave irradiation. The reaction mixture was concentrated to dryness, was stirred in water (10 mL), filtered, washed, and dried in vacuo to provide N-(4-((2-chloropyridin-4-yl)oxy)-2,5-difluorophenyl)-1-(4-fluorophenyl)-4-isopropoxy-2-oxo-1,2-dihydropyridine-3-carboxamide (190 mg, 74.0% yield) as white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.05 (s, 1 H), 8.31 (m, 2 H), 7.87 (d, J=7.8 Hz, 1 H), 7.51-7.48 (m, 3 H), 7.36 (t, J=8.7 Hz, 2 H), 7.17 (d, J=2.3 Hz, 1 H), 7.04 (dd, J=5.8, 2.3 Hz, 1 H), 6.55 (d, J=8.0 Hz, 1 H), 4.85 (m, 1 H), 1.31 (d, J=6.0 Hz, 6 H); MS (ESI) m/z: 530.1(M+H+).

Workup

concentrationThe reaction mixture was concentrated to dryness
filtrationfiltered
washwashed
customdried in vacuo

Sources & evidence

ORD record: ord-f0d67e9d66e04d13b613df2c26b94812
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09387202B2

Reaction notes

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