Cesium carbonate → N-(2,5-difluoro-4-((2-isobutyramidopyridin-4-yl)oxy)phenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide

HRID 1050866Notes

Reaction equation

HRID 1050866 reaction equation
Cl[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]([NH2:42])(=[O:41])[CH:38]([CH3:40])[CH3:39].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[F:36][C:11]1[CH:10]=[C:9]([O:8][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:42][C:37](=[O:41])[CH:38]([CH3:40])[CH3:39])[CH:7]=2)[C:14]([F:15])=[CH:13][C:12]=1[NH:16][C:17]([C:19]1[C:20](=[O:35])[N:21]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)[CH:22]=[CH:23][C:24]=1[O:25][CH2:26][CH3:27])=[O:18]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 68424IsobutyramideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86703361N-(4-((2-chloropyridin-4-yl)oxy)-2,5-difluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide

Product 1

HCID 71575821N-(2,5-difluoro-4-((2-isobutyramidopyridin-4-yl)oxy)phenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamideYield 35%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

Using the procedure of Example 4, N-(4-((2-chloropyridin-4-yl)oxy)-2,5-difluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (0.15 g, 0.29 mmol), isobutyramide (0.10 g, 1.16 mmol), Xantphos (0.02 g, 0.032 mmol), and Cs2CO3 (0.14 g, 0.44 mmol), Pd2(dba)3 (0.015 g, 0.015 mmol), and dioxane (5 mL) were combined to obtain N-(2,5-difluoro-4-((2-isobutyramidopyridin-4-yl)oxy)phenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (55 mg, 35% yield). 1H NMR (400 MHz, DMSO-d6): δ 11.23 (s, 1 H), 10.52 (s, 1 H), 8.34-8.33 (m, 1 H), 8.19 (d, J=5.7 Hz, 1 H), 7.92 (d, J=7.8 Hz, 1 H), 7.69 (d, J=2.4 Hz, 1 H), 7.50-7.49 (m, 3 H), 7.36 (t, J=8.7 Hz, 2 H), 6.74 (dd, J=5.7, 2.5 Hz, 1 H), 6.55 (d, J=7.9 Hz, 1 H), 4.28 (q, J=7.0 Hz, 2 H), 2.69 (m, 1 H), 1.34 (t, J=7.0 Hz, 3 H), 1.02 (d, J=6.8 Hz, 6 H); MS (ESI) m/z: 581.2 (M+H).

Sources & evidence

ORD record
ord-3f439041af2e49a99a0a59eddde350cc
Source dataset
uspto-grants-2016_07
Patent number
US09387202B2

Reaction notes

Loading…