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 1050866노트

반응식

HRID 1050866 반응식
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]

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

실험 절차

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).

출처 및 근거

ORD 기록
ord-3f439041af2e49a99a0a59eddde350cc
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09387202B2

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