Cesium carbonate → N-(2,5-difluorophenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetamide

HRID 1050103노트

반응식

HRID 1050103 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH:11][C:12]2[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=2[F:19])=[O:10])=[C:4]([F:20])[CH:3]=1.[CH2:21]([O:23][C:24]1[C:25]([O:39][CH2:40][C:41]2[CH:46]=[CH:45][C:44]([O:47][CH3:48])=[CH:43][CH:42]=2)=[N:26][CH:27]=[C:28](B2OC(C)(C)C(C)(C)O2)[CH:29]=1)[CH3:22].C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O.C(Cl)Cl.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:19][C:13]1[CH:14]=[CH:15][C:16]([F:18])=[CH:17][C:12]=1[NH:11][C:9](=[O:10])[CH2:8][C:5]1[CH:6]=[CH:7][C:2]([C:28]2[CH:27]=[N:26][C:25]([O:39][CH2:40][C:41]3[CH:42]=[CH:43][C:44]([O:47][CH3:48])=[CH:45][CH:46]=3)=[C:24]([O:23][CH2:21][CH3:22])[CH:29]=2)=[CH:3][C:4]=1[F:20]

참가 물질

8

반응물 3

HCID 10796Cesium carbonateHCID 904159652-(4-bromo-2-fluorophenyl)-N-(2,5-difluorophenyl)acetamideHCID 904167753-Ethoxy-2-((4-methoxybenzyl)oxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine

생성물 1

HCID 90416960N-(2,5-difluorophenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetamide수율 46.6%

시약·촉매·용매 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 6344Dichloromethane용매HCID 312751,4-Dioxane용매

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온도
110 °C

실험 절차

To a solution of 2-(4-bromo-2-fluorophenyl)-N-(2,5-difluorophenyl)acetamide (40 mg, 0.116 mmol), 3-ethoxy-2-((4-methoxybenzyl)oxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (44.8 mg, 0.116 mmol) and Cs2CO3 (114 mg, 0.349 mmol) in 1,4-dioxane (3 mL) and H2O (1 mL) was added PdCl2(dppf) (8.51 mg, 0.012 mmol) in one charge. Then the mixture was stirred at 110° C. in a microwave for 30 min. After LCMS analysis showed the starting material had disappeared, the mixture was filtered. The filtrate was concentrated and evaporated to dryness to give crude product which was dissolved in DCM and washed with H2O and brine. Then the crude product was purified by preparative TLC to give N-(2,5-difluorophenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetamide (45.0 mg, 0.054 mmol, 46.1% yield). 1H NMR: (400 MHz, CD3OD) δ 7.96 (d, J=2.0 Hz, 1H), 7.88 (d, J=9.6 Hz, 1H), 7.46 (d, J=2.0 Hz, 1H), 7.36-7.44 (m, 5H), 7.18 (m, 1H), 6.91 (d, J=8.6 Hz, 2H), 6.87 (br. s., 1H), 5.37 (s, 2H), 4.15-4.13 (m, 2H), 3.88 (s, 2H), 3.79 (s, 3H), 1.43 (t, J=7.0 Hz, 3H); ES-LCMS: m/z 403.0 (M−120+H).

후처리

  1. additioncharge
  2. filtrationthe mixture was filtered
  3. concentrationThe filtrate was concentrated
  4. customevaporated to dryness
  5. customto give crude product which
  6. washwashed with H2O and brine
  7. customThen the crude product was purified by preparative TLC

출처 및 근거

ORD 기록
ord-001e3690b7164a9dbe5587e88e6e9e1a
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09382238B2

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