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

HRID 576228
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HRID 576228 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([Cl:19])[CH:13]=2)=[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]>[Cl:19][C:14]1[CH:13]=[C:12]([NH:11][C:9](=[O:10])[CH2:8][C:5]2[CH:6]=[CH:7][C:2]([C:28]3[CH:27]=[N:26][C:25]([O:39][CH2:40][C:41]4[CH:42]=[CH:43][C:44]([O:47][CH3:48])=[CH:45][CH:46]=4)=[C:24]([O:23][CH2:21][CH3:22])[CH:29]=3)=[CH:3][C:4]=2[F:20])[CH:17]=[CH:16][C:15]=1[Cl:18]
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참가 물질

8

반응물 3

HCID 10796Cesium carbonateHCID 904167753-Ethoxy-2-((4-methoxybenzyl)oxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 904170062-(4-bromo-2-fluorophenyl)-N-(3,4-dichlorophenyl)acetamide

생성물 1

HCID 90415929N-(3,4-dichlorophenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetamide수율 52.8%

시약·촉매·용매 4

HCID 44119782
Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)
촉매
HCID 962Water용매
HCID 6344Dichloromethane용매
HCID 312751,4-Dioxane용매

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온도
130 °C

실험 절차

To a solution of 2-(4-bromo-2-fluorophenyl)-N-(3,4-dichlorophenyl)acetamide (60 mg, 0.159 mmol), 3-ethoxy-2-((4-methoxybenzyl)oxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (61.3 mg, 0.159 mmol) and Cs2CO3 (156 mg, 0.477 mmol) in 1,4-dioxane (3 mL) and H2O (1 mL) was added PdCl2(dppf) (11.64 mg, 0.016 mmol) in one charge. The mixture was stirred at 130° C. in the 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 (DCM/MeOH=40/1) to give pure product N-(3,4-dichlorophenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetamide (60.0 mg, 0.084 mmol, 52.7% yield): 1H NMR: (400 MHz, CD3OD) δ 7.95 (d, J=2.0 Hz, 1H), 7.92 (d, J=1.8 Hz, 1H), 7.45 (s, 3H), 7.43-7.37 (m, 5H), 6.91 (d, J=8.6 Hz, 2H), 5.37 (s, 2H), 4.15 (m, 3H), 3.79 (s, 4H), 1.42 (t, J=7.0 Hz, 3H); ES-LCMS: m/z 435 (M-120).

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 (DCM/MeOH=40/1)

출처 및 근거

ORD 기록
ord-d6d60a4278e84b7aa16075fb901f8030
출처 데이터셋
uspto-grants-2015_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09035063B2

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