Water → [2'-[(Cyclopropanecarbonyl-ethyl-amino)-methyl]-4'-(6-ethoxy-pyridin-3-yl)-6-methoxy-biphenyl-3-yl]-acetic acid ethyl ester

HRID 1625675노트

반응식

HRID 1625675 반응식
[CH2:1]([O:3][C:4](=[O:30])[CH2:5][C:6]1[CH:7]=[C:8]([C:14]2[CH:19]=[CH:18][C:17](Br)=[CH:16][C:15]=2[CH2:21][N:22]([C:25]([CH:27]2[CH2:29][CH2:28]2)=[O:26])[CH2:23][CH3:24])[C:9]([O:12][CH3:13])=[CH:10][CH:11]=1)[CH3:2].O.[CH2:32]([O:34][C:35]1[CH:40]=[CH:39][C:38](B2OC(C)(C)C(C)(C)O2)=[CH:37][N:36]=1)[CH3:33].C(=O)([O-])[O-].[K+].[K+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([O:3][C:4](=[O:30])[CH2:5][C:6]1[CH:7]=[C:8]([C:14]2[CH:19]=[CH:18][C:17]([C:38]3[CH:37]=[N:36][C:35]([O:34][CH2:32][CH3:33])=[CH:40][CH:39]=3)=[CH:16][C:15]=2[CH2:21][N:22]([C:25]([CH:27]2[CH2:29][CH2:28]2)=[O:26])[CH2:23][CH3:24])[C:9]([O:12][CH3:13])=[CH:10][CH:11]=1)[CH3:2]

참가 물질

7

반응물 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 242087962-Ethoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 58149020{4'-Bromo-2'-[(cyclopropanecarbonyl-ethyl-amino)-methyl]-6-methoxy-biphenyl-3-yl}-acetic acid ethyl ester

생성물 1

HCID 58149167[2'-[(Cyclopropanecarbonyl-ethyl-amino)-methyl]-4'-(6-ethoxy-pyridin-3-yl)-6-methoxy-biphenyl-3-yl]-acetic acid ethyl ester

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 80711,2-Dimethoxyethane용매

반응 조건

온도
80 °C

실험 절차

{4′-Bromo-2′-[(cyclopropanecarbonyl-ethyl-amino)-methyl]-6-methoxy-biphenyl-3-yl}-acetic acid ethyl ester (14.5 g, 30.6 mmol) was dissolved in DME (100 mL) and water (50 mL) along with 2-ethoxy-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridine (9.1 g, 36.5 mmol) and potassium carbonate (10.7 g, 77.4 mmol) under N2 atmosphere. The mixture was purged with N2, and then tetrakis(triphenylphosphine)palladium(0) (0.500 g, 0.43 mmol) was added and the reaction was heated to 80° C. The reaction was monitored by analytical LCMS and when the starting material was consumed, the mixture was cooled to room temperature and diluted with ethyl acetate and water. The aqueous layer was separated and extracted with ethyl acetate, and the combined organic layers were dried over magnesium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography (0-35% ethyl acetate in hexanes) to afford the title compound.

후처리

  1. customThe mixture was purged with N2
  2. customwas consumed
  3. temperaturethe mixture was cooled to room temperature
  4. additiondiluted with ethyl acetate and water
  5. customThe aqueous layer was separated
  6. extractionextracted with ethyl acetate
  7. dry with materialthe combined organic layers were dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by silica gel chromatography (0-35% ethyl acetate in hexanes)

출처 및 근거

ORD 기록
ord-72fd29e100984f129d4e3b28489b861f
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08785393B2

반응 노트

불러오는 중…