Water → HCID 86707751, 화합물

HRID 2410095노트

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HRID 2410095 반응식
[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8](Br)[N:9]([CH:21]([CH3:23])[CH3:22])[C:10]=1[CH:11]([C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=1[CH3:20])[OH:12])=[O:5])[CH3:2].O.[CH3:26][O:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1B(O)O.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.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]([C:6]1[N:7]=[C:8]([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=2[O:27][CH3:26])[N:9]([CH:21]([CH3:23])[CH3:22])[C:10]=1[CH:11]([C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=1[CH3:20])[OH:12])=[O:5])[CH3:2]

참가 물질

7

반응물 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27339582-Methoxyphenylboronic acidHCID 86707752HCID 86707752, 화합물2회

생성물 1

HCID 86707751HCID 86707751, 화합물

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

To a solution of 2-bromo-5-[(4-chloro-2-methyl-phenyl)-hydroxy-methyl]-1-isopropyl-1H-imidazole-4-carboxylic acid ethyl ester (intermediate C, 3.5 g, 8.4 mmol) in dioxane (80 ml)/H2O (20 ml) were added 2-methoxy-phenyl boronic acid (2.0 g, 13.2 mmol), K2CO3 (3 g, 21.7 mmol). The mixture was degassed for 5 min and then Pd(PPh3)4 (1.7 g, 1.5 mmol) was added. The mixture was stirred at 100° C. for 2 h to give a complete conversion. Dioxane was removed under reduced pressure. The residual material was dissolved in EtOAc and extracted with brine. The aqueous layer was washed with EtOAc. The combined organic layers were dried (Na2SO4), filtered and concentrated under reduced pressure. The product was fixed on silica gel and purified by flash chromatography (silica gel, solvent: CH2Cl2/EtOAc, 100:0→80:20) to give the title compound as a yellow foam. tR: 1.27 min (LC-MS 2); ESI-MS 433.3 [M+H]+ (LC-MS 2). 1H-NMR (DMSO-d6, 400 MHz) δ ppm 7.56-7.48 (m, 2H), 7.29-7.05 (m, 3H), 7.34-7.29 (m, 1H), 7.10-7.96 (m, 1H), 6.94-6.91 (m, 1H), 6.52 (d, 1H), 4.58-4.52 (m, 1H), 4.24 (q, 2H), 3.73/3.68 (s, 3H), 2.16 (s, 3H), 1.27 (t, 3H), 1.05 (d, 3H), 0.58 (d, 3H).

후처리

  1. customThe mixture was degassed for 5 min
  2. customto give a complete conversion
  3. customDioxane was removed under reduced pressure
  4. dissolutionThe residual material was dissolved in EtOAc
  5. extractionextracted with brine
  6. washThe aqueous layer was washed with EtOAc
  7. dry with materialThe combined organic layers were dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. custompurified by flash chromatography (silica gel, solvent: CH2Cl2/EtOAc, 100:0→80:20)

출처 및 근거

ORD 기록
ord-0172dcfba3674af1ba9f95fd482f04a2
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08815926B2

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