Sodium Bicarbonate → 6-chloro-2-(4-fluoro-1H-indol-2-yl)pyridin-3-ol

HRID 595544노트

반응식

HRID 595544 반응식
C(OC([N:8]1[C:16]2[C:11](=[C:12]([F:17])[CH:13]=[CH:14][CH:15]=2)[CH:10]=[C:9]1B(O)O)=O)(C)(C)C.[Cl:21][C:22]1[N:27]=[C:26](I)[C:25]([OH:29])=[CH:24][CH:23]=1.C([O-])(O)=O.[Na+]>O1CCOCC1.O.CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:21][C:22]1[N:27]=[C:26]([C:9]2[NH:8][C:16]3[C:11]([CH:10]=2)=[C:12]([F:17])[CH:13]=[CH:14][CH:15]=3)[C:25]([OH:29])=[CH:24][CH:23]=1

참가 물질

8

반응물 3

HCID 516892Sodium BicarbonateHCID 234331586-Chloro-2-iodo-3-hydroxypyridineHCID 44118245(1-(tert-Butoxycarbonyl)-4-fluoro-1H-indol-2-yl)boronic acid

생성물 1

HCID 867262926-chloro-2-(4-fluoro-1H-indol-2-yl)pyridin-3-ol수율 76.5%

시약·촉매·용매 4

HCID 178418476HCID 178418476, 화합물촉매HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

실험 절차

A mixture of (1-(tert-butoxycarbonyl)-4-fluoro-1H-indol-2-yl)boronic acid (5 g, 18.0 mmol), 6-chloro-2-iodopyridin-3-ol (3.82 g, 15.0 mol) and NaHCO3 (3.78 g, 45.0 mol) in 1,4-dioxane (76 mL) and water (7 mL) was stirred at room temperature for 15 min. Then Pd(PPh3)2Cl2 (527 mg, 0.75 mmol) was added under nitrogen atmosphere, and the mixture was heated at 100° C. under N2 for 16 hours. The reaction mixture was cooled to room temperature, diluted with EtOAc (50 mL), filtered and concentrated. The residue was diluted with H2O (60 mL) and EtOAc (30 mL), and the layer was separated, the aqueous layer was extracted with EtOAc (3*30 mL). The combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography (PE/EtOAc=20/1˜3/1) to give 6-chloro-2-(4-fluoro-1H-indol-2-yl)pyridin-3-ol (3 g, yield: 76.5%). 1H-NMR (MeOD, 400 MHz) δ 7.36 (s, 1H), 7.23˜7.27 (m, 2H), 7.03˜7.11 (m, 2H), 6.6˜36.68 (m, 1H). MS (M+H)+: 263/265.

후처리

  1. temperaturethe mixture was heated at 100° C. under N2 for 16 hours
  2. temperatureThe reaction mixture was cooled to room temperature
  3. filtrationfiltered
  4. concentrationconcentrated
  5. additionThe residue was diluted with H2O (60 mL) and EtOAc (30 mL)
  6. customthe layer was separated
  7. extractionthe aqueous layer was extracted with EtOAc (3*30 mL)
  8. washThe combined organic layers were washed with brine (50 mL)
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was purified by column chromatography (PE/EtOAc=20/1˜3/1)

출처 및 근거

ORD 기록
ord-5e1cefd3f7484e24aa880bf619b9fda5
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09242998B2

반응 노트

불러오는 중…