Sodium Bicarbonate → 6-chloro-2-(5-fluoro-1H-indol-2-yl)pyridin-3-ol

HRID 595656노트

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HRID 595656 반응식
[Cl:1][C:2]1[N:7]=[C:6](I)[C:5]([OH:9])=[CH:4][CH:3]=1.C(OC([N:17]1[C:25]2[C:20](=[CH:21][C:22]([F:26])=[CH:23][CH:24]=2)[CH:19]=[C:18]1B(O)O)=O)(C)(C)C.C([O-])(O)=O.[Na+]>O1CCOCC1.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:1][C:2]1[N:7]=[C:6]([C:18]2[NH:17][C:25]3[C:20]([CH:19]=2)=[CH:21][C:22]([F:26])=[CH:23][CH:24]=3)[C:5]([OH:9])=[CH:4][CH:3]=1

참가 물질

6

반응물 3

HCID 516892Sodium BicarbonateHCID 27632925-Fluoro-1H-indole-2-boronic acid, N-BOC protectedHCID 234331586-Chloro-2-iodo-3-hydroxypyridine

생성물 1

HCID 903334926-chloro-2-(5-fluoro-1H-indol-2-yl)pyridin-3-ol수율 58.2%

시약·촉매·용매 2

HCID 178418476HCID 178418476, 화합물촉매HCID 218864351,4-Dioxane--water (1/1)용매

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온도
100 °C

실험 절차

To a degassed solution of 6-chloro-2-iodopyridin-3-ol (1.0 g, 3.91 mmol) and (1-(tert-butoxycarbonyl)-5-fluoro-1H-indol-2-yl)boronic acid (prepared using the method described in Example 1, 1.3 g, 4.66 mmol) in 1,4-dioxane-H2O (20 mL, 10:1), Pd(PPh3)2Cl2 (120 mg) and NaHCO3 (1.0 g, 11.90 mmol) were added under N2. The mixture was heated to 100° C. overnight. The reaction mixture was cooled to room temperature, filtered and washed with EtOAc. The filtrate was washed with H2O, brine, dried over Na2SO4. After concentrated, the residue was purified by column chromatography (PE:EA 5:1) to give the product of 6-chloro-2-(5-fluoro-1H-indol-2-yl)pyridin-3-ol (600 mg, yield: 58.2%). 1H-NMR (DMSO-d6, 400 MHz) δ 11.37 (br s, 1H), 11.03 (s, 1H), 7.51 (dd, J=8.8, 4.8 Hz, 1H), 7.41 (d, J=8.4 Hz, 1H), 7.34 (dd, J=10.0, 2.4 Hz, 1H), 7.30 (d, J=1.2 Hz, 1H), 7.26 (d, J=8.4 Hz, 1H), 6.94˜6.99 (m, 1H). MS (M+H)+: 263/265.

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered
  3. washwashed with EtOAc
  4. washThe filtrate was washed with H2O, brine
  5. dry with materialdried over Na2SO4
  6. concentrationAfter concentrated
  7. customthe residue was purified by column chromatography (PE:EA 5:1)

출처 및 근거

ORD 기록
ord-d73cc226d6fc4924a63b21438d1c78c8
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09243002B2

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