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

HRID 595656ノート

反応式

HRID 595656 の反応式
[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

参加物

6

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 178418476HCID 178418476、化合物触媒HCID 218864351,4-Dioxane--water (1/1)溶媒

反応条件

温度
100 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-d73cc226d6fc4924a63b21438d1c78c8
出典データセット
uspto-grants-2016_01
特許番号
US09243002B2

反応ノート

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