Piconol → tert-butyl 4-[1-ethyl-6-(pyridin-2-ylmethoxy)-1H-pyrrolo[2,3-b]pyridin-3-yl]-3-oxopiperazine-1-carboxylate

HRID 1622888ノート

反応式

HRID 1622888 の反応式
[CH2:1]([N:3]1[C:7]2=[N:8][C:9](F)=[CH:10][CH:11]=[C:6]2[C:5]([N:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][C:14]2=[O:26])=[CH:4]1)[CH3:2].[N:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[CH2:33][OH:34].[H-].[Na+]>CS(C)=O>[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([O:34][CH2:33][C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][N:27]=3)=[CH:10][CH:11]=[C:6]2[C:5]([N:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][C:14]2=[O:26])=[CH:4]1)[CH3:2]

参加物

5

反応物 3

HCID 11474PiconolHCID 24758Sodium hydride2 回HCID 67817321tert-butyl 4-(1-ethyl-6-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-oxopiperazine-1-carboxylate

生成物 1

HCID 67818259tert-butyl 4-[1-ethyl-6-(pyridin-2-ylmethoxy)-1H-pyrrolo[2,3-b]pyridin-3-yl]-3-oxopiperazine-1-carboxylate収率 79.5%

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

実験手順

To a stirred solution of tert-butyl 4-(1-ethyl-6-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-oxopiperazine-1-carboxylate (5.00 g, 13.80 mmol) and 2-pyridine methanol (1.60 mL, 16.56 mmol) in dimethyl sulphoxide (50 mL), under a nitrogen atmosphere, is added 60% sodium hydride (0.662 g, 16.56 mmol) portionwise. The reaction is stirred at room temperature for 1 h and then heated at 135° C. overnight. The reaction is cooled to room temperature and further 60% sodium hydride (0.662 g, 16.56 mmol) added, and the reaction stirred overnight at room temperature. The reaction is poured onto brine (ca. 500 mL) and the product extracted with CHCl3 (ca. 2×300 mL). The combined organic extracts are dried over magnesium sulphate, filtered, and concentrated in vacuo to give a brown oil. This is purified by column chromatography on silica, eluting with 0 to 80% EtOAc in DCM, to give the title compound as an orange foam (4.952 g, 10.97 mmol). MS (m/z): 452 (M+1).

後処理

  1. temperatureheated at 135° C. overnight
  2. temperatureThe reaction is cooled to room temperature
  3. stirringthe reaction stirred overnight at room temperature
  4. additionThe reaction is poured onto brine (ca. 500 mL)
  5. extractionthe product extracted with CHCl3 (ca. 2×300 mL)
  6. dry with materialThe combined organic extracts are dried over magnesium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a brown oil
  10. customThis is purified by column chromatography on silica
  11. washeluting with 0 to 80% EtOAc in DCM

出典と根拠

ORDレコード
ord-8cd70ba5ca4544e9a310c09d62742b8f
出典データセット
uspto-grants-2014_07
特許番号
US08778946B2

反応ノート

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