Trifluoroacetic acid → (4,4-Difluoro-piperidin-1-yl)-[1-(2-hydroxy-ethyl)-5-(1-isopropyl-piperidin-4-yloxy)-1H-pyrrolo[2,3-b]pyridin-2-yl]-methanone

HRID 1437721ノート

反応式

HRID 1437721 の反応式
C([Si](C)(C)[O:6][CH2:7][CH2:8][N:9]1[C:13]2=[N:14][CH:15]=[C:16]([O:18][CH:19]3[CH2:24][CH2:23][N:22]([CH:25]([CH3:27])[CH3:26])[CH2:21][CH2:20]3)[CH:17]=[C:12]2[CH:11]=[C:10]1[C:28]([N:30]1[CH2:35][CH2:34][C:33]([F:37])([F:36])[CH2:32][CH2:31]1)=[O:29])(C)(C)C.FC(F)(F)C(O)=O>>[F:37][C:33]1([F:36])[CH2:34][CH2:35][N:30]([C:28]([C:10]2[N:9]([CH2:8][CH2:7][OH:6])[C:13]3=[N:14][CH:15]=[C:16]([O:18][CH:19]4[CH2:24][CH2:23][N:22]([CH:25]([CH3:27])[CH3:26])[CH2:21][CH2:20]4)[CH:17]=[C:12]3[CH:11]=2)=[O:29])[CH2:31][CH2:32]1

参加物

3

反応物 2

HCID 6422Trifluoroacetic acidHCID 68423931[1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-5-(1-isopropyl-piperidin-4-yloxy)-1H-pyrrolo[2,3-b]pyridin-2-yl]-(4,4-difluoro-piperidin-1-yl)-methanone

生成物 1

HCID 16727146(4,4-Difluoro-piperidin-1-yl)-[1-(2-hydroxy-ethyl)-5-(1-isopropyl-piperidin-4-yloxy)-1H-pyrrolo[2,3-b]pyridin-2-yl]-methanone収率 66.4%

実験手順

The solution of 55 mg (97 μmol) [1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-5-(1-isopropyl-piperidin-4-yloxy)-1H-pyrrolo[2,3-b]pyridin-2-yl]-(4,4-difluoro-piperidin-1-yl)-methanone was cooled down to 0° C. and 1 ml (1.49 g, 13 mmol) trifluoroacetic acid was added. The cooling bath was removed and stirring was continued for another hour at room temperature. The reaction was neutralized with 1M aqueous sodium hydroxide solution and extracted three times with dichloromethane. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and evaporated. The crude product was purified by flash-chromatography on silica gel with dichloromethane:methanol:ammonia (9:1:0.1 v/v) as eluant to give 29 mg (66%) of the product as a light yellow oil.

後処理

  1. customThe cooling bath was removed
  2. waitwas continued for another hour at room temperature
  3. extractionextracted three times with dichloromethane
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude product was purified by flash-chromatography on silica gel with dichloromethane:methanol:ammonia (9:1:0.1 v/v) as eluant

出典と根拠

ORDレコード
ord-34dfcec97d8d405482f704da35a7892f
出典データセット
uspto-grants-2009_11
特許番号
US07622466B2

反応ノート

読み込み中…