Trifluoroacetic acid → 2-(2-methyl-1-phenyl-1H-imidazol-4-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide

HRID 1898632ノート

反応式

HRID 1898632 の反応式
[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:44])[C@H:8]([NH:12][C:13]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[C:21]([C:24]4[N:25]=[C:26]([CH3:35])[N:27]([C:29]5[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=5)[CH:28]=4)[N:22]=3)[N:17](COCC[Si](C)(C)C)[CH:16]=2)=[O:14])[CH:9]2[CH2:11][CH2:10]2)[CH2:4]1)#[N:2].FC(F)(F)C(O)=O>ClCCl>[C:1]([CH:3]1[CH2:4][N:5]([C:7](=[O:44])[C@H:8]([NH:12][C:13]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[C:21]([C:24]4[N:25]=[C:26]([CH3:35])[N:27]([C:29]5[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=5)[CH:28]=4)[N:22]=3)[NH:17][CH:16]=2)=[O:14])[CH:9]2[CH2:10][CH2:11]2)[CH2:6]1)#[N:2]

参加物

4

反応物 2

HCID 6422Trifluoroacetic acidHCID 673862212-(2-methyl-1-phenyl-1H-imidazol-4-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide

生成物 1

HCID 584385672-(2-methyl-1-phenyl-1H-imidazol-4-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide収率 62%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

2-(2-Methyl-1-phenyl-1H-imidazol-4-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide (68 mg, 0.111 mmol) was dissolved in 0.6 mL of dichloromethane and then stirred in an ice bath. Trifluoroacetic acid (0.4 mL) was added slowly and the ice bath was removed. The reaction was stirred for 3 h and then cooled in ice bath. Sodium bicarbonate solution was added and the mixture was extracted three times with ethyl acetate. The combined organic layers were washed with brine and dried over sodium sulfate. After evaporation, the residue was dissolved in 4 mL of absolute ethanol, sodium acetate (183 mg) was added and the mixture was stirred for 20 h at 60° C. The reaction was cooled, and water and ethyl acetate were added. The layers were separated and the aqueous layer was extracted twice more with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and evaporated. The residue was purified by silica gel chromatography (methanol/dichloromethane) to give 33 mg (62%) of 2-(2-methyl-1-phenyl-1H-imidazol-4-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide. MS: (M+H)+=481; mp=175-179° C.

後処理

  1. customthe ice bath was removed
  2. stirringThe reaction was stirred for 3 h
  3. temperaturecooled in ice bath
  4. additionSodium bicarbonate solution was added
  5. extractionthe mixture was extracted three times with ethyl acetate
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over sodium sulfate
  8. customAfter evaporation
  9. dissolutionthe residue was dissolved in 4 mL of absolute ethanol
  10. additionsodium acetate (183 mg) was added
  11. stirringthe mixture was stirred for 20 h at 60° C
  12. temperatureThe reaction was cooled
  13. additionwater and ethyl acetate were added
  14. customThe layers were separated
  15. extractionthe aqueous layer was extracted twice more with ethyl acetate
  16. washThe combined organic layers were washed with brine
  17. dry with materialdried over sodium sulfate
  18. customevaporated
  19. customThe residue was purified by silica gel chromatography (methanol/dichloromethane)

出典と根拠

ORDレコード
ord-68c7701765474662b4447592ed7dfab3
出典データセット
uspto-grants-2013_08
特許番号
US08518945B2

反応ノート

読み込み中…