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Diisopropylethylamine → 4-[2-({5-[(R)-2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-1-methyl-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-acetyl]-piperazine-1-carboxylic acid butyl ester

HRID 1970642
ノート
印刷プレビュー

反応式

HRID 1970642 の反応式
[CH2:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:36])[CH2:15][NH:16][C:17]([C:19]2[CH:23]=[C:22]([O:24][C@@H:25]([C:27]([OH:29])=O)[CH3:26])[N:21]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[N:20]=2)=[O:18])[CH2:10][CH2:9]1)=[O:7])[CH2:2][CH2:3][CH3:4].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:70]1([NH:74][C:75]([C@@H:77]2[CH2:81][CH2:80][CH2:79][NH:78]2)=[O:76])[CH2:73][CH2:72][CH2:71]1>CN(C=O)C.ClCCl>[CH2:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([C:14](=[O:36])[CH2:15][NH:16][C:17]([C:19]2[CH:23]=[C:22]([O:24][C@H:25]([CH3:26])[C:27]([N:78]3[CH2:79][CH2:80][CH2:81][C@H:77]3[C:75](=[O:76])[NH:74][CH:70]3[CH2:71][CH2:72][CH2:73]3)=[O:29])[N:21]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[N:20]=2)=[O:18])[CH2:12][CH2:13]1)=[O:7])[CH2:2][CH2:3][CH3:4]
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 62415949(2S)-N-cyclobutylpyrrolidine-2-carboxamideHCID 668560214-(2-{[5-((R)-1-Carboxy-ethoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-acetyl)-piperazine-1-carboxylic acid butyl ester

生成物 1

HCID 66856949
4-[2-({5-[(R)-2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-1-methyl-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-acetyl]-piperazine-1-carboxylic acid butyl ester

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

To a solution of 1.00 g 4-(2-{[5-((R)-1-Carboxy-ethoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-acetyl)-piperazine-1-carboxylic acid butyl ester in 40 ml DMF were added 521 μl DIPEA and 758 mg HATU. After 20 minutes 336 mg (S)-Pyrrolidine-2-carboxylic acid cyclobutylamide were added and the reaction mixture stirred for 3 h. After evaporation of the solvent the crude product was dissolved in dichloromethane and extracted with aqueous LiCl (4% w/w), 0.1 M HCl and aqueous NaHCO3. The crude product obtained after evaporation of the solvent was purified by preparative HPLC (C18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA). The fractions containing the product were immediately lyophilized to yield the pure product which was taken up in dichloromethane and washed once with aqueous NaHCO3. The residue obtained after evaporation of the solvent was lyophilized again to give the title compound. Yield: 517 mg MS (ES+): m/e=652.

後処理

  1. customAfter evaporation of the solvent the crude product
  2. dissolutionwas dissolved in dichloromethane
  3. extractionextracted with aqueous LiCl (4% w/w), 0.1 M HCl and aqueous NaHCO3
  4. customThe crude product obtained
  5. customafter evaporation of the solvent
  6. customwas purified by preparative HPLC (
  7. washC18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA)
  8. additionThe fractions containing the product
  9. customto yield the pure product which
  10. washwashed once with aqueous NaHCO3
  11. customThe residue obtained
  12. customafter evaporation of the solvent

出典と根拠

ORDレコード
ord-775902e94c274a80a8e44fbc02bb977d
出典データセット
uspto-grants-2013_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08426420B2

反応ノート

読み込み中…

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