Potassium Iodide → (2R,3S)-2-((S)-7-Cyano-2-isopropoxycarbonylamino-2,3-dihydro-1H-cyclopenta[b]indol-4-ylmethyl)-3-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 449828ノート

反応式

HRID 449828 の反応式
[CH:1]([O:4][C:5](=[O:21])[NH:6][C@@H:7]1[CH2:20][C:10]2[NH:11][C:12]3[CH:13]=[CH:14][C:15]([C:18]#[N:19])=[CH:16][C:17]=3[C:9]=2[CH2:8]1)([CH3:3])[CH3:2].[C:22]([O:26][C:27]([N:29]1[CH2:33][CH2:32][C@H:31]([OH:34])[C@H:30]1[CH2:35]OS(C)(=O)=O)=[O:28])([CH3:25])([CH3:24])[CH3:23].C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[K+]>CN(C)C=O.C(OCC)(=O)C>[C:22]([O:26][C:27]([N:29]1[CH2:33][CH2:32][C@H:31]([OH:34])[C@H:30]1[CH2:35][N:11]1[C:12]2[CH:13]=[CH:14][C:15]([C:18]#[N:19])=[CH:16][C:17]=2[C:9]2[CH2:8][C@H:7]([NH:6][C:5]([O:4][CH:1]([CH3:3])[CH3:2])=[O:21])[CH2:20][C:10]1=2)=[O:28])([CH3:25])([CH3:23])[CH3:24]

参加物

7

反応物 4

HCID 4875Potassium IodideHCID 10796Cesium carbonateHCID 58149374(2R,3S)-3-Hydroxy-2-methanesulfonyloxymethyl-pyrrolidine-1-carboxylic acid tert-butyl esterHCID 66933207(S)-(7-Cyano-1,2,3,4-tetrahydrocyclopenta[b]indol-2-yl)carbamic Acid Isopropyl Ester

生成物 1

HCID 66933249(2R,3S)-2-((S)-7-Cyano-2-isopropoxycarbonylamino-2,3-dihydro-1H-cyclopenta[b]indol-4-ylmethyl)-3-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester収率 62.3%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
60 °C

実験手順

A mixture of ((S)-7-cyano-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl)-carbamic acid isopropyl ester (1.50 g, 5.29 mmol), (2R,3S)-3-hydroxy-2-methanesulfonyloxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (3.13 g, 10.59 mmol), cesium carbonate (3.45 g, 10.59 mmol), and potassium iodide (88 mg, 529 μmol) in dimethylformamide (50 mL) is heated in a 60° C. oil bath for two days. After cooling to ambient temperature, the reaction is diluted with ethyl acetate (120 mL) and washed with water (3×100 mL) and brine. The organic portion is dried over sodium sulfate, filtered, and concentrated to dryness. The resulting residue is purified by medium pressure liquid chromatography, eluting with ethyl acetate:chloroform (2:8). Fractions containing pure product are combined and concentrated to afford 1.59 g (62%) of the title compound. LC-ES/MS m/z 505.2 [M+Na]+, TR=3.97 min.

後処理

  1. temperatureAfter cooling to ambient temperature
  2. washwashed with water (3×100 mL) and brine
  3. dry with materialThe organic portion is dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. customThe resulting residue is purified by medium pressure liquid chromatography
  7. washeluting with ethyl acetate:chloroform (2:8)
  8. additionFractions containing pure product
  9. concentrationconcentrated

出典と根拠

ORDレコード
ord-c99e88815a2c43548f77441307b295a8
出典データセット
uspto-grants-2013_07
特許番号
US08486943B2

反応ノート

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