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 449828노트

반응식

HRID 449828 반응식
[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]

참가 물질

7

반응물 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

생성물 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 ester수율 62.3%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

반응 조건

온도
60 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-c99e88815a2c43548f77441307b295a8
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08486943B2

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