(2S,4R)-methyl 4-(allylthio)-4-(biphenyl-4-yl)-1-((S)-2-(tert-butoxycarbonylamino)dec-9-enoyl)pyrrolidine-2-carboxylate → (3S,14R,16S,E)-methyl 14-(biphenyl-4-yl)-3-(tert-butoxycarbonylamino)-2-oxo-13-thia-1-azabicyclo[12.2.1]heptadec-10-ene-16-carboxylate

HRID 1666975노트

반응식

HRID 1666975 반응식
[CH2:1]([S:4][C@:5]1([C:33]2[CH:38]=[CH:37][C:36]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)=[CH:35][CH:34]=2)[CH2:9][N:8]([C:10](=[O:28])[C@@H:11]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]C=C)[C@H:7]([C:29]([O:31][CH3:32])=[O:30])[CH2:6]1)[CH:2]=[CH2:3].SC1N=CC=CC=1C(O)=O>ClCCl.CC1C=C(C)C(N2C(=[Ru](Cl)(Cl)=CC3C=CC=CC=3OC(C)C)N(C3C(C)=CC(C)=CC=3C)CC2)=C(C)C=1>[C:36]1([C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=2)[CH:35]=[CH:34][C:33]([C@@:5]23[CH2:9][N:8]([C@H:7]([C:29]([O:31][CH3:32])=[O:30])[CH2:6]2)[C:10](=[O:28])[C@@H:11]([NH:20][C:21]([O:23][C:24]([CH3:25])([CH3:26])[CH3:27])=[O:22])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH:3]=[CH:2][CH2:1][S:4]3)=[CH:38][CH:37]=1

참가 물질

5

반응물 2

HCID 67443577(2S,4R)-methyl 4-(allylthio)-4-(biphenyl-4-yl)-1-((S)-2-(tert-butoxycarbonylamino)dec-9-enoyl)pyrrolidine-2-carboxylateHCID 178524460HCID 178524460, 화합물

생성물 1

HCID 67443818(3S,14R,16S,E)-methyl 14-(biphenyl-4-yl)-3-(tert-butoxycarbonylamino)-2-oxo-13-thia-1-azabicyclo[12.2.1]heptadec-10-ene-16-carboxylate수율 75.3%

시약·촉매·용매 2

HCID 11763533(1,3-Bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene)(dichloro)((2-((propan-2-yl)oxy)phenyl)methylidene)ruthenium촉매HCID 6344Dichloromethane용매

실험 절차

A solution of (2S,4R)-methyl 4-(allylthio)-4-(biphenyl-4-yl)-1-((S)-2-(tert-butoxycarbonylamino)dec-9-enoyl)pyrrolidine-2-carboxylate (108 mg, 0.174 mmol) in Dichloromethane (50 mL) was purged with nitrogen for 30 min. And then Hoveyda-Grubbs Catalyst 2nd Generation (131 mg, 0.209 mmol) was added. The resulting green solution was heated to reflux for 5 h. The reaction was quenched with 2-Mercaptonicotinic acid (54.0 mg, 0.348 mmol) and washed with sat. Na2CO3, and brine. Dried over MgSO4, filtered, concentrated in vacuo. The brown residue was purified by Biotage column, eluted with gradient 5%˜40% EtOAc-Hexane to afford the desired product (3S,14R,16S,E)-methyl 14-(biphenyl-4-yl)-3-(tert-butoxycarbonylamino)-2-oxo-13-thia-1-azabicyclo[12.2.1]heptadec-10-ene-16-carboxylate (86 mg, 0.131 mmol, 75% yield) as an off-white solid.

후처리

  1. temperatureThe resulting green solution was heated
  2. temperatureto reflux for 5 h
  3. washwashed with sat. Na2CO3, and brine
  4. dry with materialDried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe brown residue was purified by Biotage column
  8. washeluted with gradient 5%˜40% EtOAc-Hexane

출처 및 근거

ORD 기록
ord-17d05f1f8a1d48f0a6e44f4df98bd2d9
출처 데이터셋
uspto-grants-2011_10
특허 번호
US08044087B2

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