tert-butyl ((2S,3R)-1-((2S,4R)-4-hydroxy-2-(((1R,2S)-1-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-1-yl)-3,5-dimethyl-1-oxonon-8-en-2-yl)carbamate → tert-butyl ((2R,6S,7R,13aS,14aR,16aS,Z)-2-hydroxy-7,9-dimethyl-14a-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecin-6-yl)carbamate

HRID 1852120노트

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HRID 1852120 반응식
[OH:1][C@H:2]1[CH2:6][N:5]([C:7](=[O:26])[C@@H:8]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[C@H:9]([CH3:17])[CH2:10][CH:11]([CH3:16])[CH2:12][CH2:13][CH:14]=[CH2:15])[C@H:4]([C:27](=[O:44])[NH:28][C@:29]2([C:34](=[O:43])[NH:35][S:36]([C:39]3([CH3:42])[CH2:41][CH2:40]3)(=[O:38])=[O:37])[CH2:31][C@H:30]2C=C)[CH2:3]1>ClCCCl.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>[OH:1][C@H:2]1[CH2:6][N:5]2[C:7](=[O:26])[C@@H:8]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:23])([CH3:22])[CH3:24])[C@H:9]([CH3:17])[CH2:10][CH:11]([CH3:16])[CH2:12][CH2:13][CH:14]=[CH:15][C@@H:30]3[CH2:31][C@@:29]3([C:34](=[O:43])[NH:35][S:36]([C:39]3([CH3:42])[CH2:40][CH2:41]3)(=[O:37])=[O:38])[NH:28][C:27](=[O:44])[C@@H:4]2[CH2:3]1

참가 물질

4

반응물 1

HCID 86683198tert-butyl ((2S,3R)-1-((2S,4R)-4-hydroxy-2-(((1R,2S)-1-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-1-yl)-3,5-dimethyl-1-oxonon-8-en-2-yl)carbamate

생성물 1

HCID 71004914tert-butyl ((2R,6S,7R,13aS,14aR,16aS,Z)-2-hydroxy-7,9-dimethyl-14a-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecin-6-yl)carbamate수율 70%

시약·촉매·용매 2

HCID 11763533(1,3-Bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene)(dichloro)((2-((propan-2-yl)oxy)phenyl)methylidene)ruthenium촉매2회HCID 111,2-Dichloroethane용매

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온도
80 °C

실험 절차

A solution of tert-butyl ((2S,3R)-1-((2S,4R)-4-hydroxy-2-(((1R,2S)-1-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-1-yl)-3,5-dimethyl-1-oxonon-8-en-2-yl)carbamate (8.4 g, 13.15 mmol) in DCE (1500 ml) was sparged with nitrogen for 30 min. and then (1,3-Bis-(2,4,6-trimethylphenyl)-2-imidazolidinylidene)dichloro(o-isopropoxyphenylmethylene)ruthenium) Hoveyda-Grubbs Catalyst 2nd Generation, 0.413 g, 0.657 mmol) was added. The reaction solution was heated to 80° C. for 2 h. The reaction was concentrated and purified by silica gel chromatography using a gradient of 20-60% Acetone in hexanes to give tert-butyl ((2R,6S,7R,13aS,14aR,16aS,Z)-2-hydroxy-7,9-dimethyl-14a-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecin-6-yl)carbamate (5.6 g, 70% yield) as a brown solid. MS: MS m/z 611.3 (M++1).

후처리

  1. concentrationThe reaction was concentrated
  2. custompurified by silica gel chromatography

출처 및 근거

ORD 기록
ord-ee49bbbf18f34e90aab27c64885cae9a
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08957203B2

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