Diisopropylethylamine → 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

HRID 1852119

반응식

HRID 1852119 반응식
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:25]([O:29][C:30]([NH:32][C@@H:33]([C@H:45]([CH3:53])[CH2:46][CH:47]([CH3:52])[CH2:48][CH2:49][CH:50]=[CH2:51])[C:34]([N:36]1[CH2:40][C@H:39]([OH:41])[CH2:38][C@H:37]1[C:42]([OH:44])=O)=[O:35])=[O:31])([CH3:28])([CH3:27])[CH3:26].Cl.[NH2:55][C@:56]1([C:61]([NH:63][S:64]([C:67]2([CH3:70])[CH2:69][CH2:68]2)(=[O:66])=[O:65])=[O:62])[CH2:58][C@H:57]1[CH:59]=[CH2:60].CCN(C(C)C)C(C)C>C(Cl)Cl>[OH:41][C@H:39]1[CH2:40][N:36]([C:34](=[O:35])[C@@H:33]([NH:32][C:30](=[O:31])[O:29][C:25]([CH3:27])([CH3:28])[CH3:26])[C@H:45]([CH3:53])[CH2:46][CH:47]([CH3:52])[CH2:48][CH2:49][CH:50]=[CH2:51])[C@H:37]([C:42](=[O:44])[NH:55][C@:56]2([C:61](=[O:62])[NH:63][S:64]([C:67]3([CH3:70])[CH2:69][CH2:68]3)(=[O:66])=[O:65])[CH2:58][C@H:57]2[CH:59]=[CH2:60])[CH2:38]1

참가 물질

6

반응물 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 66650595853269-58-6HCID 86683196(2S,4R)-1-((2S,3R)-2-((tert-butoxycarbonyl)amino)-3,5-dimethylnon-8-enoyl)-4-hydroxypyrrolidine-2-carboxylic acid

생성물 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)carbamate수율 74%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

HATU (7.60 g, 20.00 mmol) was added to a solution of (2S,4R)-1-((2S,3R)-2-((tert-butoxycarbonyl)amino)-3,5-dimethylnon-8-enoyl)-4-hydroxypyrrolidine-2-carboxylic acid (7.86 g, 19.05 mmol), (1R,2S)-1-amino-N-((1-methylcyclopropyl)sulfonyl)-2-vinylcyclopropanecarboxamide HCl (5.62 g, 20 mmol), and Hunig's Base (13.31 mL, 76 mmol) in DCM (110 mL). The reaction mixture was stirred at rt for 16 h. The reaction was washed with 1N HCl (3×), and then brine. The organic layer was collected, dried over sodium sulfate, and concentrated under vacuum. The crude material was purified by silica gel chromatography using a gradient of 20-60% Acetone in hexanes. The product fractions were collected and the solvent removed under vacuum to give 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 (9 g, 74.0% yield) as a light orange foam. MS: MS m/z 639.3 (M++1).

후처리

  1. washThe reaction was washed with 1N HCl (3×)
  2. customThe organic layer was collected
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customThe crude material was purified by silica gel chromatography
  6. customThe product fractions were collected
  7. customthe solvent removed under vacuum

출처 및 근거

ORD 기록
ord-b273442dcf634d2e9907b069966417f5
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08957203B2

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