Triethylamine → (2S)-N-((1S,2S)-3-{(2S,4S)-2-[N-(tert-butyl)carbamoyl]-4-chloropyrrolidinyl}-2-hydroxy-3-oxo-1-benzylpropyl)-3-carbamoyl-2-[(phenylmethoxy)carbonylamino]propanamide

HRID 1780235노트

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HRID 1780235 반응식
Cl.[C:2]([NH:6][C:7](=[O:14])[C@@H:8]1[CH2:12][C@H:11]([Cl:13])[CH2:10][NH:9]1)([CH3:5])([CH3:4])[CH3:3].[CH2:15]([O:22][C:23]([NH:25][C@H:26]([C:31]([NH:33][C@@H:34]([CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[C@H:35]([OH:39])[C:36](O)=[O:37])=[O:32])[CH2:27][C:28](=[O:30])[NH2:29])=[O:24])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.P(C#N)(OCC)(OCC)=O.C(N(CC)CC)C>CN(C)C=O>[CH2:15]([O:22][C:23]([NH:25][C@H:26]([C:31]([NH:33][C@@H:34]([CH2:40][C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1)[C@H:35]([OH:39])[C:36]([N:9]1[CH2:10][C@@H:11]([Cl:13])[CH2:12][C@H:8]1[C:7]([NH:6][C:2]([CH3:5])([CH3:3])[CH3:4])=[O:14])=[O:37])=[O:32])[CH2:27][C:28](=[O:30])[NH2:29])=[O:24])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

참가 물질

6

반응물 4

HCID 8471TriethylamineHCID 76257Diethyl cyanophosphonateHCID 57125825(2S,3S)-3-(N2-benzyloxycarbonyl-L-asparaginyl)amino-2-hydroxy-4-phenylbutyric acidHCID 67722329(4S)-N-t-butyl-4-chloro-L-prolinamide hydrochloride

생성물 1

HCID 473123(2S)-N-((1S,2S)-3-{(2S,4S)-2-[N-(tert-butyl)carbamoyl]-4-chloropyrrolidinyl}-2-hydroxy-3-oxo-1-benzylpropyl)-3-carbamoyl-2-[(phenylmethoxy)carbonylamino]propanamide

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

680 mg (2.23 mmol) of (4S)-1-t-butoxycarbonyl-N-t-butyl-4-chloro-L-prolinamide (prepared as described in Preparation 2) were treated with 10 ml of a 4N solution of hydrogen chloride in dioxane, in order to eliminate the t-butoxycarbonyl group and give (4S)-N-t-butyl-4-chloro-L-prolinamide hydrochloride. The whole of the hydrochloride thus obtained and 880 mg (1.99 mmol) of (2S,3S)-3-(N2 -benzyloxycarbonyl-L-asparaginyl)amino-2-hydroxy-4-phenylbutyric acid (prepared as described in Preparation 1) were dissolved in 5 ml of dimethylformamide, and the solution was cooled with ice. 420 mg (2.58 mmol) of diethyl cyanophosphate, followed by 640 mg (6.40 mmol) of triethylamine, were then added to the ice-cooled mixture, and the mixture was stirred for 3 hours. At the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure, and the residue was mixed with a 10% w/v aqueous solution of citric acid and then extracted with ethyl acetate. The organic extract was washed with a 10% w/v aqueous solution of sodium hydrogencarbonate and with a saturated aqueous solution of sodium chloride, in that order, after which it was dried over anhydrous sodium sulfate. The solvent was then removed by distillation under reduced pressure, and the residue was purified by preparative thin layer chromatography using a 10:1 by volume mixture of methylene chloride and methanol as the developing solvent, to give 850 mg of the title compound as a colorless powder, melting at 107°-109° C.

후처리

  1. temperaturethe solution was cooled with ice
  2. temperaturecooled mixture
  3. concentrationAt the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure
  4. additionthe residue was mixed with a 10% w/v aqueous solution of citric acid
  5. extractionextracted with ethyl acetate
  6. extractionThe organic extract
  7. washwas washed with a 10% w/v aqueous solution of sodium hydrogencarbonate and with a saturated aqueous solution of sodium chloride, in that order
  8. dry with materialafter which it was dried over anhydrous sodium sulfate
  9. customThe solvent was then removed by distillation under reduced pressure
  10. customthe residue was purified by preparative thin layer chromatography
  11. additionby volume mixture of methylene chloride and methanol as the developing solvent

출처 및 근거

ORD 기록
ord-f0b75d9522a04845a90692a068cb670e
출처 데이터셋
uspto-grants-1997_05
특허 번호
US05629406

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