Dicyclohexylcarbodiimide → N2 [3(S) [[N (benzyloxycarbonyl)-3-cyano-L-alanyl]amino]-2(R)-hydroxy-4-phenylbutyl]-N1-tert.butyl-L-prolinamide hemihydrate

HRID 267141

반응식

HRID 267141 반응식
[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:16]([OH:18])=[O:17])[CH2:13][C:14]#[N:15])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.OC1C2N=[N:26][NH:25]C=2C=CC=1.C1(N=C=NC2CCCCC2)CCCCC1.N#N.[NH2:46][C@@H:47]([CH2:63][C:64]1[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=1)[C@H:48]([OH:62])[CH2:49][C@@:50]1([C:59]([NH2:61])=[O:60])[CH2:54][CH2:53][CH2:52][N:51]1[C:55]([CH3:58])([CH3:57])[CH3:56]>CN(C)C=O.ClCCl>[N:25]#[N:26].[OH2:8].[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:16]([NH:46][C@@H:47]([CH2:63][C:64]1[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=1)[C@H:48]([OH:62])[CH2:49][C@@:50]1([C:59]([NH2:61])=[O:60])[CH2:54][CH2:53][CH2:52][N:51]1[C:55]([CH3:58])([CH3:56])[CH3:57])=[O:18])[CH2:13][C:14]#[N:15])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1.[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:16]([NH:46][C@@H:47]([CH2:63][C:64]1[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=1)[C@H:48]([OH:62])[CH2:49][C@@:50]1([C:59]([NH2:61])=[O:60])[CH2:54][CH2:53][CH2:52][N:51]1[C:55]([CH3:58])([CH3:56])[CH3:57])=[O:17])[CH2:13][C:14]#[N:15])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

참가 물질

7

반응물 4

HCID 10868DicyclohexylcarbodiimideHCID 12771373(2S)-2-{[(Benzyloxy)carbonyl]amino}-3-cyanopropanoic acidHCID 86746262N2 [3(S)-amino-2(R)-hydroxy-4-phenylbutyl]-N1 tert.butyl-L-prolinamideHCID 178418300HCID 178418300, 화합물

생성물 1

HCID 131717591N2 [3(S) [[N (benzyloxycarbonyl)-3-cyano-L-alanyl]amino]-2(R)-hydroxy-4-phenylbutyl]-N1-tert.butyl-L-prolinamide hemihydrate수율 23.4%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

실험 절차

0.122 g of N-(benzyloxycarbonyl)-3-cyano-L-alanine was dissolved in 2 ml of dry dimethylformamide. The solution was stirred and cooled in an ice/salt bath and treated with 0.066 g of hydroxybenzotriazole and 0.1 g of dicyclohexylcarbodiimide. The mixture was stirred for 5 minutes and then treated with 0.163 g of N2 -[3(S)-amino-2(R)-hydroxy-4-phenylbutyl]-N1 -tert.butyl-L-prolinamide in 2.5 ml of dry dichloromethane. The mixture was allowed to warm to room temperature and was then stirred overnight. The resulting dicyclohexylurea was filtered off and washed with methylene chloride. The combined filtrate and washings were evaporated at 40° C. in a vacuum to give an oil which was partitioned between ethyl acetate and water. The organic phase was washed in sequence with saturated aqueous sodium bicarbonate solution and saturated sodium chloride solution and then dried over sodium sulphate. The solvent was removed by evaporation to give an oil which was chromatographed on silica gel using 14% methanol in dichloromethane for the elution. There were thus obtained 50 mg of product which was recrystallized from diethyl ether/n-hexane to give 0.045 g of N2 -[3(S)-[[N-(benzyloxycarbonyl)-3-cyano-L-alanyl]amino]-2(R)-hydroxy-4-phenylbutyl]-N1 -tert.butyl-L-prolinamide hemihydrate as a solid of melting point 65°-70° C. (softening).

후처리

  1. temperaturecooled in an ice/salt bath
  2. stirringThe mixture was stirred for 5 minutes
  3. stirringwas then stirred overnight
  4. filtrationThe resulting dicyclohexylurea was filtered off
  5. washwashed with methylene chloride
  6. customThe combined filtrate and washings were evaporated at 40° C. in a vacuum
  7. customto give an oil which
  8. customwas partitioned between ethyl acetate and water
  9. washThe organic phase was washed in sequence with saturated aqueous sodium bicarbonate solution and saturated sodium chloride solution
  10. dry with materialdried over sodium sulphate
  11. customThe solvent was removed by evaporation
  12. customto give an oil which
  13. customwas chromatographed on silica gel using 14% methanol in dichloromethane for the elution
  14. customwas recrystallized from diethyl ether/n-hexane

출처 및 근거

ORD 기록
ord-ecb3d7a7c46c409ea1dcd2678767cde7
출처 데이터셋
uspto-grants-1997_07
특허 번호
US05652369

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