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

HRID 267141

反応式

HRID 267141 の反応式
[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

参加物

7

反応物 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、化合物

生成物 1

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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-ecb3d7a7c46c409ea1dcd2678767cde7
出典データセット
uspto-grants-1997_07
特許番号
US05652369

関連ノート

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