1,2-Dichloroethane → 2,5,6,10,13-Pentaazatetradecanedioic acid, 3-(1,1-dimethylethyl)-8-hydroxy-12-(1-methylethyl)-4,11-dioxo-9-(phenylmethyl)-6-((4-(5-thiazolyl)phenyl)methyl)-, dimethyl ester, (3S,8S,9S,12S)-

HRID 1276971노트

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HRID 1276971 반응식
[CH3:1][O:2][C:3]([NH:5][C@H:6]([C:11]([OH:13])=O)[C:7]([CH3:10])([CH3:9])[CH3:8])=[O:4].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[S:28]1[C:32]([C:33]2[CH:38]=[CH:37][C:36]([CH2:39][N:40]([NH2:64])[CH2:41][C@H:42]([OH:63])[C@@H:43]([NH:51][C:52](=[O:62])[C@H:53]([CH:59]([CH3:61])[CH3:60])[NH:54][C:55]([O:57][CH3:58])=[O:56])[CH2:44][C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)=[CH:35][CH:34]=2)=[CH:31][N:30]=[CH:29]1>CN(C=O)C.C(OCC)(=O)C.O>[S:28]1[C:32]([C:33]2[CH:34]=[CH:35][C:36]([CH2:39][N:40]([NH:64][C:11](=[O:13])[C@H:6]([C:7]([CH3:8])([CH3:9])[CH3:10])[NH:5][C:3]([O:2][CH3:1])=[O:4])[CH2:41][C@H:42]([OH:63])[C@@H:43]([NH:51][C:52](=[O:62])[C@H:53]([CH:59]([CH3:61])[CH3:60])[NH:54][C:55]([O:57][CH3:58])=[O:56])[CH2:44][C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)=[CH:37][CH:38]=2)=[CH:31][N:30]=[CH:29]1

참가 물질

8

반응물 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 107684261-[4-(Thiazol-5-yl)-phenyl]-4(S)-hydroxy-2-amino-5(S)-N-(N-methoxycarbonyl-(L)-valyl)amino-6-phenyl-2-azahexaneHCID 11263950N-(Methoxycarbonyl)-L-tert-leucine

생성물 1

HCID 4679472,5,6,10,13-Pentaazatetradecanedioic acid, 3-(1,1-dimethylethyl)-8-hydroxy-12-(1-methylethyl)-4,11-dioxo-9-(phenylmethyl)-6-((4-(5-thiazolyl)phenyl)methyl)-, dimethyl ester, (3S,8S,9S,12S)-

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

Under argon, 213 mg (1.13 mmol) of N-methoxycarbonyl-(L)-tert-leucine (Example 2e), 431 mg (2.25 mmol) of EDC and 304 mg (2.25 mmol) of HOBT are placed in 18 ml of DMF. After 15 min, 627 μl (4.5 mmol) of TEA and 0.75 mmol of 1-[4-(thiazol-5-yl)-phenyl]-4(S)-hydroxy-2-amino-5(S)-N-(N-methoxycarbonyl-(L)-valyl)amino-6-phenyl-2-azahexane are added. After 2 hours, water and ethyl acetate are added; the aqueous phase is separated off and extracted a further 2× with ethyl acetate. The organic phases are washed 2× with water, sat. NaHCO3 solution, 2× water and brine, dried (Na2SO4) and concentrated by evaporation. Column chromatography (SiO2 ; methylene chloride/THF 5:1) and crystallisation from ether yield the title compound: m.p: 200-201° C.; HPLC20-100 : tRet =14.0; FAB MS (M+H)+ =697.

후처리

  1. waitAfter 2 hours
  2. customthe aqueous phase is separated off
  3. extractionextracted a further 2× with ethyl acetate
  4. washThe organic phases are washed 2× with water, sat. NaHCO3 solution, 2× water and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated by evaporation
  7. customColumn chromatography (SiO2 ; methylene chloride/THF 5:1) and crystallisation from ether

출처 및 근거

ORD 기록
ord-a50351108b1a4ee3bf9866a222bdc39a
출처 데이터셋
uspto-grants-2000_12
특허 번호
US06166004

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