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 1276971ノート

反応式

HRID 1276971 の反応式
[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

参加物

8

反応物 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

生成物 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)-

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-a50351108b1a4ee3bf9866a222bdc39a
出典データセット
uspto-grants-2000_12
特許番号
US06166004

反応ノート

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