1,2-Dichloroethane → 1-[4-(Pyridin-2-yl)-phenyl]-4(S)-hydroxy-2-N-(N-methoxy-carbonyl-(L)-iso-leucyl)amino-5(S)-N-(N-methoxycarbonyl-(L)-valyl)amino-6-phenyl-2-azahexane
Reaction equation
Cl.[N:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][C:11]([CH2:14][N:15]([NH2:39])[CH2:16][C@H:17]([OH:38])[C@@H:18]([NH:26][C:27](=[O:37])[C@H:28]([CH:34]([CH3:36])[CH3:35])[NH:29][C:30]([O:32][CH3:33])=[O:31])[CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[CH:10][CH:9]=1.COC([NH:44][C@H:45]([C:50]([OH:52])=O)[C@H:46]([CH2:48][CH3:49])C)=O.[CH2:53](Cl)[CH2:54]Cl.C1C=CC2N([OH:66])N=NC=2C=1.CN([CH:70]=[O:71])C>>[N:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:9]=[CH:10][C:11]([CH2:14][N:15]([NH:39][C:50](=[O:52])[C@H:45]([C@H:46]([CH2:53][CH3:54])[CH:48]=[C:49]=[O:66])[NH:44][O:71][CH3:70])[CH2:16][C@H:17]([OH:38])[C@@H:18]([NH:26][C:27](=[O:37])[C@H:28]([CH:34]([CH3:36])[CH3:35])[NH:29][C:30]([O:32][CH3:33])=[O:31])[CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[CH:12][CH:13]=1Participants
6
Reactant 5
Product 1
Procedure
Analogously to Example 1, a solution of 1.26 g (2 mmol) of 1-[4-(pyridin-2-yl)-phenyl]-4(S)-hydroxy-2-amino-5(S)-N-(N-methoxycarbonyl-(L)-valyl)amino-6-phenyl-2-azahexane hydrochloride (Example 49b) in 12 ml of DMF is added dropwise to a mixture of 0.6 g (3.2 mmol) of N-methoxycarbonyl-(L)-iso-leucine, 1.14 g (6 mmol) of EDC, 0.54 g (4 mmol) of HOBT and 1.68 ml of TEA in 13 ml of DMF. After working up, the crude product is digested in DIPE and purified by subsequent medium-pressure column chromatography (SiO2 ; hexane/ethyl acetate) to yield the title compound. TLC: Rf =0.32 (ethyl acetate); HPLC20-100 : tRet =11.04. FAB MS (M+H)+ =691.
Workup
- custompurified by subsequent medium-pressure column chromatography (SiO2 ; hexane/ethyl acetate)
Sources & evidence
- ORD record
- ord-8f9f6867c5814ba682ede614d46daeb1
- Source dataset
- uspto-grants-2000_12
- Patent number
- US06166004
Reaction notes
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