1,2-Dichloroethane → 1-(4-(2-(1-Methyl-1-phenyl-ethyl)-2H-tetrazol-5-yl)-phenyl)-4(S)-hydroxy-2-N-(N-methoxycarbonyl-(L)-tert-leucyl)amino)-5(S)-N-(N-methoxycarbonyl-(L)-iso-leucyl)amino-6-phenyl-2-azahexane

HRID 1276996Notes

Reaction equation

HRID 1276996 reaction equation
[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.Cl.[CH3:29][C:30]([N:38]1[N:42]=[N:41][C:40]([C:43]2[CH:48]=[CH:47][C:46]([CH2:49][N:50]([NH2:75])[CH2:51][C@H:52]([OH:74])[C@@H:53]([NH:61][C:62](=[O:73])[C@H:63]([C@H:69]([CH2:71][CH3:72])[CH3:70])[NH:64][C:65]([O:67][CH3:68])=[O:66])[CH2:54][C:55]3[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=3)=[CH:45][CH:44]=2)=[N:39]1)([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH3:31]>CN(C=O)C.C(OCC)(=O)C.C1(C)C=CC=CC=1.C(Cl)Cl>[CH3:29][C:30]([N:38]1[N:42]=[N:41][C:40]([C:43]2[CH:44]=[CH:45][C:46]([CH2:49][N:50]([NH:75][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])[CH2:51][C@H:52]([OH:74])[C@@H:53]([NH:61][C:62](=[O:73])[C@H:63]([C@H:69]([CH2:71][CH3:72])[CH3:70])[NH:64][C:65]([O:67][CH3:68])=[O:66])[CH2:54][C:55]3[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=3)=[CH:47][CH:48]=2)=[N:39]1)([C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)[CH3:31]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 11263950N-(Methoxycarbonyl)-L-tert-leucineHCID 696863381-{4-[2-(1-methyl-1-phenyl-ethyl)-2H-tetrazol-5-yl]-phenyl}-4(S)-hydroxy-2-amino-5(S)-N-(N-methoxycarbonyl-(L)-iso-leucyl)amino-6-phenyl-2-azahexane hydrochloride

Product 1

HCID 4679761-(4-(2-(1-Methyl-1-phenyl-ethyl)-2H-tetrazol-5-yl)-phenyl)-4(S)-hydroxy-2-N-(N-methoxycarbonyl-(L)-tert-leucyl)amino)-5(S)-N-(N-methoxycarbonyl-(L)-iso-leucyl)amino-6-phenyl-2-azahexane

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 69528308Ethyl acetate toluene methylene chlorideSolvent

Procedure

With the exclusion of air, 128 mg (0.67 mmol) of N-methoxycarbonyl-(L)-tert-leucine (Example 2e), 243 mg (1.27 mmol) of EDC and 114 mg (0.84 mmol) of HOBT are dissolved in 2 ml of DMF. After 15 min, 0.35 ml (2.5 mmol) of TEA and 286 mg (0.42 mmol) of 1-{4-[2-(1-methyl-1-phenyl-ethyl)-2H-tetrazol-5-yl]-phenyl}-4(S)-hydroxy-2-amino-5(S)-N-(N-methoxycarbonyl-(L)-iso-leucyl)amino-6-phenyl-2-azahexane hydrochloride in 1.5 ml of DMF are added. After 20 hours, the mixture is worked up as described under Example 25. Chromatography (SiO2 ; ethyl acetate/toluene/methylene chloride 2:1:1) yields the title compound: TLC: Rf =0.22 (methylene chloride/ethyl acetate 1:1); HPLC20-100 : tRet =17.3; FAB MS (M+H)+ =814.

Workup

  1. waitAfter 20 hours

Sources & evidence

ORD record
ord-0c56a18811124d89aa19d88379203931
Source dataset
uspto-grants-2000_12
Patent number
US06166004

Reaction notes

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