1,2-Dichloroethane → 2,5,6,10,13-Pentaazatetradecanedioic acid, 12-(1,1-dimethylethyl)-8-hydroxy-6-((4-(2-(1-methyl-1-phenylethyl)-2H-tetrazol-5-yl)phenyl)methyl)-3-(1-methylpropyl)-4,11-dioxo-9-(phenylmethyl)-, dimethyl ester,(3S-(3R*(R*),8R*,9R*,12R*))-

HRID 1458470Notes

Reaction equation

HRID 1458470 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@H:6]([C:11]([OH:13])=O)[C@H:7]([CH2:9][CH3:10])[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:69]([CH3:72])([CH3:71])[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>[CH3:31][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@H:7]([CH2:9][CH3:10])[CH3:8])[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:69]([CH3:71])([CH3:70])[CH3:72])[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)[CH3:29]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 28378062L-Isoleucine, N-(methoxycarbonyl)-HCID 696857611-{4-[2-(1-Methyl-1-phenyl-ethyl)-2H-tetrazol-5-yl]-phenyl}4(S)-hydroxy-2-amino-5(S)-N-(N-methoxycarbonyl-(L)-tert-leucyl)amino-6-phenyl-2-azahexane hydrochloride

Product 1

HCID 4679732,5,6,10,13-Pentaazatetradecanedioic acid, 12-(1,1-dimethylethyl)-8-hydroxy-6-((4-(2-(1-methyl-1-phenylethyl)-2H-tetrazol-5-yl)phenyl)methyl)-3-(1-methylpropyl)-4,11-dioxo-9-(phenylmethyl)-, dimethyl ester,(3S-(3R*(R*),8R*,9R*,12R*))-

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

With the exclusion of air, 261 mg (1.38 mmol) of N-methoxycarbonyl-(L)-iso-leucine, 496 mg (2.58 mmol) of EDC and 232 mg (1.72 mmol) of HOBT are dissolved in 7.5 ml of DMF. After 15 min, 0.72 ml (5.17 mmol) of TEA and 585 mg (0.86 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)-tert-leucyl)amino-6-phenyl-2-azahexane hydrochloride (Example 25h) in 3.5 ml of DMF are added. After 20 hours, the mixture is worked up as described under Example 25i. Precipitation with DIPE from a concentrated solution in methylene chloride yields the title compound: HPLC20-100 : tRet= 17.5; FAB MS (M+H)+ =814.

Workup

  1. waitAfter 20 hours
  2. customPrecipitation with DIPE from a concentrated solution in methylene chloride

Sources & evidence

ORD record
ord-e80435d34cf64bec9142d270cfa21333
Source dataset
uspto-grants-1998_12
Patent number
US05849911

Reaction notes

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