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 380217Notes

Reaction equation

HRID 380217 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-phenylethyl)-2H-tetrazol-5-yl]-phenyl}-4(S)-hydroxy-2-amino-5(S)-N-(N-methoxycarbonyl-(L)-tertleucyl)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-7e587085976a4a2089b3d64b1e884e98
Source dataset
uspto-grants-2001_10
Patent number
US06300519B1

Reaction notes

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