1,2-Dichloroethane → 1-{4-[2-(1-methyl-1-phenyl-ethyl)-2H-tetrazol-5-yl]-phenyl}-4(S)-hydroxy-2-(tert-butoxycarbonyl)amino-5(S)-N-(N-methoxycarbonyl-(L)-tert-leucyl)amino-6-phenyl-2-azahexane

HRID 1276992Notes

Reaction equation

HRID 1276992 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.[CH3:28][C:29]([N:37]1[N:41]=[N:40][C:39]([C:42]2[CH:47]=[CH:46][C:45]([CH2:48][N:49]([NH:62][C:63]([O:65][C:66]([CH3:69])([CH3:68])[CH3:67])=[O:64])[CH2:50][C@H:51]([OH:61])[C@@H:52]([NH2:60])[CH2:53][C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)=[CH:44][CH:43]=2)=[N:38]1)([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH3:30]>CN(C=O)C>[CH3:30][C:29]([N:37]1[N:41]=[N:40][C:39]([C:42]2[CH:47]=[CH:46][C:45]([CH2:48][N:49]([NH:62][C:63]([O:65][C:66]([CH3:69])([CH3:68])[CH3:67])=[O:64])[CH2:50][C@H:51]([OH:61])[C@@H:52]([NH:60][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])[CH2:53][C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)=[CH:44][CH:43]=2)=[N:38]1)([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH3:28]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 11263950N-(Methoxycarbonyl)-L-tert-leucineHCID 229404511-{4-[2-(1-Methyl-1-phenyl-ethyl)-2H-tetrazol-5-yl]-phenyl}-4(S)-hydroxy-2-(tert-butoxycarbonyl)amino-5(S)-amino-6-phenyl-2-azahexane

Product 1

HCID 696857601-{4-[2-(1-methyl-1-phenyl-ethyl)-2H-tetrazol-5-yl]-phenyl}-4(S)-hydroxy-2-(tert-butoxycarbonyl)amino-5(S)-N-(N-methoxycarbonyl-(L)-tert-leucyl)amino-6-phenyl-2-azahexane

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

With the exclusion of air, 868 mg (4.59 mmol) of N-methoxycarbonyl-(L)-tert-leucine (Example 2e), 1.64 g (8.58 mmol) of EDC and 773 mg (5.72 mmol) of HOBT are dissolved in 24.5 ml of DMF. After 15 min, 2.39 ml (1 7.2 mmol) of TEA and 1.64 g (2.86 mmol) of 1-{4-[2-(1-methyl-1-phenyl-ethyl)-2H-tetrazol-5-yl]-phenyl}-4(S)-hydroxy-2-(tert-butoxycarbonyl)amino-5(S)-amino-6-phenyl-2-azahexane in 12 ml of DMF are added. After 20 hours, the mixture is concentrated by evaporation, and water and methylene chloride are added to the residue; the aqueous phase is separated off and extracted 2× more with methylene chloride. The organic phases are washed with 10% citric acid solution, sat. NaHCO3 solution, water and brine, dried (Na2SO4) and concentrated by evaporation. [Digestion from DIPE yields the title compound: HPLC20-100 : tRet =18.6; FAB MS (M+H)+ =743.

Workup

  1. waitAfter 20 hours
  2. concentrationthe mixture is concentrated by evaporation, and water and methylene chloride
  3. additionare added to the residue
  4. customthe aqueous phase is separated off
  5. extractionextracted 2× more with methylene chloride
  6. washThe organic phases are washed with 10% citric acid solution, sat. NaHCO3 solution, water and brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-279799cfc69f4d2da9284a22922fd296
Source dataset
uspto-grants-2000_12
Patent number
US06166004

Reaction notes

Loading…