1,2-Dichloroethane → 1-[4-(Thiazol-2-yl)-phenyl]-4(S)-hydroxy-2-(tert-butoxycarbonyl)amino-5(S)-N-(N-methoxycarbonyl-(L)-valyl)amino-6-phenyl-2-azahexane

HRID 1276981Notes

Reaction equation

HRID 1276981 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@H:6]([C:10]([OH:12])=O)[CH:7]([CH3:9])[CH3:8])=[O:4].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[S:27]1[CH:31]=[CH:30][N:29]=[C:28]1[C:32]1[CH:37]=[CH:36][C:35]([CH2:38][N:39]([NH:52][C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[CH2:40][C@H:41]([OH:51])[C@@H:42]([NH2:50])[CH2:43][C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)=[CH:34][CH:33]=1>CN(C=O)C>[S:27]1[CH:31]=[CH:30][N:29]=[C:28]1[C:32]1[CH:37]=[CH:36][C:35]([CH2:38][N:39]([NH:52][C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[CH2:40][C@H:41]([OH:51])[C@@H:42]([NH:50][C:10](=[O:12])[C@H:6]([CH:7]([CH3:8])[CH3:9])[NH:5][C:3]([O:2][CH3:1])=[O:4])[CH2:43][C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)=[CH:34][CH:33]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 105044891-[4-(Thiazol-2-yl)-phenyl]-4(S)-hydroxy-2-(tert-butoxycarbonyl)amino-5(S)-amino-6-phenyl-2-azahexaneHCID 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acid

Product 1

HCID 106277421-[4-(Thiazol-2-yl)-phenyl]-4(S)-hydroxy-2-(tert-butoxycarbonyl)amino-5(S)-N-(N-methoxycarbonyl-(L)-valyl)amino-6-phenyl-2-azahexane

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Under a nitrogen atmosphere, 1.4 g (8.0 mmol) of N-methoxycarbonyl-(L)-valine, 2.87 g (15 mmol) of EDC and 1.35 g (10 mmol) of HOBT are dissolved in 22 ml of DMF. After 45 min, 4.2 ml (30 mmol) of TEA are added and then a solution of 2.34 g (5.0 mmol) of 1-[4-(thiazol-2-yl)-phenyl]-4(S)-hydroxy-2-(tert-butoxycarbonyl)amino-5(S)-amino-6-phenyl-2-azahexane in 45 ml of DMF is added dropwise. After 1.5 hours, the reaction mixture is concentrated by evaporation; the residue is taken up in methylene chloride and washed with water, sat. NaHCO3 solution, water and brine. The aqueous phases are extracted 2× with methylene chloride; the combined organic phases are dried (Na2SO4) and concentrated by evaporation. Column chromatography (SiO2 ; methylene chloride/ethyl acetate 2:1) and crystallisation from ethel acetate/ether yield the title compound: m.p: 178-179° C.; HPLC20-100 : tRet =15.8.

Workup

  1. waitAfter 1.5 hours
  2. concentrationthe reaction mixture is concentrated by evaporation
  3. washwashed with water, sat. NaHCO3 solution, water and brine
  4. extractionThe aqueous phases are extracted 2× with methylene chloride
  5. dry with materialthe combined organic phases are dried (Na2SO4)
  6. concentrationconcentrated by evaporation
  7. customColumn chromatography (SiO2 ; methylene chloride/ethyl acetate 2:1) and crystallisation from ethel acetate/ether

Sources & evidence

ORD record
ord-d451a6a9b5f149dead943623b932ce03
Source dataset
uspto-grants-2000_12
Patent number
US06166004

Reaction notes

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