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

HRID 380208Notes

Reaction equation

HRID 380208 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.[S:28]1[CH:32]=[CH:31][N:30]=[C:29]1[C:33]1[CH:38]=[CH:37][C:36]([CH2:39][N:40]([NH:53][C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[CH2:41][C@H:42]([OH:52])[C@@H:43]([NH2:51])[CH2:44][C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)=[CH:35][CH:34]=1>CN(C=O)C>[S:28]1[CH:32]=[CH:31][N:30]=[C:29]1[C:33]1[CH:38]=[CH:37][C:36]([CH2:39][N:40]([NH:53][C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[CH2:41][C@H:42]([OH:52])[C@@H:43]([NH:51][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])[CH2:44][C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)=[CH:35][CH:34]=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 28378062L-Isoleucine, N-(methoxycarbonyl)-

Product 1

HCID 665781501-[4-(Thiazol-2-yl)-phenyl]-4(S)-hydroxy-2-(tert-butoxycarbonyl)amino-5(S)-N-(N-methoxycarbonyl-(L)-iso-leucyl)amino-6-phenyl-2-azahexane

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Under a nitrogen atmosphere, 938 mg (4.96 mmol) of N-methoxycarbonyl-(L)-iso-leucine, 1.78 g (9.3 mmol) of EDC and 838 mg (6.2 mmol) of HOBT are dissolved in 13.7 ml of DMF. After 30 min, 2.6 ml (18.6 mmol) of TEA are added and then a solution of 1.45 g (3.1 mmol) of 1-[4-(thiazol-2-yl)-phenyl]-4(S)-hydroxy-2-(tert-butoxycarbonyl)amino-5(S)-amino-6-phenyl-2-azahexane (Example 17b) in 28 ml of DMF is added dropwise thereto. After 3 hours the reaction mixture is concentrated by evaporation; the residue is taken up in ethyl acetate and a small amount of THF and washed with water, sat. NaHCO3 solution, water and brine. The aqueous phases are extracted with ethyl acetate; the combined organic phases are dried over Na2SO4 and concentrated by evaporation. Column chromatography (SiO2; methylene chloride/THF 5:1) and stirring from ethyl acetate/DIPE yield the title compound: HPLC20-100: tRet=16.3; FAB MS (M+H)+=640.

Workup

  1. concentrationAfter 3 hours the reaction mixture is concentrated by evaporation
  2. washa small amount of THF and washed with water, sat. NaHCO3 solution, water and brine
  3. extractionThe aqueous phases are extracted with ethyl acetate
  4. dry with materialthe combined organic phases are dried over Na2SO4
  5. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-eeff1fe01a4a45dfbe8116e751a6deb1
Source dataset
uspto-grants-2001_10
Patent number
US06300519B1

Reaction notes

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