Methyl bromoacetate → HCID 12012099, compound

HRID 841133Notes

Reaction equation

HRID 841133 reaction equation
[CH3:1][C@H:2]([NH2:9])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Br[CH2:11][C:12]([O:14][CH3:15])=[O:13]>C(#N)C>[CH3:15][O:14][C:12](=[O:13])[CH2:11][NH:9][C@H:2]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)[CH3:1]

Participants

4

Reactant 2

HCID 60984Methyl bromoacetateHCID 758181-Phenethylamine, (-)-

Product 1

HCID 12012099HCID 12012099, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Scheme 1 shows a method by which the compounds of the present invention can be prepared, by illustrating the synthesis of Example 1, benzyl N-((1S)-1-(1H-4-imidazolylmethyl)-2-2-[(2-methyl-2-phenylpropyl)amino]-2-oxoethyl[(1S)-1-phenylethyl]amino-2-oxoethyl)carbamate. Reaction of (S)-α-methylbenzylamine with methyl bromoacetate was carried out in acetonitrile in the presence of dilsopropylethylamine as the base to give methyl-2-[(1S)-1-phenylethyl]aminoacetate. Methyl-2-[(1S)-1-phenylethyl]aminoacetate was then coupled to Cbz-His(trityl) in methylene chloride with HATU as coupling agent, and diisopropylethylamine as the base. The resulting product was saponified using lithium hydroxide at 0° C., followed by coupling with β,β-dimethylphenethylamine in methylene chloride, with HBTU as coupling agent, and diisopropylethylamine as the base. The trityl group was removed by treatment with 50% TFA in methylene chloride. The β,β-dimethylphenethylamine was prepared from benzyl cyanide, which was treated with 2 equivalents of sodium hydride in tetrahydrofuran (THF) and 2 equivalents of methyl iodide in THF followed by hydrogenation (H2, Pd/C, ammonia) and treatment with HCl to give the HCl salt.

Workup

  1. customcan be prepared

Sources & evidence

ORD record
ord-eb168e5723cd42ea9c78c1686bd9a359
Source dataset
uspto-grants-2002_04
Patent number
US06369034B1

Reaction notes

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