A kind of synthetic method of β-amino-alpha-hydroxycyclobutanamide hydrochloride

A technology of hydroxycyclobutylbutanamide and synthetic method, which is applied in the field of synthesis of boceprevir intermediates, can solve the problems of low product purity and yield, unfavorable industrial production, unfavorable continuous production, etc., and achieve improved yield and The effects of purity, reduced need for auxiliary raw materials, and fewer reaction steps
CN103387510BInactive Publication Date: 2015-09-09SUZHOU UUGENE BIOPHARMA
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
SUZHOU UUGENE BIOPHARMA
Publication Date
2015-09-09
Estimated Expiration
Not applicable · inactive patent

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Abstract

The invention relates to a synthesis method of beta-amino-alpha-hydroxycyclohexyl butyl aluminum hydrochloride as a boceprevir intermediate. The synthesis method comprises the following steps of: with Boc-tert-butyl glycinate as a compound as shown in the formula (I) as a starting raw material, subjecting the Boc-tert-butyl glycinate and cyclobutyl halogenated methane as a compound as shown in the formula (II) to reaction to generate a compound as shown in the formula (III), reducing the compound to generate a compound as shown in the formula (IV), adding a cyanide and inorganic acid to generate a compound as shown in the formula (V), subjecting the compound and acid to reaction to generate a compound as shown in the formula (VI), adding a hydroxyl protective agent and a catalyst to react to generate a compound as shown in the formula (VII), oxidizing the compound to generate a compound as shown in the formula (VIII), and finally, adding acid to react to generate the beta-amino-alpha-hydroxycyclohexyl butyl aluminum hydrochloride (IX). The synthesis method is few in synthesis step, short in time, less in required auxiliary reagent, low in cost, simple and feasible in after-treatment, simple in equipment and higher in purity and yield.
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Description

technical field

[0001] The invention relates to a method for synthesizing a boceprevir intermediate, in particular to a method for synthesizing a boceprevir intermediate β-amino-alpha-hydroxycyclobutylbutanamide hydrochloride, which belongs to the technical field of drug synthesis. Background technique

[0002] In 2011, Merck successfully developed a hepatitis C virus (HCV) NS3 / 4A protease inhibitor Boceprevir (Boceprevir), its chemical name is: (1R, 2S, 5S)-N-(4-amino- 1-cyclobutyl-3,4-dioxobutan-2-yl)-3-[(2S)-2-(tert-butylcarbamoylamido)-3,3-dimethylbutyryl] -6,6-Dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide, CAS registration number: 394730-60-0, the structural formula is:

[0003]

[0004] It is a small molecule inhibitor with high NS3 inhibitory activity discovered during the systematic truncation and modification of amino acid residues on the ketoamide undecapeptide. It can capture the serine in the active site of NS3 and the carbonyl group on its ketoamide Carb...

Claims

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