1239908-20-3

Usage

Uses

Used in Pharmaceutical Industry:
Ixazomib citrate (USAN) is used as an anticancer agent for the treatment of multiple myeloma. It functions by inhibiting the proteasome, a cellular protein that degrades unneeded or damaged proteins, thus disrupting the cancer cell's ability to survive and proliferate.
Used in Combination Therapy:
Ixazomib citrate (USAN) is used as a component in combination therapy for multiple myeloma. This approach combines the use of ixazomib with other anticancer drugs to enhance the overall treatment efficacy and potentially improve patient outcomes by targeting different aspects of the cancer cell's biology.

Upstream product

• 1201903-03-8 Ν,Ν',Ν''-[boroxin-2,4,6-triyltris[[(1R)-3-methylbutane-1,1-diyl]imino(2-oxoethane-2,1-diyl)]]tris(2,5-dichlorobenzamide) 
• 77-92-9 citric acid 
• 1201903-02-7 2,5-dichloro-N-[2-({(1R)-3-methyl-1-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexa-hydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]butyl}amino)-2-oxoethyl]benzamide 
• 1310383-72-2 (aR,3aS,4S,6S,7aR)-hexahydro-3a,8,8-trimethyl-α-(2-methylpropyl)-4,6-methano-1,3,2-benzodioxaborole-2-methanamine 2,2,2-trifluoroacetate 
• 667403-46-5 2-[(2,5-dichlorobenzoyl)amino]acetic acid 
• 7732-18-5 water 
• 5949-29-1 citric acid monohydrate 
• 50-79-3 2,5-dichlorobenzoic acid 

Relevant academic research and scientific papers

PROCESS FOR THE PREPARATION OF IXAZOMIB CITRATE

The present disclosure provides a process for the preparation of ixazomib citrate. An efficient, industrially feasible process for the preparation of ixazomib citrate of Formula I, optionally which the process can occur in a single pot.

A PROCESS FOR THE PREPARATION OF IXAZOMIB CITRATE

The present invention relates to a process for the preparation of compound of formula (I), wherein, R1 and R2 are each independently hydroxy, alkoxy, aryloxy, or aralkoxy; or R1 and R2 together form a moiety derived from an alpha-hydroxy carboxylic acid compound or a beta-hydroxy carboxylic acid compound, wherein the atom attached to boron in each case is an oxygen atom; or R1 and R2 together form the boronate esters of boronic acid.

Process for preparing ixazomib citrate and intermediates therefor

A process for making ixazomib citrate of formula VI comprising reacting a compound of formula V with citric acid to form ixazomib citrate of formula VI: wherein R is hydrogen or an amide protecting group.

NOVEL CRYSTALLINE FORMS OF IXAZOMIB CITRATE AND ITS PROCESS FOR PREPARATION THEREOF

The present invention related to novel crystalline forms of Ixazomib citrate of formula-I and its process for preparation thereof. The chemical structure of said compound represented by the following formula-I. This invention also provides a process for the preparation of Ixazomib citrate of formula-I and also its solid dispersions.

Synthesizing method of boric acid citric acid ester compounds including ixazomib

The invention relates to a method for synthesizing ixazomib. The method includes the steps of firstly, using 2,5-dichlorobenzoyl chloride or 2,5-dichlorobenzoic acid as the initial raw material, subjecting the 2,5-dichlorobenzoyl chloride or 2,5-dichlorobenzoic acid and glycine ester to condensation reaction to prepare N-(2,5-dichlorobenzoyl) glycine ester, and performing de-protection reaction toobtain N-(2,5-dichlorobenzoyl) glycine; secondly, subjecting the N-(2,5-dichlorobenzoyl) glycine obtained in the first step and (R)-leucine boric acid pinacol ester to condensation reaction to prepare (R)-[N-(2,5-dichlorobenzoyl) glycyl] leucine boric acid pinacol ester; thirdly, allowing the(R)-[N-(2,5-dichlorobenzoyl) glycyl] leucine boric acid pinacol ester obtained in the second step to haveone-step reaction with citric acid to generate the ixazomib. The invention further relates to a method for synthesizing boric acid citric acid ester compounds, and the method includes allowing boric acid pinacol ester to have one-step reaction with citric acid to generate the boric acid citric acid ester compounds. By the methods, the boric acid citric acid ester compounds including the ixazomib can be conveniently synthesized.

Synthetic method of proteasome inhibitor MLN9708

The invention provides a synthetic method of a proteasome inhibitor MLN9708. The method comprises: taking 2,5-dichloro benzoic acid as an initial raw material, and performing condensation and saponification to prepare N-(2,5-dichlorobenzoyl) glycine; joining N-(2,5-dichlorobenzoyl) glycine to L-leucine boronic acid pinacol ester hydrochloride; purifying the obtained product through forming a complex with diethanolamine and performing hydrolysis for deprotection to obtain corresponding free boric acid; and reacting the obtained product with citric acid to obtain MLN9708. The method is cheap and available in raw materials, simple and convenient to operate, mild in reaction conditions and easy for industrial production.

Preparation method of boron-containing compound

The invention discloses a preparation method of boron-containing compound MLN9708. The preparation method of the MLN9708 includes use of a raw material IV convenient and easy to obtain for synthesis of an intermediate II capable of purification by recrystallization and then use of citric acid for boric acid ester exchange reaction to obtain the boron-containing compound MLN9708. The synthetic process route has no special requirement on production equipment, the reaction condition is mild, all the raw materials are commercially available products, and the process route is very suitable for industrial production.

High-efficiency preparation method for high-purity boron-containing compound

The invention discloses a simple high-efficiency preparation method for a high-purity boron-containing compound MLN9708. According to the preparation method for MLN9708, a simple and easily available raw material (II) and citric acid are subjected to a borate exchange reaction, so the boron-containing compound MLN9708 is prepared in one step. The preparation method is short in route, mild in reaction conditions, simple to operate, high in product yield and purity and suitable for industrial production.

SOLID STATE FORMS OF IXAZOMIB CITRATE

The present disclosure encompasses solid state forms of Ixazomib Citrate and pharmaceutical compositions thereof. Also disclosed are processes for preparation of Ixazomib Citrate.

POLYMORPHS OF IXAZOMIB CITRATE AND PROCESSES FOR THE PREPARATION THEREOF

The present disclosure provides amorphous ixazomib citrate and processes for the preparation thereof. Crystalline form Ml, form M2, form M3, and form M4 of ixazomib citrate are also disclosed. The present disclosure also encompasses processes for the preparation of those crystalline forms.