475086-75-0

Usage

Uses

Used in Pharmaceutical Industry:
SELEXIPAG interMediate is used as an impurity in the development of Selexipag (S253150), a potential drug for the treatment of various vascular disorders. It plays a crucial role in the synthesis and formulation of Selexipag, contributing to its therapeutic effects on pulmonary arterial hypertension and arteriosclerosis obliterans.

Upstream product

• 41270-66-0 2-chloro-5,6-diphenylpyrazine 
• 42042-71-7 4-hydroxy-N-isopropylbutan-1-amine 
• 928-51-8 4-Chloro-1-butanol 
• 18591-57-6 5,6-diphenyl-2-hydroxypyrazine 
• 243472-70-0 2-bromo-5,6-diphenylpyrazine 
• 447-31-4 Desyl chloride 
• 24242-77-1 α-iodo-α-phenylacetophenone 
• 119-53-9 2-hydroxy-2-phenylacetophenone 
• 1484-50-0 desyl bromide 
• 1689-71-0 2,3-diphenyloxirane 
• 75-26-3 isopropyl bromide 

Downstream Products

• 475084-96-9 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}acetic acid tert-butyl ester 
• 475086-01-2 Selexipag 

Relevant academic research and scientific papers

Synthesis method of selexipag intermediate

The invention relates to the technical field of medicine synthesis, in particular to a synthesis method of a selexipag intermediate. The preparation method comprises the following steps: reacting a compound as shown in a formula III with 2-aminoacetamidine hydrobromide under the action of a catalyst to obtain a compound as shown in a formula IV; reacting the compound as shown in the formula IV with 4-bromo-1-butanol under the action of alkali to obtain a compound as shown in a formula V; and carrying out N-alkylation reaction on the compound as shown in the formula V under the action of alkali to obtain the selexipag intermediate as shown in the formula I: 4-[(5, 6-diphenylpyrazine-2-yl) (isopropyl alcohol group) amino]-1-butanol. The invention creates a novel synthesis method of the selexipag intermediate, and the method has the advantages of cheap and easily available raw materials, simple operation, mild conditions and high yield.

High yield preparation method of selexipag intermediate compound under middle conditions

The invention relates to a high yield preparation method of a selexipag intermediate compound under middle conditions. According to the method, styracitol and halogen acid carry out halogenation reactions, and the reaction product and N-aminoacetyl-N-isopropyl n-butanol carry out condensation, ammoxidation, and ring forming reactions to obtain 2-(N-isopropyl-N-4-hydroxylbutyl)amino-5,6-diphenylpyrazine. The compound can be used to prepare selexipag. The raw materials are cheap and easily available, the operation is simple, convenient and safe, the reaction selectivity is good, the yield and purity are high, and the cost is low.

Preparation method for Selexipag intermediate

The invention provides a method for preparing a Selexipag intermediate 4-((5,6-diphenyl-2-pyrazinyl)(1-methylethyl)amino)-1-butanol. The method includes protecting 4-isopropylamino n-butyl alcohol byusing a hydroxy protecting group reagent, performs addition with 5,6-diphenyl-2-pyrazinyl trifluoromethanesulfonate, and obtains a target compound by removing protecting groups. The preparation methodis high in yield, low in production cost, mild in condition, simple in operation and suitable for industrial production.

Synthetic method of selexipag intermediate

The present invention relates to a synthetic method of a selexipag intermediate. The method comprises the following steps: carrying out a nucleophilic substitution reaction on a compound represented by a formula (I) and isopropylamine in an oxygen-free water-free environment in the presence of a hydrogen withdrawing reagent to obtain a compound represented by a formula (II), wherein the structuralformula of the compound represented by the formula (I) is shown in the description, L represents a halogen atom, and the structural formula of the compound represented by the formula (II) is shown inthe description. According to the synthetic method of the selexipag intermediate provided by the invention, in the oxygen-free water-free environment, the compound shown in the formula (I) and the isopropylamine are used as raw materials, the nucleophilic substitution reaction can be performed in the presence of the hydrogen withdrawing reagent to obtain the compound shown in the formula (II), the reaction conditions are mild, the energy consumption is low, the isopropylamine is cheap and easy to obtain, the production costs can be effectively reduced, and the method is suitable for industrial production.

INHIBITORS OF PLATELET FUNCTION AND METHODS FOR USE OF THE SAME

Disclosed herein are small molecule inhibitors of platelet function, and methods of using the small molecules to treat diseases, such as platelet hemostasis and thrombosis. In particular, disclosed herein are compounds of Formula (I) and pharmaceutically acceptable salts thereof: wherein the substituents are as described.

METHOD FOR PREPARING PROSTACYCLIN RECEPTOR AGONIST

The present invention relates to preparation methods of a prostacyclin receptor agonist of 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsulfonyl)acetamide and its intermediates. These methods are simple and convenient to operate, environment-friendly and suitable for industrial production to obtain the product with good yield and high purity.

CRYSTALLINE FORM VI OF SELEXIPAG

The present disclosure relates to solid state forms of Selexipag, processes for preparation thereof and pharmaceutical compositions thereof.

Preparation method of selexipag intermediate

The invention relates to a preparation method of a selexipag intermediate, and belongs to the field of chemical preparation. The selexipag intermediate is 4-[N-(5,6-diphenylpiperazine-2-yl)-N-isopropyl amide]-1-butanol. The preparation method of the selexipag intermediate comprises the following steps: dissolving 5-chloro-2,3-diphenylpyrazine and 4-(isopropyl amide)-1-butanol in an organic solvent; and reacting under the effects of a palladium catalyst, a complex catalyst and alkali to obtain the selexipag intermediate. The preparation method of the selexipag intermediate is simple and convenient to prepare and gentle in reaction conditions, is environmentally friendly, and is suitable for industrial production.

POLYMORPHIC FORMS AND AMORPHOUS SOLID DISPERSION OF SELEXIPAG

The present disclosure relates to crystalline forms of selexipag and their processes for preparation. The present disclosure also relates to an amorphous solid dispersion of selexipag and its processes for their preparation as well as premix of crystalline selexipag and their process.

PROCESS FOR THE PREPARATION OF SELEXIPAG AND INTERMEDIATES THEREOF

The present invention provides processes for the preparation of Selexipag compound of formula (1). The present invention also provides processes for the preparation of 4-[(5,6-diphenyl-pyrazin-2-yl)-isopropyl -amino]-butan-1-ol (2), and 4-isopropylamino-butan-1-ol of formula (3), which are intermediates for the synthesis of Selexipag (1 ).