7520-75-4

Upstream product

• 7721-62-2 4,5-dimethoxy-2-methylbenzaldehyde 
• 124-41-4 sodium methylate 
• 107-13-1 acrylonitrile 
• 494-99-5 1,2-dimethoxy-4-methylbenzene 
• 22002-45-5 2-bromo-4-methylanisole 

Downstream Products

• 6981-18-6 ormetoprim 
• 141292-65-1 (E)-2-(4,5-Dimethoxy-2-methyl-benzyl)-3-dimethylamino-acrylonitrile 
• 63940-81-8 (Z)-2-(4,5-Dimethoxy-2-methyl-benzyl)-3-methoxy-acrylonitrile 
• 7520-76-5 2-Cyan-3-<4,5-Dimethoxy-2-methyl-phenyl>-propionaldehyd-dimethylacetal 

Relevant academic research and scientific papers

Ormetoprim synthesis method

The invention provides an ormetoprim synthesis method. The method includes steps: subjecting p-cresol and dimethyl carbonate to phenolic hydroxymethylation to obtain a compound I; subjecting the compound I and potassium bromide to bromination reaction under an acetic anhydride-nitric acid system to obtain a compound II; taking cuprous chloride as a catalyst, and subjecting the compound II and sodium methylate methanol solution to methoxylation reaction to obtain a compound III; subjecting the compound III and a VHA reagent to formylation reaction to obtain a compound IV; subjecting the compound IV to reaction with sodium methylate and acrylonitrile methanol solution to obtain a compound V; after the compound V is subjected to alkali isomerization to obtain a vinyl ether structure, subjecting to addition reaction with methyl alcohol and direct condensation and cyclization with guanidine to finally obtain a compound VI which is a final product namely ormetoprim. Defects in the prior art are overcome, and the provided ormetoprim synthesis method has advantages of technical simplicity, easiness in acquisition of starting materials, high yield and low production cost.

Methods of using diaminopyrimidine P2X3 and P2X2/3 receptor modulators for treatment of respiratory and gastrointestinal diseases

Methods for treating respiratory and gastrointestinal diseases mediated by a P2X3 and/or a P2X2/3 receptor antagonist, the methods comprising administering to a subject in need thereof an effective amount of a compound of formula (I): or a pharmaceutically acceptable salt thereof, wherein D, X, Y, R1, R2, R3, R4, R5, R6, R7 and R8 are as defined herein.

Diaminopyrimidines as P2X3 and P2X2/3 antagonists

Compounds and methods for treating diseases mediated by a P2X3 and/or a P2X2/3 receptor antagonist, the methods comprising administering to a subject in need thereof an effective amount of a compound of formula (I): or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein D, X, Y, R1, R2, R3, R4, R5, R6, R7 and R8 are as defined herein.

Syntheses of Antibacterial 2,4-Diamino-5-benzylpyrimidines. Ormetoprim and Trimethoprim

A general and mild method for the synthesis of 2,4-diamino-5-benzylpyrimidines was achieved by the Friedel-Crafts reaction between 2-(methoxymethylene)-3-methoxypropanenitrile (10) and an activated aromatic substrate followed by treatment with guanidine.The method is illustrated by a synthesis of ormetoprim (2) in 75percent overall yield from 3,4-dimethoxytoluene (12).Efficient syntheses of trimethoprim (1) and 2 were also accomplished via prior base-catalyzed 1,3-prototropic isomerization of cinnamonitriles 19 and 20, respectively, followed by condensation with guanidine. 12 was prepared from 3-bromo-4-methoxytoluene by a Cu(I)-catalyzed displacement of bromine by methoxide and 4,5-dimethoxy-2-methylbenzaldehyde was obtained from 12 in 87percent yield by a pyridine-catalyzed Vilsmeier reaction using DMF-POCl3.