- A process for preparing 5 - substituted benzyl - 2, 4 - diamino pyrimidine and its derivatives (by machine translation)
-
The invention discloses a process for preparing 5 - substituted benzyl - 2, 4 - diamino pyrimidine and derivatives thereof, in particular can be used for preparing omay pullin, b a oxygen animal pen amine pyrimidine, such as palestinian kuikui purin. The invention relates to 5 - hydroxymethyl uracil as raw materials, through the electrophilic substitution reaction, chlorinated, amino and hydrolysis step preparation 5 - substituted benzyl - 2, 4 - diamino pyrimidine and its derivatives. The method can be used for preparing various 5 - substituted benzyl - 2, 4 - diaminopyrimidines of the molecule, thereby avoiding the high-pressure reaction step, the safety is high, and is suitable for industrial production. (by machine translation)
- -
-
-
- 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.
- -
-
-
- Identification and SAR of novel diaminopyrimidines. Part 1: The discovery of RO-4, a dual P2X3/P2X2/3 antagonist for the treatment of pain
-
P2X purinoceptors are ligand-gated ion channels whose endogenous ligand is ATP. Both the P2X3 and P2X2/3 receptor subtypes have been shown to play an important role in the regulation of sensory function and dual P2X3/P2X2/3 antagonists offer significant potential for the treatment of pain. A high-throughput screen of the Roche compound collection resulted in the identification of a novel series of diaminopyrimidines; subsequent optimization resulted in the discovery of RO-4, a potent, selective and drug-like dual P2X3/P2X2/3 antagonist.
- Carter, David S.,Alam, Muzaffar,Cai, Haiying,Dillon, Michael P.,Ford, Anthony P.D.W.,Gever, Joel R.,Jahangir, Alam,Lin, Clara,Moore, Amy G.,Wagner, Paul J.,Zhai, Yansheng
-
scheme or table
p. 1628 - 1631
(2009/11/30)
-
- 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.
- -
-
Page/Page column 83
(2010/11/26)
-
- 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.
- -
-
Page/Page column 89
(2010/02/14)
-
- 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.
- Manchand, Percy S.,Rosen, Perry,Belica, Peter S.,Oliva, Gloria V.,Perrotta, Agostino V.,Wong, Harry S.
-
p. 3531 - 3535
(2007/10/02)
-
- Benzyl cyanoacetals
-
Benzyl cyanoacetals of formula: STR1 wherein R1, R2 and R3 are the same or different and each is a halogen or a hydrogen atom, an alkoxy group, an alkyl group, or a dialkylamino group; R4 is an alkoxycarbonyl group, or an aldehyde group; And R5 is an alkyl group; the alkyl or alkoxy groups each having from 1 to 4 carbon atoms, and their use as intermediates in the preparation of antibacterial 2,4-diamino-5-benzylpyrimidines. They are prepared from a reaction between an orthoester and an α-substituted-β-benzylpropionitrile and then the resulting cyanoacetal is converted to the benzyl-pyrimidine by reaction with guanidine.
- -
-
-
- Process for substituted 5-benzyl-2,4-diamino-pyrimidines
-
A process for preparing a compound of the formula STR1 wherein R1 and R2 are lower alkoxy or taken together are METHYLENEDIOXY; R3 is lower alkyl or hydrogen, which comprises the step of reacting an aromatic compound of the formula STR2 wherein R1, R2 and R3 are as previously described, with a diamino-pyrimidine of the formula STR3 wherein R4 is lower alkoxy, benzyloxy, hydroxy or halogen, in the presence of an inorganic or organic acid selected from the group consisting of ortho-phosphoric acid, poly-phosphoric acid, hydrohalic acids and tri-haloacetic acids, at a temperature in the range of from about 50° C. to about 110° C., is described.
- -
-
-
- Process for preparing substituted 2,4-diaminopyrimidines and isoxazole intermediate
-
A process for the preparation of 2,4-diamino-5-benzylpyrimidines by reacting 4-bromomethylisoxazole with an aromatic compound of the formula STR1 wherein R, R1 and R2 are hydrogen, lower alkoxy and lower alkyl, AND SUBSEQUENTLY TREATING THE REACTION PRODUCT WITH A GUANIDINE SALT, IS DESCRIBED.
- -
-
-
- Process for preparing 2,4-diamino-5-(substituted benzyl)-pyrimidines
-
2,4-Diaminopyrimidines bearing a substituted benzyl group in position-1 are prepared from the correspondingly substituted α-alkoxymethylcinnamonitrile by treatment of the latter with an alkali metal alkoxide in mono-methyl ether of ethylene glycol and subsequently reacting the resulting reaction mixture with guanidine.
- -
-
-
- 2,4-Diamino-pyrimidine derivatives and processes
-
The present invention relates to a new synthesis for the preparation of 5-(substituted benzyl)-2,4-diamino-pyrimidines, including new pyrimidine derivatives. More particularly, a new synthesis of ormetoprin, diaveridine and related compounds, including novel derivatives, is disclosed. The synthesis involves the condensation of a substituted benzene and an acrylonitrile derivative to directly give enol ether intermediates, which upon subsequent reaction by known techniques with guanidine, provides the desired 5-(substituted benzyl)-2,4-diamino-pyrimidines, including novel compounds. The pyrimidine end products are useful as potentiators of sulfonamides and as antibacterial agents.
- -
-
-
- Preparation of β-anilino-α-benzylacrylonitriles
-
Compounds comprising selected N-substituted β-amino-α-benzyl-acrylonitriles and methods of preparing said compounds substantially free from the corresponding bensalacrylonitrile. The compounds are useful as intermediates in the preparation of antibacterial and antimalerial agents.
- -
-
-