7520-76-5Relevant academic research and scientific papers
Syntheses of Antibacterial 2,4-Diamino-5-benzylpyrimidines. Ormetoprim and Trimethoprim
Manchand, Percy S.,Rosen, Perry,Belica, Peter S.,Oliva, Gloria V.,Perrotta, Agostino V.,Wong, Harry S.
, p. 3531 - 3535 (2007/10/02)
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.
2,4-Diamino-pyrimidine derivatives and processes
-
, (2008/06/13)
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.
