Amino­pyrimidine–carboxyl­(ate) interactions in trimethoprim maleate, an antifolate drug

In the title cocrystal, trimethoprim maleate [2,4-di­amino-5-(3,4,5-tri­methoxy­benzyl)­pyrimidin-1-ium maleate], C₁₄H₁₉­N₄O₃⁺·­C₄H₃O₄⁻, the trimethoprim mol­ecule is protonated at N1. The carboxyl group of the maleate ion makes a specific double hydrogen bond of type N—H⃛O with the 2-amino group and the protonated N1 atom of the trimethoprim cation which is similar to the carboxyl­ate–trimethoprim cation interaction observed in the complex of di­hydro­folate reductase with trimethoprim. The pyrimidine moieties of trimethoprim cations are centrosymmetrically paired through a pair of N—H⃛N hydrogen bonds involving the 4-amino group and the pyridinium N3 atom of a symmetry-related molecule. One of the O atoms at the maleate carboxyl­ate group bridges the 2-­amino and 4-amino groups on either side of the paired trimethoprim cations. The other O atom of the carboxyl­ate group forms an intramolecular O—H⃛O hydrogen bond with the carboxyl group. These characteristic hydrogen bonds result in infinite two-dimensional aggregation of rings into a supramolecular ladder, which is further crosslinked through weak C—H⃛O interactions with methoxy groups of neighbouring trimethoprim mol­ecules to form a layered structure.