Brodimoprim

Brodimoprim

Clinical data
ATC code	J01EA02 ( WHO )
Identifiers
IUPAC name 5-[(4-Bromo-3,5-dimethoxyphenyl)methyl]pyrimidine-2,4-diamine
CAS Number	56518-41-3  Y
PubChem CID	68760
ChemSpider	62004  Y
UNII	V1YC7T6LLI
KEGG	D07238  Y
ChEBI	CHEBI:131726
ChEMBL	ChEMBL31891  Y
CompTox Dashboard (EPA)	DTXSID20205070
ECHA InfoCard	100.054.745
Chemical and physical data
Formula	C13H15BrN4O2
Molar mass	339.193 g·mol−1
3D model (JSmol)	Interactive image
Melting point	225 to 228 °C (437 to 442 °F)
SMILES Brc1c(OC)cc(cc1OC)Cc2cnc(nc2N)N
InChI InChI=1S/C13H15BrN4O2/c1-19-9-4-7(5-10(20-2)11(9)14)3-8-6-17-13(16)18-12(8)15/h4-6H,3H2,1-2H3,(H4,15,16,17,18) Y Key:BFCRRLMMHNLSCP-UHFFFAOYSA-N Y
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Brodimoprim is a structural derivative of trimethoprim. In brodimoprim, the 4-methoxy group of trimethoprim is replaced with a bromine atom.

As trimethoprim, brodimoprim is a selective inhibitor of bacterial dihydrofolate reductase. ^[1]

Synthesis

Thieme ChemDrug Synthesis: Patent: Alternate aldehyde synthesis:

The treatment of Dimethyl 2,6-dimethoxybenzene-1,4-dicarboxylate [16849-68-6] (1) with hydroxylamine in PPA gives the hydroxamide, PC12398304 (2). Further treatment with PPA led to methyl 4-amino-3,5-dimethoxybenzoate [56066-25-2] (3). Sandmeyer reaction led to Methyl 4-bromo-3,5-dimethoxybenzoate [26050-64-6] (4). Saponification of the ester formed 4-Bromo-3,5-dimethoxybenzoic acid [56518-42-4] (5). Halogenation with thionyl chloride gave 4-Bromo-3,5-dimethoxybenzoyl chloride [56518-43-5] (6). Rosenmund reduction gave 4-Bromo-3,5-dimethoxybenzaldehyde [31558-40-4] (7). {Alternatively DIBAL meant that FGI from ester to aldehyde was accomplished in only 1 step}. Knoevenagel condensation with 3-Methoxypropionitrile [110-67-8] (8) afforded [56518-39-9] (9). Finally, condensation with Guanidine [113-00-8] completed the synthesis of Brodimoprim (10).

References

1. Thomson CJ (December 1993). "Trimethoprim and brodimoprim resistance of gram-positive and gram-negative bacteria". Journal of Chemotherapy. 5 (6): 458–64. doi:10.1080/1120009X.1993.11741096. PMID   8195838.
2. Sweetman, AJ; Serradell, MN; Castaer, J.; Blancafort, P.; Brodimoprim. Drugs Fut 1982, 7, 2, 93.
3. Kompis, Ivan; Wick, Alexander (1977). "Synthese von 4-halogensubstituierten Analogen von Trimethoprim". Helvetica Chimica Acta. 60 (8): 3025–3034. doi:10.1002/hlca.19770600854.
4. Max Dr. Nutley N.J. Us Hoffer, Ivan Dr. Oberwil Ch Kompis, DE2452889 (1985 to F. Hoffmann-La Roche & Co Ag, Basel, Ch); CA, 83, 9736lt
5. Barfknecht, C. F., Nichols, D. E. (April 1971). "Potential psychotomimetics. Bromomethoxyamphetamines". Journal of Medicinal Chemistry. 14 (4): 370–372. doi:10.1021/jm00286a026.