What is 4-Chloro-2,6-diaminopyrimidine?

4-Chloro-2,6-diaminopyrimidine(DACP) is a member of pyrimidines and an organohalogen compound.4-Chloro-2,6-diaminopyrimidine is a white crystal-like solid. 4-Chloro-2,6-diaminopyrimidine is the main raw material for the synthesis of Minoxidil, and it is also used as an auxiliary material for the electrolysis industry. Some of the methods reported in the literature for the preparation of DACP have mostly yields. Low cost, high cost, and complicated procedures. According to the description of European Patent EP0295218: add sodium methoxide to alcohol, and after cooling, add guanidine hydrochloride and ethyl cyanoacetate while stirring, then heat and reflux for 2 hours, and remove the solvent by distillation. Water was added, and then the pH was adjusted to 8 with hydrochloric acid. The solution was cooled, filtered, and dried to obtain 2,4-diamino-6-hydroxypyrimidine (DAHP) in a yield of 79.6%.Then add 2,4-diamino-6-hydroxypyrimidine (DAHP) to phosphorus oxychloride, reflux for 5 hours, remove excess phosphorus oxychloride by distillation, add water in a flowing state, and then add potassium carbonate to adjust pH = 8.5-9.0, centrifugation, filtration, drying, then slurried with tetrahydrofuran and filtered, and then treated with acetone to obtain 2,4-diamino-6-chloropyrimidine (DACP) with a yield of 47.3%.

Fig 1. Chemical structure formula and three-dimensional structure of 4-Chloro-2,6-diaminopyrimidine

In the study of the synthesis of medicidine, the synthesis process of 4-Chloro-2,6-diaminopyrimidine is as follows: the sodium methoxide, guanidine nitrate, and ethyl cyanoacetate are heated under reflux for 2 hours, the methanol is recovered, and the pH is adjusted to 8 with acetic acid. Crystallized with a yield of 81.4%. After adding DAHP to phosphorus oxychloride and refluxing for 2 hours, the remaining phosphorus oxychloride was distilled off, and then diluted 5 times with water, and then neutralized with ammonia water to pH = 8.5, and acetic acid. The ethyl acetate was extracted 6 times, and then ethyl acetate was recovered to obtain a DACP yield of 74.8%[1-3].

References

[1] Mulbry W W. Purification and Characterization of an Inducible s-Triazine Hydrolase from Rhodococcus corallinus NRRL B-15444R[J]. 1994, 60(2):613-8.
[2] Henry C. Koppel, Darrell E. O'Brien, Roland K. Robins. Potential Purine Antagonists. XIX. Synthesis of Some 9-Alkyl(aryl)-2-amino-6-substituted Purines and Related V-Triazolo [d]pyrimidines1[J]. Journal of the American Chemical Society, 1959, 81(12):3046-3051.
[3] Sonia Stoica, George E. Magoulas, Antonia I. Antoniou,etc. Synthesis of minoxidil conjugates and their evaluation as HL-60 differentiation agents[J]. Bioorganic & Medicinal Chemistry Letters, 2016, 26(4):1145-1150.
[4] https://pubchem.ncbi.nlm.nih.gov/compound/67432
[5] https://www.chemspider.com/Chemical-Structure.60757.html?rid=a83d6af5-62fe-4008-819d-c14ebd7ea07c