Uses
Microwave-assisted synthesis of pyrazolo [3, 4-d] pyrimidines from 2-amino-4, 6-dichloropyrimidine-5-carbaldehyde is under solvent-free conditions. A series of 6-alkynyl-2,4-diaminopyrimidine derivatives bearing various substituents at alkynyl moiety was prepared by the Sonogashira cross-coupling reaction of 2,4-diamino-6-iodopyrimidine using Pd(PPh3)2Cl2 as catalyst.
Synthesis
The general procedure for the synthesis of 2-amino-4,6-dichloropyrimidine from 2-amino-4,6-dihydroxypyrimidine is as follows: in a four-necked flask equipped with a reflux condenser, 510 g of 2-amino-4,6-dihydroxypyrimidine (98% purity, 4 mol) and 1428 g of phosphorus triclosan (99% purity) were added, heated and stirred. 810 g of triethylamine (99% purity) was slowly added dropwise at 40 to 45 °C through a constant pressure dropping funnel. After the dropwise addition, the reaction temperature was raised to 85 to 90 °C and maintained at this temperature for 2 hours. The progress of the reaction was monitored by high performance liquid chromatography (HPLC) and the reaction was considered complete when the amount of 2-amino-4,6-dihydroxypyrimidine was less than 1%. Subsequently, 3000 g of toluene was added to the reaction mixture, cooled to 0-10°C, and 3000 g of ice-water mixture was added for low temperature hydrolysis. The mixture was then warmed to room temperature and left to stratify. The aqueous layer was extracted twice with 400 g of toluene, and the organic phases were combined and washed sequentially with aqueous sodium carbonate and water until neutral. The organic phase was concentrated and 1800 g of toluene was recovered to give 2668 g of highly concentrated toluene solution. The product was analyzed by HPLC, the purity was 96.8%, the content was 22.58% (external standard method), and the yield of crude product was 92%.
References
[1] Patent: CN108395409, 2018, A. Location in patent: Paragraph 0046-0047; 0050
[2] Organic Letters, 2009, vol. 11, # 1, p. 61 - 64
[3] Chemical Communications, 2017, vol. 53, # 18, p. 2689 - 2692
[4] Organic and Biomolecular Chemistry, 2017, vol. 15, # 47, p. 10087 - 10094
[5] Tetrahedron Letters, 2015, vol. 56, # 10, p. 1179 - 1182
