Extended knowledge of 5-Amino-4-methylpyrimidine

Synthetic Route of 3438-61-7, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 3438-61-7, name is 5-Amino-4-methylpyrimidine, molecular formula is C5H7N3, The compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

225.0 g (2.06 mol) of 4-methyl-5-aminopyrimidine was dissolved in 10.0 L of anhydrous THF in a dry flask under nitrogen blanket. The solution was cooled to -200C. 2.0 L (1.39 kg, 5.00 mol) of 2.5 M «-BuLi in hexane was added in 20 minutes while the temperature was kept below -50C. The mixture was agitated at below -15C for 30 minutes and then warmed up to normal room temperature (RT) and stirred for 3 hours. 250.0 g (0.61 mol) of the above methyl ester from stage 7, in 250 mL of anhydrous THF, was added over 25 minutes while the temperature was kept below 350C. The light yellow slurry turned to a dark solution. The solution was stirred for 20 minutes. A reaction sample was quenched with MeOH and analyzed by HPLC to make certain that there is no starting methyl ester left. The solution was then cooled back to below 150C. 2.0 L of MeOH was added over 10 minutes while the temperature was kept below 250C followed by 1.0 L of water added in one portion and the mixture was allowed to warm up to room temperature and stir for 15 hours. A reaction sample was analyzed by HPLC to make certain all related intermediates have been converted. The mixture was cooled to below 200C. 1.2 L of 6 N hydrochloric acid was added over 35 minutes while the temperature was kept below 250C. The solution was agitated for 1 hour. The reaction was monitored by HPLC to make certain that all related intermediates had been converted. The solution was cooled to below 150C. 6 N of NaOH was added to adjust the solution pH to 7-8 (about 370 mL was needed). Most solvents (14.5 L) were removed under vacuum (140 mmHg) and 4.0 L of EtOAc and 2.0 L of water were added. Layers were separated and the organic layer was washed with three 2.0 L portions of water and 1.0 L of brine. The solvent was removed under vacuum from the organic layer to yield 450.0 g of a thick dark brown oil as the crude product. The residue was chased with 500 mL of «-propanol to get 393.2 g of a thick slurry. 500 mL of «-propanol was added and the mixture was heated up to 600C to dissolve the solid. The solution was cooled down with agitation and the slurry was filtered after 16 hours at room temperature and the solid was washed with the filtrate and two 100 mL portions of n- propanol and two 200 mL portions of hexane and air dried to yield the title compound (R)- 1,1,1 -trifluoro-4-(5-fluoro-2-methylphenyl)-4-methyl-2-(5H-pyrrolo[3,2-rf]pyrimidin-6- ylmethyl)pentan-2-ol «-propanol solvate as a light yellow solid, 140.2 g, 44% yield.

According to the analysis of related databases, 3438-61-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; BOEHRINGER INGELHEIM PHARMA GMBH & CO. KG; WO2009/134737; (2009); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia