With the rapid development and complex challenges of chemical substances, the synthesis of new drugs is usually one of the most effective ways to increase yield.1514-96-1, name is 4-Chloro-2-(trifluoromethyl)pyrimidine, molecular formula is C5H2ClF3N2, molecular weight is 182.53, as common compound, the synthetic route is as follows.Quality Control of 4-Chloro-2-(trifluoromethyl)pyrimidine
(1) Phosphorus oxychloride (15 mL) was added to 2-trifluoromethyl-4-hydroxypyrimidine (2.50 g) and the mixture was stirred at 60C for 1 hr. The mixture was concentrated under reduced pressure, and a saturated aqueous sodium hydrogen carbonate solution was added to the residue. The mixture was extracted with ethyl acetate. The extract solution was washed with saturated brine, dried and concentrated under reduced pressure to give 2-trifluoromethyl-4-hydroxypyrimidine (0.600 g) as a brown oil.(2) Piperazine (845 mg) was dissolved in DMF (6 mL) with heating and a DMF solution (1 mL) of the above-mentioned compound (597 mg) were added at 40C. The mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated under reduced pressure, and water was added to the residue. The mixture was extracted with chloroform. The extract solution was washed with saturated brine, dried and concentrated under reduced pressure to give 1-(2-trifluoromethyl-4-pyrimidinyl)piperazine (680 mg) as a brown solid.(3) In the same manner as in Example 29(1) and using the title compound (0.832 g) of Reference Example 3 and the above-mentioned compound (0.676 g), 3-{(2S,4S)-1-tert-butoxycarbonyl-4-[4-(2-trifluoromethyl-4-pyrimidinyl)-1-piperazinyl]-2-pyrrolizinylcarbonyl}-1,3-thiazolidine (1.28 g) was obtained as a pale-brown solid.(4) The above-mentioned compound (1.27 g) was dissolved in ethanol (3 mL) and a 4.1 mol/L hydrochloric acid-ethanol solution (3 mL) was added. The mixture was stirred at room temperature for 13 hr. The reaction solution was concentrated under reduced pressure, and ethyl acetate was added to the residue. The precipitate was collected by filtration to give the title compound (1.02 g) as a white solid.1H-NMR(DMSO-d6) delta 2.15-2.33(1H,m), 2.90-4.05(16H,m), 4.45-4.78(3H,m), 7.24(1H,d,J=6.3Hz), 8.45(1H,d,J=6.3Hz), 9.12(1H,brs), 10.83(1H,brs), 12.7(1H,brs).
At the same time, in my other blogs, there are other synthetic methods of this type of compound,1514-96-1, 4-Chloro-2-(trifluoromethyl)pyrimidine, and friends who are interested can also refer to it.
Reference:
Patent; Mitsubishi Pharma Corporation; EP1426366; (2004); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia