At the same time, in my other blogs, there are other synthetic methods of this type of compound,1088994-22-2, 5-Methyl-2-(pyrimidin-2-yl)benzoicacid, and friends who are interested can also refer to it.
Adding a certain compound to certain chemical reactions, such as: 1088994-22-2, 5-Methyl-2-(pyrimidin-2-yl)benzoicacid, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound, HPLC of Formula: C12H10N2O2, blongs to pyrimidines compound. HPLC of Formula: C12H10N2O2
2- { 2- ((2R,5R)-5 – ( [Y5~Fiuoropyridin-2 -vDoxyjmethyl } -2-methy Ipiperidin- 1 -vDcarbonyl] -4- methylphenvUpyrimidine (5To a 2 L round bottom flask, equipped with over head stirrer, thermocouple, dropping funnel, and nitrogen inlet, was charged biaryl acid 3 (43.10 g, 1.05 equiv), 2,6- dimethylpyridine (23.15 mL, 1.05 equiv) and DMF (250 mL, 5 V) and was cooled to 5 C. Then, trimethyl acetyl chloride (Piv-Cl) (24.45 mL) was slowly added at 5-10 C. The reaction was stirred at 10 C for 0.5 h. Amine-HCl salt 4 (50.00 g) and 50 wt% T3P in DMF (5.96 g, 5 mol%) were added at 10-15 C, respectively. The reaction mixture was stirred at 20-25 C for 1- 2 h (typical > 76 A% conversion), 2,6-lutidine (22.05 mL, 1.0 equiv) was slowly added over 0.5 h, the reaction mixture was stirred at rt for 3-5- h (> 95 A% conversion). The reaction can be also carried out as follows. To a 2 L round bottom flask, equipped with overhead stirrer, thermocouple, dropping funnel, and nitrogen inlet, was charged biaryl acid 3 (43.10 g, 1.05 equiv), 2,6-dimethylpyridine (45.2 mL, 2.05 equiv), amine-HCl salt 4 (50.00 g), 50 wt% T3P in DMF (5.96 g, 5 mol%)and DMF (250 mL, 5 V) and the resulting mixture was cooled to 15 C. Then, Piv-Cl (24.45 mL) was slowly added at 15-25 C. After complete addition of Piv-Cl, the reaction mixture was aged at 20-25 C for 3-5 h (>95 A% conversion).10 mol% of 2,6-lutidine (2.21 mL) and 10 mol% of Piv-Cl (2.45 mL) were added at rt, respectively. The reaction mixture was stirred at room temperature for 8-16 h (98.5 A% conversion). The reaction mixture was diluted with toluene (500 mL, 10 volume) and water (250 mL, 5 V) at 10-20 C. The reaction mixture was stirred at 10-20 C for 0,5 h. After phase separation, the aqueous layer was extracted with toluene (250 mL x 1, 5 volumes). The combined organic layer was washed with water (200 mL x 1, 4 volumes), 1 N NaOH (200 mL x 1, 4 volumes), and 16% brine (100 mL x 1, 2 volumes).The resulting toluene solution was filtered through 20 wt% of Aquagard activated carbon (14.8 g, equal to 20 wt% of assay product), which was held on solka flock (16 g). The cake was rinsed with toluene (400 mL, 8 volumes)The combined filtrates were concentrated to 150 mL (total volume). At this point, tert-butylbenzene (70 mL) was added dropwise. The resulting solution was solvent-switched to tert-butylbenzene (200 mL, total volume). Crystalline solid 5 was formed during solvent-switch. The resulting slurry was heated to 90-95 C to become homogenous solution. The resulting solution was cooled to 80 C and was seeded with 2% desired crystalline form of 5. The slurry was aged at 80 C for 2 h, and then was slowly cooled to 60 C over 10 h, and from 60 to 20 C over 10 h. The resulting slurry was aged at 20 for 24-48 h. The crystalline solid was collected by filtration, rinsed with tert-butylbenzene (50 mL), n-heptane (100 mL), dried under vacuum with nitrogen sweep and gave 2-{2-[((2ii,5ii)-5-{[(5-fiuoropyridin-2-yl)oxy]methyl}-2- methylpiperidin-l-yl)carbonyl]-4-methylphenyl}pyrimidine (5) (66.85 g, 88% isolated yield).
At the same time, in my other blogs, there are other synthetic methods of this type of compound,1088994-22-2, 5-Methyl-2-(pyrimidin-2-yl)benzoicacid, and friends who are interested can also refer to it.
Reference:
Patent; MERCK SHARP & DOHME CORP.; FENG, Yun Shao; MOSES, Anthony; ZHONG, Yong-Li; WO2012/58129; (2012); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia