With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.25637-16-5,4-Bromotetrahydropyran,as a common compound, the synthetic route is as follows.
4,4?-Di-tert-butyl-2,2?-bipyridine (8.05 mg, 0.03 mmol) and 1,2-dimethoxyethane- dichloronickel (1:1) (5.49 mg, 0.025 mmol) were charged under argon in a flask and suspended in dry 1,2-dimethoxyethane(2 ml). This mixture was sonicated for 5 mm. In a separated microwave vial under argon Iridium( 1+), [4,4?-bis( 1,1 -dimethylethyl)-2,2?-bipyridine-icNl ,icNl ?]bis [3 ,5-difluoro-2- [5-(trifluoromethyl)-2-pyridinyl-icN]phenyl-icC]-, (OC-6-33)-, hexafluorophosphate(1-) (1:1) (CAS 870987-63-6) (5.61 mg,5.00 jimol), N-[5-(7-bromo-4-oxoquinazolin-3 (4H)-yl)-2-(trifluoromethoxy)phenyl] -1 -(4-methylpiperazin-1 -yl)cyclopropanecarboxamide (56.6 mg, 100 jimol), and lithium hydroxide (4.79 mg,200 jimol) were dissolved in 1,2-dimethoxyethane (0.6 ml) and 4-bromotetrahydro-2H-pyran (17 jil, 150 jimol) and 1,1,1,3,3,3-hexamethyl-2-(trimethylsilyl)trisilane (31 jil, 100 jimol) were added under argon. 0.4 ml of the solution of the first flask (catalyst mix) was added to the microwave vial mixture and an argon stream was passed through the resulting mixture for 10 mm. The reaction mixture was irradiated with one 34 W blue LED lamp in the EvoluChemTM PhotoChemistry Device using the 8 x 2 mL vialrack which contains an incorportated fan for cooling to maintain experiment at room temperature. The reaction mixture was then allowed to stir in the device for 15 hours. The reaction mixture was then charged completely on a silica gel column and a chromatographic separation was performed with a gradient of dichloromethane/methanol from 100:0 to 90:10. The material obtained was then purified by preparative RP-HPLC on a 125x30mm with acetonitrile/water (0.2% ammonia) to obtain 25.5 mg (97 % purity, 43 % yield) of the title product.LC-MS (Method 6): R = 1.18 mm; MS (ESIpos): m/z = 572 [M+H]1HNMR (400 MHz, DMSO-d6) [ppm]: -0.008 (2.71), 0.008 (2.39), 1.102 (1.40), 1.115 (3.81), 1.123(4.40), 1.132 (2.09), 1.235 (2.04), 1.245 (4.39), 1.252 (3.56), 1.265 (1.45), 1.714 (0.41), 1.736 (1.31),1.747 (1.12), 1.764 (3.86), 1.774 (5.09), 1.787 (3.43), 1.795 (3.34), 2.157 (0.78), 2.195 (16.00), 2.328(0.72), 2.332 (0.60), 2.366 (0.69), 2.454 (6.05), 2.670 (0.59), 2.980 (0.65), 2.992 (0.73), 3.004 (1.08),3.018 (0.76), 3.030 (0.50), 3.449 (1.27), 3.460 (1.13), 3.477 (2.36), 3.485 (2.44), 3.504 (1.21), 3.512(1.41), 3.972 (2.94), 3.979 (2.01), 3.998 (2.13), 7.366 (2.14), 7.372 (2.14), 7.388 (2.37), 7.394 (2.50),7.531 (2.02), 7.535 (2.22), 7.552 (2.12), 7.555 (2.45), 7.597 (4.28), 7.675 (1.83), 7.679 (1.89), 7.697(1.67), 7.701 (1.58), 8.122 (3.87), 8.142 (3.56), 8.346 (8.33), 8.356 (0.44), 8.582 (3.80), 8.588 (3.82), 10.651 (3.83)., 25637-16-5
As the paragraph descriping shows that 25637-16-5 is playing an increasingly important role.
Reference£º
Patent; BAYER AKTIENGESELLSCHAFT; BAYER PHARMA AKTIENGESELLSCHAFT; JIMENEZ, NUNEZ, Eloisa; BORISSOFF, Julian; HAHN, Michael; DIETZ, Lisa; ZDENKA, GAUGAZ, Fabienne; BENDER, Eckhard; LANG, Dieter; GIESE, Anja; THEDE, Kai; ZORN, Ludwig; BOULTADAKIS ARAPINIS, Melissa; (190 pag.)WO2019/63708; (2019); A1;,
Tetrahydropyran – Wikipedia
Tetrahydropyran – an overview | ScienceDirect Topics