With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.62071-40-3,4-(Tetrahydropyran-4-yl)phenylamine,as a common compound, the synthetic route is as follows.
The mixture of 4,6-dichloronicotinonitrile (440 mg, 2.5 mmol), 4-(tetrahydro-2H-pyran-4-yl)aniline (530 mg, 3.0 mmol), DIEA (0.65 mL, 3.75 mmol) in 20 mL DMF was stirred at 90 C. for overnight to afford a mixture of compounds 139.3 (UV=316 nm) and 139.4 (UV=278 nm). The mixture was concentrated in vacuo and subjected to flash column (0-20% EtOAc in DCM) to isolate the 139.3/139.4 product (870 mg). This product mixture (500 mg, 1.6 mmol) was dissolved in 100 mL MeOH with 9 mL DMSO, and was stirred at RT. To it was added K2CO3 powder (440 mg, 3.2 mmol) and then H2O2 (50 wt %, 3 mL). The mixture was stirred at RT for 2 h. It was diluted with 200 mL EtOAc, filtered through celite and concentrated in vacuo. It was subjected to reverse phase prep HPLC to isolate product 139.5 (UV=278 nm) and product 139.6 (UV=287 nm). Compound 139.5 (50 mg, 0.15 mmol) was dissolved in 2 mL in a sealed tube. To it were added 4-aminotetrahydropyran (76 mg, 0.75 mmol) and DIEA (80 muL, 0.45 mmol). The mixture was stirred at 120 C. for 2 days. It was cooled to RT, treated with 0.2 ml, TFA, and subjected to reverse phase prep HPLC to isolate the title compound (48 mg). MS found for C22H28N4O3 as (M+H)+ 397.3. UV: lambda=258 nm. 1H NMR: (CD3OD) delta 8.11 (1H, s), 7.38 (2H, dt, J=8.0; 1.6 Hz), 7.26 (2H, dt, J=8.0; 2.0 Hz), 6.03 (1H, s), 4.05 (2H, m), 3.93 (2H, m), 3.66 (1H, m), 3.61-3.51 (4H, m), 2.86 (1H, m), 1.98 (2H, m), 1.80 (4H, m), 1.61 (2H, m) ppm., 62071-40-3
As the paragraph descriping shows that 62071-40-3 is playing an increasingly important role.
Reference£º
Patent; Portola Pharmaceuticals, Inc.; US2012/108566; (2012); A1;,
Tetrahydropyran – Wikipedia
Tetrahydropyran – an overview | ScienceDirect Topics