Synthetic Route of 866775-18-0, 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. 866775-18-0, name is Methyl 3-amino-6-bromo-5-(trifluoromethyl)picolinate, molecular formula is C8H6BrF3N2O2, 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.
Step 1 : Methyl 3-amino-6-(4-fluorophenyl)-5-(trifluoromethyl)picolinate 3-Amino-6-bromo-5-trifluoromethyl-pyridine-2-carboxylic acid methyl ester (Intermediate 3D) (200 mg, 0.669 mmol), 4-fluorophenylboronic acid (94 mg, 0.669 mmol) and 1 , 1 ‘bis(diphenylphosphoshio)ferrocene palladium dichloride (Apollo) were suspended in THF (2 ml) and 1 M Cs2C03 (0.667 ml). The vial was flushed with N2, sealed and heated at 160C for 15 minutes using microwave radiation. The reaction mixture was partitioned between EtOAc (50 ml) and water (50 ml). The organic portion was separated and washed with brine (30 ml), dried over MgS04, filtered and concentrated in vacuo. Purification by chromatography on silica eluting with 0-80% EtOAc in iso-hexane afforded the title compound; LCMS: Rt = 1 .47 mins, [M+H]+ 315.1 ; Method 2minl_C_v002. Step 2: 3-Amino-6-(4-fluorophenyl)-5-(trifluoromethyl)picolinic acid To a stirred solution of methyl 3-amino-6-(4-fluorophenyl)-5-(trifluoromethyl)picolinate (step 1 ) (6.00 mmol) in EtOH (5 ml) was added 2M NaOH (3 ml, 6.00 mmol) and the solution was stirred at RT for 15 minutes. The resulting mixture was diluted with water (10 ml) and the pH was adjusted to pH 6 using 1 M HCI. The mixture was extracted with DCM (2 x 10 ml) and the phases were separated using a phase separating cartridge. The combined organic extracts were concentrated in vacuo and used in the next step without further purification; LCMS: Rt = 1 .42 mins, [M+H]+ 301.1 ; Method 2minl_C_v002. Step 3: 3-Amino-6-(4-fluorophenyl)-N-(1 H-pyrazol-3-yl)-5- (trifluoromethyl)picolinamide A stirred solution of 3-amino-6-(4-fluorophenyl)-5-(trifluoromethyl)picolinic acid (0.167 mmol) in dry NMP (2 ml) was treated with 1 H-pyrazol-3-amine (0.183 mmol). After stirring at RT, triethylamine (0.366 mmol) was added and stirring continued for 5 minutes. HATU (0.183 mmol) was added and the resulting mixture was sealed and heated at 100 C for 1 hour using microwave radiation. The mixture was partitioned between EtOAc (25 ml) and 1 M NaOH (25 ml). The organic portion was separated, washed with water (25 ml), dried over MgS04 and concentrated in vacuo. Purification by mass directed LCMS eluting with TFA/MeCN/water afforded the title compound as a TFA salt. The salt was partitioned between EtOAc (10 ml) and sodium bicarbonate (10 ml). The organic portion was separated, passed through phase separating cartridge and concentrated in vacuo to afford the title compound; LCMS: Rt = 1 .58 mins, [M+H]+ 366.2; Method 2minLC_v002. 1 H NMR (400MHz, DMSO – d6) delta 12.6 (1 H, s), 10.2 (1 H, s), 7.82 (1 H, s), 7.78 (1 H, s), 7.62 (2H, m), 7.3 – 7.4 (4H, m), 6.72 (1 H, s).
According to the analysis of related databases, 866775-18-0, the application of this compound in the production field has become more and more popular.
Reference:
Patent; NOVARTIS AG; BALA, Kamlesh, Jagdis; BUDD, Emma; EDWARDS, Lee; HOWSHAM, Catherine; LEGRAND, Darren, Mark; TAYLOR, Roger, John; WO2013/38390; (2013); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem