Electric Literature of 57381-37-0, 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. 57381-37-0 name is 2-Bromo-5-chlorobenzonitrile, This 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.
Example 50 : (R)-4 ‘-( 4-Amino-8-methyl-5-oxo-7,8-dihvdropyrimido [5,4- f| [ 1 ,41 oxazepin-6( 5H)-yl)-4-chloro-2 ‘-fluor obiphenyl-2-carbonitrile; (i~)-4-Amino-6-(3-fluoro-4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)phenyl)-8- methyl-7,8-dihydropyrimido[5,4-f][l ,4]oxazepin-5(6H)-one (Intermediate 51 ; 290 mg, 0.70 mmol), PdCl2(dppf)-DCM adduct (28.6 mg, 0.04 mmol), potassium phosphate (0.07 mL, 0.84 mmol) and 2-bromo-5-chlorobenzonitrile (182 mg, 0.84 mmol) were suspended in DME (3 mL), ethanol (1.5 mL) and water (0.75 mL) and sealed into a microwave tube, degassed under vacuum and the atmosphere replaced with nitrogen. The reaction was heated to 130 C for 90 minutes in the microwave reactor and cooled to RT. The reaction mixture was evaporated to dryness and redissolved in methyl THF (25 mL), and washed sequentially with water (25 mL) and saturated brine (25 mL). The organic layer was dried over Na2SC”4, filtered and evaporated to afford crude product. The crude product was purified by preparative HPLC (Waters XBridge Prep CI 8 OBD column, 5mu silica, 50 mm diameter, 150 mm length), using decreasingly polar mixtures of water (containing 0.1% formic acid) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford the title compound (74.0 mg, 24.94 %) as a white solid. 1H NMR (400 MHz, CDC13, 30C) 2.61 (3H, s), 3.89 – 4.00 (2H, m), 4.86 – 5.08 (1H, m), 5.51 – 5.74 (1H, m), 7.22 (1H, d), 7.49 (2H, dd), 7.66 (1H, dd), 7.78 (1H, d), 7.82 – 8.07 (1H, m), 8.33 (1H, s). m/z (ES+), (M+H)+ = 424
At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Bromo-5-chlorobenzonitrile, and friends who are interested can also refer to it.
Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; BIRCH, Alan, Martin; GOLDBERG, Frederick, Woolf; LEACH, Andrew; WO2011/121350; (2011); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts