Reference of 1174321-06-2, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 1174321-06-2, name is 5-(Difluoromethyl)pyrazine-2-carboxylic acid belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.
General Procedure A: the coupling of anilines prepared in Preparation Examples 25- (14) and 26-Q2) with aryl carboxylic acidsThe aniline (100 mg) was dissolved in DCM (2 mL) and the aryl carboxylic acid (1.2 – 1.6 equiv.), N,N-diisopropylethylamine (3 equiv.) and (lH-benzotriazol-1- yloxy)tripyrrolidin-l-yl)phosphonium hexafluorophophate (1.2 – 1.6 equiv.) were added. The reaction mixture was stirred at RT for 16 h – 3 days, and sodium bicarbonate (sat., aq., 25 mL) was added. The mixture was extracted with EtOAc (2 x40 mL), the combined organic portions were dried over MgSO4, evaporated and purified by silica gel chromatography (EtOAc/hexanes gradient) to afford the amide as a white solid. The amide was dissolved in DCM (2 mL) and TFA (1 mL) was added. After stirring at RT for 1-3 h, the reaction mixture was evaporated and sodium bicarbonate (sat., aq., 25 mL) was added. The mixture was extracted with EtOAc (2 x 40 mL), and the combined organic portions dried over MgSO4 and evaporated to afford the desired compound as a white solid. On occasions where the product was not pure, purification was effected by silica gel chromatography (MeOH/EtOAc/DCM gradients). Example 1 : N-(3-((‘4aR,5S,7aS)-2-amino-5-(‘fluoromethyl)-4a,5,7,7a-tetrahvdro-4H- furor3,4-diri,31oxazin-7a-yl)-4-fluorophenyl)-5-(difluoromethyl)pyrazine-2- carboxamideSynthesized from tert-butyl [(4aR,5S,7aS)-7a-(5-amino-2-fluorophenyl)-5- fluoromethyl-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][l,3]oxazin-2-yl]carbamate 25-(14) and 5-difluoromethyl-pyrazine-2-carboxylic acid according to General Procedure A. 1H NMR (400 MHz, CDCl3) delta (ppm): 2.94 (d, /=7.8 Hz, IH), 3.79 (dd, /=8.6, 2.5 Hz, IH), 3.89 – 4.05 (m, 2H), 4.28 – 4.66 (m, 4H), 6.72 (t, J 54.3 Hz, IH), 7.05 (dd, /=11.6, 8.8 Hz, IH), 7.67 (dd, /=7.1, 2.8 Hz, IH), 7.91 – 8.03 (m, IH), 8.85 (s, IH), 9.45 (s, IH), 9.61 (br s, IH)
In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles, 5-(Difluoromethyl)pyrazine-2-carboxylic acid, other downstream synthetic routes, hurry up and to see.
Reference:
Patent; EISAI R&D MANAGEMENT CO., LTD; ELLARD, John Mark; FARTHING, Christopher Neil; HALL, Adrian; WO2011/9898; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem