A common compound: 26663-77-4, name is Methyl benzimidazole-5-carboxylate, belongs to imidazoles-derivatives compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below. 26663-77-4
tert-butyl-2-chloro-4-fluorobenzoate (200 mg, 0.867 mmol), methyl lH-benzimidazole-5- carboxylate (214 mg, 1.214 mmol) and potassium carbonate (359 mg, 2.60 mmol) in dry acetonitrile (12 mL) was stirred at 85C for 6 h. The reaction mixture was cooled to RT and the solid was filtered and washed with EtOAc. The filtrate was concentrated and purified by flash chromatography (ISCO CombiFlash system, 80g Silica gel column, 0-60% EtOAc in hexane as as eluting solvent) to afford the product as a mixture of two regioisomers. Further separation of this mixture of products by SFC technique on chiral AD-H column and using 55% MeOH/C02 as mobile phase yielded compound 18A-a, methyl l-(4-(tert-butoxycarbonyl)-3-chlorophenyl)- lH-benzo[d]imidazole-6-carboxylate, and compound 18A-b, methyl l-(4-(tert-butoxycarbonyl)- 3- chlorophenyl)-lH-benzo[d]imidazole-5-carboxylate. For compound 18A-a: methyl 1 -(4-(tert-butoxycarbonvD-3 -chlorophenvD- 1 H- benzo[dlimidazole-6-carboxylate (M+H) calc. = 387.10; found = 387.15. 1H NMR (500 MHz, CD3OD): delta 8.70 (s, br, 1 H); 8.30 (s, br, 1 H); 8.08 (dd, J = 1.5 Hz, J = 8.5 Hz, 1 H); 8.01 (d, J = 8.5 Hz,l H); 7.89 (d, J = 2.5 Hz,l H); 7.86 (d, J = 8.5 Hz, 1 H); 7.74 (dd, J = 2.0 Hz, J = 8.5 Hz, 1 H); 3.95 (s, 3H); 1.66 (s, 9H) For compound 18A-b: methyl 1 -(4-(tert-butoxycarbonyl)-3 -chlorophenyD- 1 H- benzo[dlimidazole-5-carboxylate (M+H) calc. = 387.10; found = 387.15. 1H NMR (500 MHz, CD3OD): delta 8.56 (s, br, 1 H); 8.47 (s, br, 1 H); 8.12 (dd, J = 1.5 Hz, J = 8.5 Hz, 1 H); 8.10 (d, J = 8.5 Hz,l H); 7.89 (d, J = 2.0 Hz,l H); 7.76 (d, J = 8.5 Hz, 1 H); 7.73 (dd, J = 2.0 Hz, J = 8.5 Hz, 1 H); 3.97 (s, 3H); 1.65 (s, 9H) Additional NMR studies (NOE) confirmed the structure assignments of the two products.
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, 26663-77-4, other downstream synthetic routes, hurry up and to see.
Reference:
Patent; MERCK SHARP & DOHME CORP.; MOCHIDA PHARMACEUTICAL CO., LTD.; ZHANG, Ting; CHEN, Yi-Heng; GUO, Liangqin; HRUZA, Alan; JIAN, Tianying; LI, Bing; MENG, Dongfang; PARKER, Dann, L., Jr.; SHERER, Edward, C.; WOOD, Harold, B.; SAKURADA, Isao; (130 pag.)WO2016/94260; (2016); A1;,
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