3543-73-5, Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 3543-73-5, name is Ethyl 4-(5-amino-1-methyl-1H-benzo[d]imidazol-2-yl)butanoate, This compound has unique chemical properties. The synthetic route is as follows.
To a solution of 81.3 g (650.6 mmol) 2-bromoethanol, 1 g potassium iodide and 100 g water was added 17.0 g (65 mmol) compound (6). The reaction mixture was heated to 65-70 C. and held at this temperature for 8 h to 12 h. The pH value of the solution was held between 4.2-5.5 during this period by dropwise addition of a solution of 20.0 g (151.4 mmol) diammonium hydrogen phosphate in 35 g water. The control of pH over the duration of the reaction was effected through use of a pH electrode. The conversion was followed by HPLC. The reaction was continued until the fraction of compound (7A) was ?1.5%. Thereby ca. 8% of compound (7B) had formed and the proportion of compound (7) was ca. 87%. The reaction mixture was subsequently concentrated to dryness at ca. 55-60 C. under vacuum. To the residue was added 150 g water and, preferably with an alkali metal carbonate, the pH value adjusted to ca. 8.5. The desired product (7) was extracted with 200 g methylene chloride or 225 g chloroform, and the organic phase subsequently washed with 60-80 g water. The organic phase was then concentrated to dryness and the remaining oil or already crystalline residue dissolved in 200 g ethyl acetate or alternatively in 60 g acetonitrile. Compound (7) crystallised at ca. 5 C. and was filtered under suction, washed with 20 g cold ethyl acetate or alternatively with 15 g cold acetonitrile and dried at 60-70 C. The yield of compound (7) was 18.3 g (52.4 mmol) with a content of ?98.2% (80.5% of theory). The crude contained ?0.6% compound ( 7A) and compound (7B) respectively as well as <0.15% of compound (7C). The crude product obtained was recrystallized from ethyl acetate, or alternatively from acetonitrile, toluene, propan-2-ol, tetrahydrofuran, acetone, isopopyl acetate or water, prior to further conversion to compound ( 8). Thereby the yield of compound (7) was 17.2 g (94.0% recrystallization yield) with a content of >99.2%, wherein compound (7A) was removed below a content of 0.2% and compound (7B) below 0.3%. Through the course of the reaction, the content of compound (7C) was kept below 0.15%, as this compound can only poorly be removed by recrystallization from the above described solvents. The overall yield of this step was 76.5% of theory and was thus ca. 12.5% higher than that described in the procedure using ethylene oxide as according to DD34727 and ca. 31% higher in comparison to the favoured procedure of WO2011079193 involving addition of Huenig’s base.
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Reference:
Patent; Heyl Chemisch-pharmazeutische Fabrik GmbH & Co. KG; Frey, Michael; Walther, Dirk-Detlef; US2014/31560; (2014); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem