|
Developed by Pfizer Inc. (Pfizer) , a new generation of treatment of cardiovascular disease drug amlodipine is the third generation of 1,4 - a typical representative of the dihydropyridine calcium antagonist , has been on sale in dozens of countries and regions all over the world . Because of its efficacy , antihypertensive effect lasting security , after the listing market much favor , still the world one of the best-selling drug . The L- amlodipine calm dextral amlodipine amlodipine both enantiomers , the former have a blood pressure lowering effect , while the latter did not even have side effects . Therefore , obtained by splitting levamlodipine (Levamlodipine) is more effective and safer than amlodipine antihypertensive drugs . By analyzing the contrast known amlodipine synthesis and chiral separation process , we have developed a large-scale production for the domestic route . Phthalic anhydride and ethanolamine as the main raw material , amino protection , etherification , ammoniated , condensation , cyclization , deprotection ammonia amlodipine ; by chiral separation into salt synthesis benzenesulfonate L- amlodipine ; preliminary design and the sulfonic acid levamlodipine tablet prescription . Because the benzenesulfonic levamlodipine the preparation process , the chiral separation of amlodipine is a critical step , so we mainly by orthogonal test of the split of the key factors of intensive research . Found in the study , in chiral separation amlodipine process , the solvent of choice opponents split tremendous impact , the chiral separation of amlodipine domestic the patent main difference is the use of different solvents . Experimental comparison , we chose an unreported amlodipine split solvent , N-2 - methyl - pyrrolidone , using the solvent split the proceeds of L- amlodipine specific rotation, optical purity , in line with the national pharmacopoeia requirements , and the yield can reach 80% . By optimizing Amlodipine tie split process we get more mature and reliable , more suitable for the requirements of large-scale production , initially developed by the sulfonic acid levamlodipine piece of the prescription and production process also provides reference for industrial production quality standards in line with the national pharmacopoeia requirements . The above work as benzenesulfonic levamlodipine synthesis of bulk drugs and tablet preparation has accumulated a wealth of experience , and conducive to the industrial production .
|