Process for the preparation of anti-ischemic and anti-hypertensive drug
amlodipine besylate [2-{(2-aminoethoxy)-methyl-4-(2-chlorophenyl) 3-ethoxy
carbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine} benzene
sulphonate]. Phthalic anhydride is condensed with monoethanol amine at
150-190.degree. C. The resulting N-(2-hydroxyethyl) phthalimide is coupled
with 4-chloroethyl acetoacetate in the presence of sodium hydride in an
organic solvent in an inert atmosphere at -11 to -15.degree. C.
Ethyl-4-[-2(phthalimido) ethoxy] acetoacetate formed is coupled with
orthochloro benzaldehyde in the presence of pyridine salt at 70-90.degree.
C. Ethyl-2-(2-chloro benzylidine)4-[-2(phthalimido) ethoxy] acetoacetate
fanned is condensed with methyl amino crotonate at 20-40.degree. C. in the
presence of acetic acid to form phthaloyl amlodipine
[2-(2-Phthalimidoethoxy) methyl-3-carboethoxy
1(chlorophenyl)-S-carbomethoxy-6-methyl-1,4-dihydropyridin] which is
purified by dissolving in an organic solvent in the ratio 1:2-1:5 w/v and
precipitated by the addition of water at 35-60.degree. C. Purified
phthaloyl amlodipine is hydrolysed with methylamine in the presence of a
protic solvent at 20-50.degree. C. Amlodipine base [2-(aminoethoxy)
methyl-3-carboethoxy-4-(2-chlorophenyl)-5-carbomethoxy-6-methyl-1,4-dihydr
opyridin] formed is reacted with benzene sulfonic acid. The resulting
amlodipine besylate is purified in an organic solvent at 30-70.degree. C.
and precipitated by the addition of an insoluble solvent.
Процесс для подготовки сульфоната анти-iwemicnyx и anti-hypertensive снадобья amlodipine besylate [ 2-{(2-aminoethoxy)-methyl-4-(2-chlorophenyl) 3-ethoxy carbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine} коксобензола ]. Фталиевый ангидрин сконденсирован с амином monoethanol на 150-190.degree. Ч. Приводя к N-(2-hydroxyethyl) фталимид соединен с acetoacetate 4-chloroethyl in the presence of гидрид натрия в органическом растворителе в инертной атмосфере на -11 к -15.degree. Ч. Сформированное acetoacetate ethoxy 3tila-4$-[-2(phthalimido) ] соединено с бензальдегидом orthochloro in the presence of соль пиридина на 70-90.degree. Дуют acetoacetate ethoxy C, котор Ethyl-2-(2-chloro benzylidine)4-[-2(phthalimido) ] сконденсировано с метиловым амино crotonate на 20-40.degree. C in the presence of укусная кислота для того чтобы сформировать amlodipine phthaloyl [ 2-(2-Phthalimidoethoxy) methyl-3-carboethoxy й(чюлоропюеныл)-С-чарбометюохы-6-metilovoe-1.4-dihydropyridin ] очищено путем растворять в органическом растворителе в коэффициенте 1:2-1:5 w/v и осаждено добавлением воды на 35-60.degree. C Очищенное amlodipine phthaloyl hydrolysed с метиламином in the presence of protic растворитель на 20-50.degree. C сформированное opyridin основания Amlodipine [ 2-(aminoethoxy) methyl-3-carboethoxy-4-(2-chlorophenyl)-5-carbomethoxy-6-methyl-1,4-dihydr ] прореагировано с кислотой коксобензола сульфоновой. Приводя к besylate amlodipine очищено в органическом растворителе на 30-70.degree. Ч. и осаждено добавлением неразрешимого растворителя.
