ChemicalBook CAS DataBase List Ivabradine hydrochloride

Ivabradine hydrochloride synthesis

12synthesis methods

Product Name:Ivabradine hydrochloride
CAS Number:148849-67-6
Molecular formula:C27H37ClN2O5
Molecular Weight:505.05

3-[3-[[[(7S)-3,4-DiMethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]Methyl]MethylaMino]propyl]-1,3-dihydro-7,8-diMethoxy-H-3-benzazepin-2-one

1086026-31-4
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148849-67-6
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Yield:148849-67-6 93.5%

Reaction Conditions:

Stage #1: 3-{3-[{[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}-(methyl)amino]propyl}-7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-onewith palladium 10% on activated carbon;hydrogen;acetic acid at 15 - 25; for 23 h;
Stage #2: with hydrogenchloride in ethyl acetate;isopropyl alcohol at 0 - 10; for 1 h;

Steps:

3; 4 Steps:

567 g of the dehydrogenated ivabradine obtained in Example 1 was added to the reaction flask.2.55L glacial acetic acid,141g palladium on carbon,Stir well and cool to 20±5°C.After vacuuming, the nitrogen was replaced 3 times.Hydrogen replacement 3 times; control temperature 15~25 ° C, atmospheric hydrogen After 23 hours of reaction in the environment.The mixture was filtered through celite, and the filter cake was rinsed with glacial acetic acid.Purified water and ethyl acetate were added to the oil, stirred well, and the pH was adjusted to 9 to 10 with a sodium hydroxide solution. Liquid separation, water phaseExtracted with ethyl acetate, combined with organic phase, washed with saturated sodium bicarbonate, washed with saturated sodium chlorideAfter stirring and drying overnight, suction filtration, the filter cake was rinsed with ethyl acetate, and the filtrate was spun dry to obtain 403.9 g of ivabradine, the yield was 70.9%.HPLC purity: 96.3%. Into a 10 L reaction flask was placed 402 g of ivabradine, 6 L of ethyl acetate,Stir until fully dissolved,Cool down to 0~10 °C,Add 172.2gHydrogen chloride isopropanol solution (20wt%),A large amount of white solid is precipitated,Stir for 1 hour,Filtered, the filter cake was rinsed with ethyl acetate.The material was vacuum dried for 15 hours to obtain a white solid pulverized ivabradine 405.1 g,Yield 93.5%, HPLC purity: 99.8%.

References:

CN108424390,2018,A Location in patent:Paragraph 0057; 0059-0062; 0063-0069