We Claim:
I. A process for preparation of 7,8-dimethoxy-l,3-dihydro-2H-3-benzazepine-2-one of
compound of Formula I;
Formula I
i) reacting (3,4-dimethoxyphenyl)acetic acid, compound of Formula III,
Formula III
with N-(2,2-dimethoxyethyl)amine at a suitable temperature in absence of a solvent and
condensing agent to give N-(2,2-dimethoxyethyl)-2-(3,4-dimethoxyphenyl) acetamide of
compound of Formula V;
Formula V
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ii) cyclizing the resulting N-(2,2-dimethoxyethyl)-2-(3,4-dimethoxy phenyl)acetamide
of compound of Formula V in the presence of acid; and
iii) isolating 7,8-dimethoxy-l ,3-dihydro-2H-3-benzazepine-2-one compound of
Formula 1.
2. The process as claimed in claim 1, wherein in step i) the suitable temperature is from
100°Cto 140°C.
3. The process as claimed in claim 1, wherein in step ii) the acid is Hydrochloric acid,
acetic acid, sulphuric acid, methanesulfonic acid or a mixture thereof
4. The process as claimed in claim 1, wherein in step ii) the suitable temperature is from
20°C to 30°C.
5. A process for the preparation of Ivabradine of compound of Formula-II
PATENT OFFICE CHENNAI 0 2 / O 7 r 2 0 2 4 1 5'2 1
Formula II
or its pharmaceutically acceptable salt thereof which comprises:
i) reacting (3,4-dimethoxyphenyl)acelic acid of compound of Formula III,
Formula Hl
with N-(2,2-dimethoxyethyl)amine at a suitable temperature in absence of a solvent and
condensing agent to give N-(2,2-dimethoxyethyl)-2-(3,4-dimethoxyphenyl) acetamide of
compound of Formula V;
Formula V
ii) cyclizing the resulting N-(2,2-dimethoxyethyl)-2-(3,4-dimethoxy phenyl)acetamide
of compound of Formula V in the presence of a suitable acid to obtain compound of
Formula I; as claimed in Claim l
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PATENT
Formula I
iii) alkylating 7,8-dimethoxy-l,3-dihydro-2H-3-benzazepine-2-one of compound of
formula I with l-bromo-3-chloro-propane in presence of a suitable base in a organic
solvent to obtain 7,8-dimethoxy-3-[3.-chloropropyl]-l,3-dihydro-2H-3-benzazepin-
2- one of compound of Formula VI;
Formula VI
iv) compound of Formula VI treated with Iodinating agent in presence of organic solvent
to obtain 7,8-dimethoxy-3-[3-iodo propyl]-l,3-dihydro-2H-3-benzazepin-2-one
compound of Formula VII;
OFFICE CHENNAI 0 2 /0 J ' 20 2 4 1 5: 2 1
Formula VII
v) condensing the compound of Formula VII with Formula VHl or salt thereof,
Formula VIII
in suitable solvent to obtain compound of Formula IX or salts;
Formula IX
vi) catalytic hydrogenation of compound of Formula IX to prepare Ivabradine; and
vii) converting Ivabradine into Ivabradine pharmaceutically acceptable salt thereof by
reacting with a suitable acid.
6. The process as claimed in claim 5, wherein in step iii) the suitable base is potassium
tertiary butoxide, alkali metal hydroxide such as sodium hydroxide, potassium
hydroxide; the organic solvent is acetone, dimethylsulfoxide, dimethylformamide or
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PATENT
mixtures thereof.
7. The process as claimed in claim 5, wherein in step iv) iodinating agent is sodium iodide;
step v) condensation is carried out in the presence of a base and solvent; step vi)
reduction is carried out using palladium on carbon catalyst in suitable solvent under
hydrogen pressure of 2.5-3.5 kg/cm; in step vii) Ivabradine is converted to suitable acid by reacting with a suitable acid in a suitable solvent.