FORM-2
THE PATENTS ACT, 1970 (39 of 1970)
&
THE PATENTS RULE, 2003
COMPLETE SPECIFICATION
[See section 10, rule 13]
An improved process for the preparation of Nicorandil
APPLICANT:
HERBERT BROWN PHARMACEUTICAL & RESEARCH LABORATORIES
W-256/257/258A, M.LD.C. Phase II, Shivaji Udyog Nagar, Dombivli (E)-421203, District- Thane, Maharashtra, India.
Indian Company incorporated under the Companies Act 1956
The following specification particularly describes the invention and the manner in which it is to be performed:

FIELD OF THE INVENTION
The present invention relates to an improved process for the preparation of Nicorandil of Formula I having HPLC purity of more that 99.7%

BACKGROUND OF THE INVENTION
Nicorandil, the nitrate ester of N-(2-hydroxyethyl)nicotinamide, is a vasodilatory drug useful in treatment of various types of angina pectoris whilst causing minimum effects on the dynamics of cardiovascular circulation and on cardiac functions. Nicorandil was first disclosed in US4200640.
Various methods for the preparation of Nicorandil are known, some of these methods are summarized here.
US4200640 discloses a process for preparation of Nicorandil by reacting nicotinoyl chloride with nitric ester of monoethanolamine in presence of pyridine.
ES536328 discloses a process for the preparation of Nicorandil, wherein the process involves oxidation of 3-picoline to nicotinic acid, treatment of nicotinic acid with thionyl chloride followed by ethanolamine to obtain a nicotinamide and nitrating the nicotinamide with the mixture of nitric acid and sulfuric acid to obtain final product.

ES542899 discloses a process for the preparation of Nicorandil by transamidation of nicotinamide with 2-aminoethanol hydrochloride followed by nitration with fuming nitric acid.
ES543857 describes a synthesis method for Nicorandil by nitration of N-(2-chloroethyI)pyridine-3-carboxamide using silver nitrate in acetonitrile at room temperature for 36 hours.
ES534942 describes a process for the preparation of Nicorandil by 3-pyridinecarboxylic acid hydrazide with 2-ammoethylnitrate in presence of mercury oxide.
ES548692 describes a process for the preparation of Nicorandil by treating nicotinic acid methyl ester sequentially with 2-aminoethanol, thionyl chloride, potassium iodide and silver nitrate
IN178880 discloses a process for the preparation of Nicorandil by reacting methyl nicotinate with 2-(nitroxy)ethylamine in 1,2-dimethoxy ethane. The mixture obtained was concentrated and the residue was crystallized using ethanol.
WO2012089769 discloses a process for the preparation of Nicorandil from N-(2-hydroxyethyl)nicotinamide by nitration with a mixture of non-fuming nitric acid, acetic acid and acetic anhydride. The reaction is quenched by using 24% aqueous ammonia.
Furthermore, apart from above discussed references some of the other references related to process for the preparation of Nicorandil are ES549223, PL162496,

R0114613, RU2147577, Indian Journal of Pharmaceutical Sciences 61 (5), 304-305, (1999) and Russian Journal of Applied Chemistry 82(10), 1776-1779, (2009).
As discussed in Chemical & Pharmaceutical Bulletin 32(3), 1064-1070 (1984), Nicorandil is very unstable in acidic and basic conditions. Pharmacopoeial specifications for Nicorandil require more than 99% of HPLC purity with less than 0.1% unknown single maximum impurity, less than 0.1% of inorganic impurities, called "residue on ignition" (ROI) and less than 0.1% of moisture content. Most of the prior art processes carries out reaction in situ which lead to better yield of product however it was our observation that the product obtained are unsatisfactory in terms of its quality.
Furthermore, some processes use silver nitrate as nitrating agent in the course of reaction, however use of such nitrating agent is not feasible on industrial scale due to the high cost and tedious procedures required to treat the reaction mixture and process waste water. Other processes utilize fuming nitric acid or mixture of sulfuric acid and nitric acid as nitrating mixture, both these reagent are strong oxidizer and hence reaction conditions are to be monitored with intense care. The other drawbacks of prior art process include use of toxic reagents like mercury oxide.
In one of the processes described in prior art, after nitration reaction, aqueous ammonia is used for quenching/neutralizing the reaction. Use of ammonia for quenching/neutralizing nitration reaction may lead to formation of ammonium nitrate.
The processes mentioned in prior art suffers from one or more drawbacks. Hence, there is a need to develop an improved, simple, environment friendly, economic and industrially feasible process for the preparation of Nicorandil. The Inventors of present invention have developed an improved process, which provides highly pure

Nicorandil. The Nicorandil prepared using the present invention has HPLC purity of more than 99.7%.
OBJECT OF THE INVENTION
i) An object of the present invention is to provide an improved process for
the preparation of Nicorandil of Formula I, having HPLC purity of more that 99.7%
ii) Another object of the present invention is to provide a process for the preparation of N-(2-hydroxyethyI)nicotinamide of Formula II, having HPLC purity of more that 99%
iii) Another object of the present invention is to provide a process for the preparation of a Nicorandil nitrate salt of Formula III, having HPLC purity of more that 99%
iv) Yet another object of the present invention is to provide a simple, economic, environment friendly and industrially safe process for preparation of Nicorandil
SUMMARY OF THE INVENTION
According to an aspect of the present invention, there is provided an improved process for the preparation of Nicorandil of Formula I, having HPLC purity of more that 99.7%


comprising
a) condensing methyl nicotinate with ethanolamine at 35-80°C for 4 to 6 hours, adding an organic solvent to the reaction mixture, gradually cooling to 0-5°C and maintaining at 0-5°C for 1-2 hours to yield N-(2-hydroxyethyl)nicotinamide of Formula II having HPLC purity of more than 99%

b) nitrating N-(2-hydroxyethyI)nicotinamide of Formula II with 70% nitric acid
in presence of acetic anhydride at 0-3 0°C for 1-3 hours
c) adding an organic solvent to the reaction mixture of step b) and stirring the
mixture at 25-30°C for 1-2 hours to yield Nicorandil nitrate salt of Formula III
having HPLC purity of more than 99%

d) dissolving the Nicorandil nitrate salt of Formula III in water, charcoalizing thus formed solution and adjusting the pH of the solution to 6.5 to 7 using a

weak base like alkali metal carbonates or alkali metal bicarbonates to yield crude Nicorandil of Formula I having HPLC purity of more than 99% e) dissolving the crude Nicorandil of Formula I in an alcohol and recrystallizing by addition of water to yield crystals of Nicorandil of Formula I having HPLC purity of more than 99.7%
DETAILED DESCRIPTION OF THE INVENTION
Nicorandil has coronary vasodilative and coronary vasoconstriction suppressing actions and is useful as a curative for various types of angina pectoris.
The present invention relates an improved process for the preparation of Nicorandil. More particularly, the present invention relates to an improved process for preparation of Nicorandil with HPLC purity of more than 99.7%.
According to an embodiment of the present invention, there is provided an improved process for the preparation of Nicorandil of Formula I, having HPLC purity of more that 99.7%

comprising
a) condensing methyl nicotinate with ethanolamine at 35-80°C for 4 to 6 hours, adding an organic solvent to the reaction mixture, gradually cooling to 0-5°C and maintaining at 0-5°C for 1-2 hours to yield N-(2-hydroxyethyl)nicotinamide of Formula II having HPLC purity of more than

99%

b) nitrating N-(2-hydroxyethyl)nicotinamide of Formula II with 70% nitric acid
in presence of acetic anhydride at 0-30°C for 1-3 hours
c) adding an organic solvent to the reaction mixture of step b) and stirring the
mixture at 25-30°C for 1-2 hours to yield Nicorandil nitrate salt of Formula III
' having HPLC purity of more than 99%

d) dissolving the Nicorandil nitrate salt of Formula HI in water, charcoalizing thus formed solution and adjusting the pH of the solution to 6.5 to 7 using a weak base like alkali metal carbonates or alkali metal bicarbonates to yield crude Nicorandil of Formula I having HPLC purity of more than 99%
e) dissolving the crude Nicorandil of Formula I in an alcohol and recrystallizing by addition of water to yield crystals of Nicorandil of Formula I having HPLC purity of more than 99.7%
The improved process for the preparation of Nicorandil of Formula I can be depicted in Scheme I


According to an embodiment of the present invention, the molar ratio of the ethanolamine used with respect to methyl nicotinate is in the range of I to 1.5
The condensation of methyl nicotinate and ethanolamine is performed in absence of solvent under heating. The reaction mixture is heated to 40-50°C and maintained for 1 hour followed by heating to 60-80°C for 2 to 5 hours. The methanol generated in course of reaction was removed by distillation under vacuum followed by addition of

organic solvent to the reaction mixture. The mixture is cooled to 0-5°C and maintained for 1-2 hours to isolate N-(2-hydroxyethyl)nicotinamide of Formula II having HPLC purity of more than 99%.
The organic solvent used in step a) is selected from chlorinated solvent, ester, ether, alcohol or hydrocarbon, wherein the chlorinated solvent like dichloromethane, ethylene dichloride, chloroform, chlorobenzene, the ester like ethylacetate, the ether like isopropyl ether, dioxane, the alcohol like n-butanol and the hydrocarbon like toluene, hexane is used, preferably ethyl acetate or dichloromethane is used.
The amount of organic solvent used in step a) with respect to methyl nicotinate is in the range of 1 to 3 volumes.
According to another embodiment of present invention, the molar ratio of 70% nitric acid used in step b) with respect to the N-(2-hydroxyethyl)nicotinamide of Formula II is in the range of 2 to 3.
The molar ratio of acetic anhydride used in step b) with respect to the N-(2-hydroxyethylnicotinamide of Formula II is in the range of 4 to 9.
In step b), the nitration is performed by addition of 70% nitric acid to precooled acetic anhydride by maintaining temperature below 5°C to obtain a nitrating mixture. At 0-5°C, N-(2-hydroxyethyl)nicotinamide of Formula II was slowly added to nitrating mixture without allowing temperature to rise. After completion of addition, the mixture was stirred for 1-2 hours at 25-30°C.
According to another embodiment of present invention, the organic solvent used in step c) is selected from chlorinated solvent, ester, ether, alcohol or hydrocarbon,

wherein the chlorinated solvent like dichloromethane, ethylene dichloride, chloroform, chlorobenzene, the ester like ethylacetate, the ether like isopropyl ether, dioxane, the alcohol like n-butanol and the hydrocarbon like toluene, hexane is used, preferably ethyl acetate or dichloromethane is used
The amount of organic solvent used in step c) with respect to the N-(2-hydroxyethyl)nicotinamide of Formula II is in the range of 5 to 8 volumes.
According to another embodiment of the present invention, the amount of water used in step d) with respect to Nicorandil nitrate salt of Formula III is in range of 4 to 10 volumes, preferably 3 to 5 volumes.
The weak base used for adjusting pH in step d) is selected from alkali metal carbonates like sodium carbonate, potassium carbonate or alkali metal bicarbonates like sodium bicarbonate, potassium bicarbonate.
According to yet another embodiment of the present invention, in step e) alcohol like methanol, ethanol, propanol, butanol is used for dissolving crude Nicorandil, preferably methanol is used.
The amount of alcohol used in step e) with respect to Nicorandil nitrate salt of Formula III is in range of 2 to 3 volumes.
The amount of water used in step e) with respect to Nicorandil nitrate salt of Formula III is in range of 3 to 5 volumes.
It was observed by inventors of present invention, use of alcohol-water combination in step e) ensures removal of inorganic and organic impurities/intermediates, which

includes N-(2-hydroxyethyl)nicotinamide of Formula II, 2-(pyridin-3-yl)-4,5-dihydrooxazole of Formula IV and 2-aminoethyl nicotinate of Formula V, to the extent of 0.05%.

The HPLC purity of N-(2-hydroxyethyl)nicotinamide (Formula II) and Nicorandil
nitrate salt (Formula III) is determined using following parameters:
Column : Zorbax Eclipse Plus, C-18, 250mm x 4.6mm, 5u,m
Column temperature : 30°C
Flow rate : 0.8 ml/min
Detection wavelength : 254 nm
Buffer : 0.8 g of Ammonium acetate in 1000 ml of HPLC grade
water and pH adjusted to 3.9 using acetic acid
Mobile phase : Buffer/Acetonitrile (800:200)
Diluent : Mobile phase
Injection volume : 10 μl
Run time : 25 min
Method : Isocratic
The purity of the Nicorandil is determined using following parameters:
Column : Inertsil ODS 3, 250 mm x 4 mm, 5 μm or any equivalent
Column temperature : 25°C
Flow rate : Adjust the flow rate so that the retention time of Nicorandil

is about 18 minutes (About 1.2 ml/min)
Detection wavelength : 254 nm
Mobile phase : Water/ Tetrahydrofuran/ Triethylamine/ Trifluoroacetic acid
(982:10:5:3)
Diluent : Mobile phase
Injection volume : 10 μl
Run time : 55 min.
Method : Isocratic
The detail of the invention provided in the following examples is given by the way of illustration only and should not be construed to limit the scope of the present invention.
EXAMPLES
Example 1:
N-(2-Hvdroxvethyl)nicotinamide (Formula II)
A mixture of 500g of methyl nicotinate and 222.7g of ethanolamine was stirred to obtain a clear solution. The clear solution was heated to 40-50°C and maintained for 1 hour. After 1 hour, mild vacuum was applied, temperature was raised to 70°C and the mixture was maintained at the same temperature for 5 hours. Meanwhile, methanol formed during the reaction was distilled out. The reaction progress was monitored using HPLC. After completion of reaction, the reaction mixture was cooled to 50-60°C and 1000ml of dichloromethane was added. The mixture was then gradually cooled to 0-5°C and maintained at same temperature for 1 hour. The white crystalline precipitate of N-(2-hydroxyethyl)nicotinamide formed was filtered out, washed with dichloromethane and dried under vacuum at 35-40°C. Yield: 508g (83.84%) HPLC purity: 99.58%

Melting point: 88.5°C to 89°C
1H NMR in D20 (δppm): 8.78 (d, IH, Ar-H), 8.59 (d, IH, Ar-H), 8.11-8.09 (m, IH,
Ar-H), 7.50-7.47 (m, IH, Ar-H), 3.72 (t, 2H, -OCH2), 3.49 (t, 2H, -NCH2).
IR (KBr): 3235.39, 3165.29, 3064.99, 2937.98, 2926.11, 2679.21, 2578.91, 2515.26,
1670.41, 1595.18, 1552.75, 1487.17, 1423.51, 1327.07, 1300.07, 1211.34, 1058.96,
1033.88,707.9 cm-1.
Example 2:
N-(2-Hydroxyethyl)nicotinamide (Formula II)
A mixture of 200g of methyl nicotinate and 89.04g of ethanolamine was stirred to obtain a clear solution. The clear solution was heated to 40-50°C and maintained for 1 hour. After 1 hour, mild vacuum was applied, temperature was raised to 70°C and the mixture was maintained at the same temperature for 3.5 hours. Meanwhile, methanol formed during the reaction was distilled out. The reaction progress was monitored using HPLC. After completion of reaction, the reaction mixture was cooled to 50-60°C and 400ml of ethyl acetate was added. The mixture was then gradually cooled to 0-5°C and maintained at same temperature for 1 hour. The white crystalline precipitate of N-(2-hydroxyethyl)nicotinamide formed was filtered out, washed with 100ml of ethyl acetate and dried under vacuum at 35-40°C. Yield: 191.26g (78.92%) HPLC purity: 99.49%
Example 3:
Nicorandil nitrate salt (Formula III)
The 151.44g of acetic anhydride was cooled to 0-5°C and 59.9g of 70% nitric acid was added drop-wise. The temperature was maintained at 0-5°C during the addition. After completion of addition of 70% nitric acid, 50g of N-(2-hydroxyethyl)nicotinamide (Formula II) was slowly added while maintaining the temperature in the range of 0-5°C. The temperature of reaction mixture was then

raised to 25-30°C and the mixture was maintained at the same temperature for \ hour.
The reaction progress was monitored using HPLC. After completion of reaction,
325ml of dichloromethane was added to precipitate Nicorandil nitrate salt & stirred at
25-30°C for 1 hour. The precipitate of Nicorandil nitrate was filtered out, washed
with dichloromethane and dried under vacuum at 35-40°C.
Yield: 72.80g (88.24%)
HPLC purity: 99.07%
Melting point: 105°Cto 106°C
1H NMR in D20 (δppm): 9.13 (d, 1H, Ar-H), 8.91 (d, 1H, Ar-H), 8.87-8.84 (m, 1H,
Ar-H), 8.15-8.12 (dd, 1H, Ar-H), 4.71 (t, 2H, -OCH2), 3.79 (t, 2H, -NCH2).
IR (KBr): 3377.47, 3117.07, 3080.42, 3057.27, 3012.91, 2895.25, 2615.56, 2123.70,
2031.11, 1757.21, 1672.34, 1622.19, 1529.60, 1469.81, 1444.73, 1431.23, 1410.01,
1334.78, 1309.71, 1280.78, 1249.91, 1178.55, 1161.19, 1116.82, 1045.45, 1010.73,
923.93, 904.64, 891.14, 862.21, 823.63, 742.62, 719.47, 677.04 cm-1.
Example 4-6:
Nicorandil nitrate salt (Formula III)
The procedure is carried out as in example 3 except for the molar ratio of acetic anhydride used with respect to N-(2-hydroxyethyl)nicotinamide (Formula II) was changed. The results are given in Table I
Table I

Example No. Molar ratio of acetic anhydride used Yield of Nicorandil nitrate salt obtained HPLC purity of Nicorandil nitrate salt obtained
4 6.5 77.29% 99.40%
5 7 78.81% 99.38%
6 8 75.66% 99.38%

Example 7:
Nicorandil nitrate salt (Formula HI)
The 454.32g of acetic anhydride was cooled to 0-5°C and 180.38ml of 70% nitric acid was added drop-wise. The temperature was maintained at 0-5°C during the addition. After completion of addition of 70% nitric acid, 150g of N-(2-hydroxyethyl)nicotinamide (Formula II) was slowly added while maintaining the temperature in the range of 0-5°C. The temperature of reaction mixture was then raised to 25-30°C and the mixture was maintained at this temperature for 0.5 hour. The reaction progress was monitored using HPLC. After completion of reaction, 975ml of ethylacetate was added to precipitate Nicorandil nitrate salt and stirred at 25-30°C for 1 hour. The precipitate of Nicorandil nitrate was filtered out, washed with ethyl acetate and dried under vacuum at 35-40°C. Yield: 226.10g (91.37%) HPLC purity: 99.41%
Example 8-11:
Nicorandil nitrate salt (Formula III)
The procedure is carried out as in example 7 except for the molar ratio of acetic anhydride used with respect to N-(2-hydrdxyethyl)nicotinamide (Formula II) was changed. The results are given in Table II
Table II

Example
No. Molar ratio of acetic anhydride used Yield ofNicorandil nitrate salt obtained HPLC purity of Nicorandil nitrate salt obtained
8 6 88.45% 99.27%
9 6.5 84.97% 99.33%
10 7 86.90% 99.02%
11 8 87.35% 99.39%

Example 12:
Nicorandil nitrate salt (Formula III)
The 151.44g of acetic anhydride was cooled to 0-5°C and 60.12g of 70% nitric acid was added drop-wise. The temperature was maintained at 0-5°C during the addition. After completion of addition of 70% nitric acid, the mixture was stirred for 0.5 hour and 50ml (1 volume) of pre-cooled ethylacetate was added. The mixture was again cooled to 0-5°C and while maintaining this temperature, 50g of N-(2-hydroxyethyl)nicotinamide (Formula II) was slowly added. The temperature of the reaction mixture was then raised to 25-30°C and was maintained at this temperature for 1 hour. The reaction progress was monitored using HPLC. After completion of reaction, 275ml of ethylacetate was added to precipitate Nicorandil nitrate salt & stirred at 25-30°C for 1 hour. The precipitate of Nicorandil nitrate salt was filtered out, washed with ethyl acetate and dried under vacuum at 35-40°C. Yield: 74.24g (89.9%) HPLC purity: 97.95%
Example 13:
Nicorandil nitrate salt (Formula III)
The procedure is carried out as in example 12 starting with 50g of N-(2-hydroxyethyl)nicotinamide (Formula II) except for, after completion of addition of 70% nitric acid; 100ml (2 volumes) of ethylacetate was added instead of 50ml (1 volume) of ethylacetate. Yield: 84.83% HPLC purity: 98.67%

Example 14: Nicorandil (Formula I)
A clear solution was obtained by dissolving 240g of Nicorandil nitrate salt (Formula
III) in 840ml of water. To the clear solution was then added 12g of activated charcoal
and the mixture was stirred for 1 hour followed by filtration through hyflow bed. The
hyflow bed was washed with 100ml of water. The pH of thus obtained filtrate was
adjusted to 6.5 to 7 with sodium carbonate. The precipitate formed was filtered out to
obtain a wet cake of crude Nicorandil having HPLC purity of 99.78%. The crude
Nicorandil was dissolved in 528ml of methanol and filtered to remove any
undissolved material. The clear filtrate obtained was cooled to 10-15°C and 792ml of
water was slowly added to recrystallize out pure Nicorandil. The crystals of pure
Nicorandil were filtered out, washed with cold water and dried at 25-30°C
Yield: 139g (75.2%)
HPLC purity: 99.99% (single maximum impurity less than 0.1%)
Moisture content (KF): 0.06%
Sulfated ash: 0.05%
Melting point: 93°C
1H NMR in D20 (δppm): 8.8 (d, 1H, Ar-H), 8.63 (dd, 1H, Ar-H), 8.13-8.10 (m, 1H,
Ar-H), 7.52 (dd, 1H, Ar-H), 4.69 (t, 2H, -OCH2), 3.75 (t, 2H. -NCH2).
IR(KBr): 3242.45,3076.56, 1629.90, 1591.33, 1556.61, 1473.66, 1425.44, 1361.79,
1323.21, 1288.49, 1112.96, 1033.88, 898.86, 962.21, 825.56, 754.19, 729.12 cm-1.
ESI Mass: 211.91 (Base peak), 167.60, 125.0.

We claim
1. An improved process for the preparation of Formula I, having HPLC purity of
more that 99.7%

comprising
a) condensing methyl nicotinate with ethanolamine at 35-80°C for 4 to 6 hours, adding an organic solvent to the reaction mixture, gradually cooling to 0-5°C and maintaining at 0-5°C for 1-2 hours to yield N-(2-hydroxyethyl)nicotinamide of Formula II having HPLC purity of more than 99%

b) nitrating N-(2-hydroxyethyl)nicotinamide of Formula II with 70% nitric acid
in presence of acetic anhydride at 0-30°C for 1-3 hours
c) adding an organic solvent to the reaction mixture of step b) and stirring the
mixture at 25-30°C for 1-2 hours to yield Nicorandil nitrate salt of Formula III
having HPLC purity of more than 99%


d) dissolving the Nicorandil nitrate salt of Formula III in water, charcoalizing thus formed solution and adjusting the pH of the solution to 6.5 to 7 using a weak base like alkali metal carbonates or alkali metal bicarbonates to yield crude Nicorandil of Formula 1 having HPLC purity of more than 99%
e) dissolving the crude Nicorandil of Formula I in an alcohol and recrystallizing by addition of water to yield crystals of Nicorandil of Formula I having HPLC purity of more than 99.7%

2. The process as claimed in claim 1, wherein the organic solvent used in step a) and step c) is selected from chlorinated solvent, ester, ether, alcohol or hydrocarbon wherein the chlorinated solvent like dichloromethane, ethylene dichloride, chloroform, chlorobenzene, the ester like ethylacetate, the ether like isopropyl ether, dioxane, the alcohol like n-butanol and the hydrocarbon like toluene, hexane is used, preferably ethyl acetate or dichloromethane is used.
3. The process as claimed in claim 1, wherein the amount of organic solvent used in step a) with respect to methyl mcotinate is in the range of 1 to 3 volumes.
4. The process as claimed in claim 1, wherein the molar ratio of 70% nitric acid used with respect to the N-(2-hydroxyethyl)nicotinamide of Formula II is in range of 2 to 3.
5. The process as claimed in claim 1, wherein the molar ratio of acetic anhydride used

with respect to the N-(2-hydroxyethyl)nicotmarnide of Formula II is in the range of 4 to 9.
6. The process as claimed in claim 1, wherein the amount of organic solvent used in step c) with respect to the N-(2-hydroxyethyl) nicotinamide of Formula II is in the range of 5 to 8 volumes.
7. The process as claimed in claim 1, wherein the weak base used for adjusting pH in step d) is selected from alkali metal carbonates like sodium carbonate, potassium carbonate or alkali metal bicarbonates like sodium bicarbonate, potassium bicarbonate.
8. The process as claimed in claim 1, wherein in step e) alcohol like methanol, ethanol, propanol, butanol is used, preferably methanol is used.
9. The process as claimed in claim 1, wherein the amount of alcohol used with respect to Nicorandil nitrate salt of Formula III is in range of 2 to 3 volumes.
10. The process as claimed in claim 1, wherein the amount of water used in step e)
with respect to Nicorandil nitrate salt of Formula III is in range of 3 to 5 volumes.