Title of Invention	NOVEL PROCESS FOR THE PREPARATION OF MONTELUKAST SALTS
Abstract	Montelukast n-butyl amine compound having the formula in a crystalline solid form

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Novel Salts of Montelukast K O O CN LU CT o Field of the Invention The present invention relates to a novel organic amine salts of l-[[[(lR)-l-[3- [(lE)-2 Formula-1 Further more the present invention relates to the process for the preparation of pure l-[[[(lR)-l-[3-[(lE)-2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-[2-(l-hydroxy-l- methylethyl)phenyl] propyl]thio]methyl]cyclopropaneacetic acid sodium salt (montelukast sodium) compound of formula-2, Formula-2 Montelukast sodium is a leukotriene D4 antagonist, montelukast sodium is indicated for the prophylaxis and chronic treatment of asthma in adults and pediatric patients. It is also indicated for the relief of symptoms of seasonal allergic rhinitis and for perennial allergic rhinitis in adults and pediatric patients, montelukast sodium salt is available in a number of oral formulations including tablets, chewable tablets and oral granules. Bacl^round of the Invention EP 480717 discloses a process for the synthesis of montelukast and its pharmaceutically acceptable salts especially sodium. The process for the preparation comprises of reacting [(E)]-2-(2-(2-(3(S)-(3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)-3-(methanesulfonyloxy) propyl)phenyl)-2-propoxy) tetrahydropyran with methyl 1-(acetylthiomethyl) cyclopropane acetate in presence of hydrazine^ cesium carbonate in acetonitrile as a solvent to get methyl ester of montelukast in pyran protected form. The protected compound is further reacted with pyridinium p-toluene sulfonate, sodium hydroxide in a mixture of methanol and tetrahydrofliran as a solvent to afford montelukast sodium of Formula-2. US 5,614,632 disclose the preparation of l-(mercapto methyl) cyclopropane acetic acid, which is a key intermediate for the preparation of montelukast sodium. The said patent claimed an improved process for the preparation of montelukast sodium including the process for the preparation of its key intermediates. The process comprises, the generation of dilithium dianion of l-(mercaptomethyl) cyclopropaneacetic acid and then condensation with [(E)]-2-(2-(2-(3(S)-(3"(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)-3 -(methanesulfonyloxypropyl)phenyl)-2-propanol (referred as mesylated alcohol) to afford the montelukast. It is further converted to its corresponding sodium salt via dicyclohexyl amine salt. The patent also discloses the process for the preparation of mesylated alcohol, which comprises reacting methyl 2-(3 (S)-(3"(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)-3-hydroxy propyl) benzoate with methyl magnesium chloride to give diol, which is further converted to mesylated alcohol on reaction with methane sulphonyl chloride. The process for the preparation of above described benzoate is disclosed in EP 480717 (example 146, step-2). Further the main drawback of the prior art processes is that it describes a process for preparation of montelukast sodium via the dicyclohexylamine salt which needs to be further purified before conversion to the sodium salt. The dicyclohexylamine salt is highly hygroscopic in nature which leads to problems in isolation of the product. The hygroscopic nature of these salts results in powder handling issues at various stages, for example during filtration, isolation, drying and formulation, thereby limiting the scope for achieving high purity and industrial applicability. It was the aim of the present invention to develop an improved process for preparation of montelukast that would provide pure substance possessing high advantageous physico-chemical properties, high degree of crystallinity and thermodynamic stability, and therefore having appropriate processing parameters facilitating its formulation into the pharmaceutical dosage forms. The aim of the invention has been achieved by obtaining novel organic amine sahs of montelukast. Brief description of the Invention Accordingly, the first aspect of the present invention provides a novel organic amine salts of montelukast like n-butyl amine, isobutyl amine and (+/-)-5'ec-butyl amine. The novel salts of montelukast are readily isolable in a substantially crystalline form and may by used for the preparation of pure montelukast and/or its pharmaceutically acceptable salts like sodium. The second aspect of the present invention is to provide a process for the preparation of novel organic amine salt of montelukast sodium comprises of a) reacting the diol compound of formula-3 Formula-3 with methane sulphonyl chloride in presence of a suitable organic solvent or mixtures thereof to give methane sulfonate compound of formula-4, Formula-4 which in-situ reacting with l-(mercaptomethyl)cyclopropane methyl ester compound of formula-5 Formula-5 in presence of polar aprotic solvent with or without combination of CrC4 alcohol and in presence of a strong base like alkali or alkaline earth metal alkoxide, followed by treating the obtained compound with organic amine like n-butyl amine, isobutyl amine and (H^ysec-hntyl amine in a suitable non-polar organic solvents and/or keto solvents and/or ester solvents followed by seeding with corresponding organic amine salt of montelukast compound gives corresponding montelukast organic amine salt compound of formula-1, Formula- 1 Optionally purifying the Montelukast organic amine salt compound of formula-1 using suitable solvent. The third aspect of the present invention is to provide the use of novel organic amine salts of montelukast in the preparation of pure montelukast and/or its pharmaceutically acceptable salts. The process for the preparation of pure montelukast and/or its pharmaceutically acceptable salts comprises a) Converting the novel organic amine salt like n-butyl amine, isobutyl amine and ^ec"butyl amine of montelukast compound of formula-1 into its pharmaceutically acceptable sah compound of formula-2 by treating with sodium source in a suitable solvent. Advantages of the present invention. • Provide a novel organic amine sah of monteluakst like n-butylamine, isobutylamine and sec'hntyl amine. • Provide a process for the preparation of pure montelukast sodium via novel organic amine salts. • Provides improved quality of montelukast sodium compound of formula-2 via n-butyl amine salt compound of formula-1. • The n-butyl amine salt of montelukast is free flow solid which is easy to handle in further reaction. • Environment friendly and cost-effective process. Brief Description of the Drawings Figure-1: Illustrates the powder X-ray diffraction pattern of n-butyl amine sah of montelukast. Figure-2: Illustrates the IR spectrum of n-butyl amine salt of montelukast. Figure-3: Illustrates the DSC of n-butyl amine salt of montelukast. Figure-4: Illustrates the powder X-ray diffraction pattern of amorphous montelukast sodium. Detailed description of the present Invention Accordingly the first aspect of the present invention is to provide a novel organic amine salts like n-butyl amine, isobutyl amine and (+/-)-5'^c-butyl amine of montelukast, which can be easily isolated from the reaction mixture in crystalline form, and then, if necessary, purified by recrystallisation from typical organic solvents to reduce the impurities dovm to pharmaceutically acceptable level. The novel organic amine salt of montelukast is easily converted into pure montelukast and/or its pharmaceutically acceptable salts, for example sodium salt. The n-butyl amine salt of montelukast is characterized by X-ray powder diffraction pattern having peaks at about 6.2, 8.6, 8.9, 15.0, 16.9, 18.9, 20.7, 22.6, 25.5 and 29.9 degrees two-theta ± 0.2 degrees two-theta The n-butyl amine salt of montelukast is characterized by X-ray powder diffraction pattern substantially as shown in figure-1. The n-butyl amine salt of montelukast is characterized by IR spectrum as shown in figure-2. The n-butyl amine salt of montelukast is characterized by DSC diagram shown in figure-3. The second aspect of the present invention is to provide a process for the preparation of novel organic amine salt of montelukast compound of formula-1 rurinuia-i which comprises of the follow^ing steps; a) Reacting the diol compound of formula-3 t^ormula-3 with methane sulphonyl chloride in a suitable organic solvent like toluene and acetonitrile or mixtures thereof preferably toluene and acetonitrile in a suitable amine base like diisopropylethylamine to give the compound of formula-4, Formula-4 which in-situ reacting with l-(mercaptomethyl) cyclopropane methyl ester compound of formula-5 Formula-5 in presence of polar aprotic solvent like dimethylsulfoxide, dimethyl acetamide with or without combination of Ci-C4 alcoholic solvents like methanol, ethanol, propanol, butanol, and strong base like alkali or alkaline earth metal alkoxides i.e,. potassium tertiary butoxide, sodium methoxide, sodium ethoxide, preferably sodium methoxide in DMSO (dimethylsulfoxide) at a temperature of-20 to 0°C for 5 to 20 hours, preferably at a temperature of about -5 to S^'C for 8-10 hours, b) Quenching the reaction mixture with an aqueous sodium hydroxide solution, then extracting with water immiscible solvents like hydrocarbon solvents, chloro solvents, ester solvents, preferably hydrocarbon solvents more preferably toluene, c) Lowering pH of the reaction mixture with acetic acid then extracting the montelukast wdth ester solvents, chloro solvents, preferably ester solvents more preferably ethyl acetate followed by concentrating the solvent then dissolving the obtained residue in a suitable solvent selected from keto solvents like acetone, butanone or ester solvents like ethyl acetate, propyl acetate, preferably acetone and ethyl acetate, d) Treating the product obtained from step c. with suitable organic amine such as n-butyl amine, isobutyl amine (+/-)-5^c-butyl amine, preferably n-butyl amine in a suitable solvent selected from non-polar organic solvents like toluene, cyclohexane, hexne, heptane and/or keto solvents like acetone, butanone, methyl isobutyl ketone and/or ester solvents like ethyl acetate, propyl acetate, preferably non-polar organic solvents more preferably toluene followed by seeding with corresponding organic amine salt of montelukast compound, at a temperature of 20-40°C for 5-15 hours, preferably at a temperature of about 25-35°C for 8-10 hours under inert atmosphere to give montelukast n-butyl amine salt compound of formula-1, A^ J^.-^^ /x. A i=\ /\ .-^ ^^ HO-/ H3C CH3 A^ J^.-^^ /x. A. i=\ /\ .-^ ^^ HO-/ H3C CH3 Formula-1 e) Optionally purifying the montelukast n-butyl amine saU compound of formula-1 using hydrocarbon solvents like toluene, hexanes, heptane or keto solvents like acetone or mixture of them. The third aspect of the present invention is to provide a process for the preparation of pure montelukast and/or its pharmaceutically acceptable salt for example sodium salt compound of formula-2 in amorphous form, from novel organic amine salt of montelukast comprises of a) Treating the organic amine salt of montelukast compoxmd of formula-1 with sodium ion source like sodium hydroxide, sodium methoxide preferably sodium hydroxide in methanol at a temperature of 0-40°C for 15 to 90 minutes, preferably at a temperature of 5-15°C for 45 minutes under inert atmosphere, followed by distillation of methanol and the by product of organic amine to get the sodium salt of montelukast, which is then dissolved in a suitable solvent like toluene and saturated the toluene layer with a solvent selected from cyclohexane, hexane, heptane preferably heptane gives montelukast sodium compound of formula-2. Montelukast sodium packed firstly in a primary packing in a clear low-density bag under nitrogen atomosphere tied with a thread or plastic strip, and this bag is placed inside a black colour low-density polyethylene bage and this black colour bag is tied with a thread or plastic strip. This double polythene bag is placed inside a triple laminated bag alaong with silica gel bag and then this triple laminated bag is sealed and kept inside a 30 litres blue coloure HDPE container with a lid and this outer container is sealed. HPLC analysis of montelukast sodium is carried out using symmetry column CI 8, 150 x 3.9 mm ID, 5|i, or equivalent, at a wavelength of 225 nm with gradient flow rate, at 40°C temperature, load is 20 jil, runtime is 40 minutes, RT of the main peak is at about 16 minutes, the diluent is a mixture of sodiumdihydrogen phosphate (3.9 grams of sodiumdihydrogen phosphate in 1000 ml of water) and acetonitrile in the ratio of 37:63 and using dilute ortho phosphoric acid as a buffer. XRD analysis of n-butyl amine salt of montelxxkast is carried out using SIEMENS/D-5000 X-Ray Diffractometer using Cu, Ka radiation of wavelength 1.54 A° and continuous scan speed of 0.045°/min. FI-IR spectrum of n-butyl amine salt of montelukast was recorded on Thermo model Nicolet-380 as KBr pellet. The thermal analysis of n-butyl amine salt of montelukast was carried out on Waters DSC Q-10 model differential scanning calorimeter. The processes described in the present invention were demonstrated in examples illustrated below. These examples are provided as illustration only and therefore should not be construed as limitation of the scope of the invention. Examples: Reference Example-1: A mixture of 8 grams of [(E)]-2-[3(S)-[3-[2-(7-chloro.2-quinolinyl)ethenyl)phenyl]-3-hydroxypropyl]phenyl]"2-propanol, 16 ml toluene and 71.5 ml acetonitrile is heated to 40-50°C. Stirred the reaction mixture for 30 minutes at 40-50°C. Cooled the reaction mixture to -20 to -15°C. Added 2.74 grams of diisopropylethylamine slowly to the above reaction mixture at -20 to -15°C. Stirred the reaction mixture for 45 minutes at -20 to -15°C. Added 2.2 grams of methanesulfonylchloride to the above reaction mixture at -20 to -15°C. Stirred the reaction mixture for 10 hours at -20 to -15°C. Filtered the precipitated solid and washed with chilled acetonitrile followed by hexanes to get the wet solid material. Added 3.12 grams of l-(mercapto methyl) cyclopropane methyl ester to the pre cooled mixture of 32 ml of dimethyl sulfoxide and 14.2 ml of sodium methoxide solution at -5 to 0°C. Stirred the reaction mixture for one hour at -5 to 0°C. The above obtained wet solid material added lot wise to the reaction mixture at -5 to 0°C. Stirred the reaction mixture for 10 hours at -5 to 0°C. Added the above reaction mixture to the pre cooled 238 ml of water at belowlO°C. Stirred the reaction mixture for 30 minutes. Added 32 ml of toluene to the above reaction mixture at 25-30°C. Adjusted the pH of the reaction mixture to 13.4 with aqueous sodium hydroxide (6.3 grams in 238 ml of water) solution. Stirred the reaction mixture for 30 minutes at 25-30'C. Separated the organic and aqueous phases. Washed the aqueous phase thrice with toluene. Then cooled the aqueous phase to 10-20°C. Adjusted the pH of the reaction mixture to 6.6 with aqueous acetic acid solution. Extracted the reaction mixture thrice with ethyl acetate. Washed the organic phase with aqueous sodium bicarbonate solution. Separated the organic and aqueous phases. Dried the organic phase with sodium sulphate. Distilled the solvent completely xmder reduced pressure at below 60°C. Cooled the reaction mixture to 25-30°C. Added 32 ml of toluene to the above reaction mixture. Again distilled the solvent completely under reduced pressure at below 60°C. Reference ExampIe-2: A mixture of 8 grams of [(E)]-2-[3(S)-[3-[2-(7-chloro-2-quinolinyl)ethenyl)phenyl]-3-hydroxypropyI]phenyl]-2-propanol, 16 ml toluene and 71.5 ml acetonitrile is heated to 40-50°C. Stirred the reaction mixture for 30 minutes at 40-50°C. Cooled the reaction mixture to -20 to -15°C. Added 2.74 grams of diisopropylethylamine slowly to the above reaction mixture at -20 to -15°C. Stirred the reaction mixture for 45 minutes at -20 to -15°C. Added 2.2 grams of methanesulfonylchloride to the above reaction mixture at -20 to -15°C. Stirred the reaction mixture for 10 hours at -20 to -15°C. Filtered the precipitated solid and washed with chilled acetonitrile followed by hexanes to get the wet solid material. Added 3.12 grams of l-(mercapto methyl) cyclopropane acetic acid to the pre cooled mixture of 32 ml of dimethyl sulfoxide and 14.2 ml of sodium methoxide solution at -5 to 0°C. Stirred the reaction mixture for 10 hour at -5 to 0°C. Stirred the reaction mixture at -5 to S'^C for 10 hours. Added the reaction mixture to 238 ml of chilled water at below 10°C. Stirred the reaction mixture at 10-20°C for 30 minutes. Slowly added sodium hydroxide solution at 10-20°C. Washed the reaction mixture with toluene and removed the toluene layer. Cooled the aqueous layer to 10-20°C and slowly added 50% acetic acid solution. Extracted the reaction mixture thrice with ethyl acetate. Washed the organic phase with aqueous sodium bicarbonate solution. Separated the organic and aqueous phases. Dried the organic phase with sodium sulphate. Distilled the solvent completely under reduced pressure at below 60°C. Cooled the reaction mixture to 25-30°C. Added 32 ml of toluene to the above reaction mixture. Again distilled the solvent completely under reduced pressure at below 60°C. Example-3: Preparation of montelukast n-butyl amine salt compound of formula-1: Added 48 ml of ethyl acetate to the crude obtained as per the reference example 1 or example-2, followed by 0.9 grams, of n-butyl amine at 25-30°C. Seeded with n-butyl amine sah of montelukast. Stirred the reaction mixture for 8 hours at 25-30°C, Filtered the precipitated solid and washed with ethyl acetate. Dried the material at 60-65°C for 8 hours. Added 32 ml of toluene to the above obtained dried material and heated to 70-80°C. Stirred the reaction mixture for 30 minutes at 70-80°C. Cooled the reaction mixture to 25-35*^C. Stirred the reaction mixture for 10 hours at 25-35°C. Filtered the precipitated solid. Dissolved the wet solid in 79 ml of toluene. Heated the reaction mixture to 70-80°C and stirred the reaction for 30 minutes. Cooled the reaction mixture to 25-30°C. Stirred the reaction for 10 hours at 25-30°C.Filtered the precipitated solid and dried the material at 50-55°C to get the title compound. Yield: 5.7 grams. HPLC Purity: 99.72% Example-4: Preparation of montelukast isobutyl amine salt compound of formula-1 Added 48 ml of ethyl acetate to the crude obtained as per the reference example 1 or example-2, followed by 0.9 grams of isobutyl amine at 25-30°C. Seeded with isobutyl amine salt of montelukast. Stirred the reaction mixture for 8 hours at 25-30°C. Filtered the precipitated solid and washed with ethyl acetate. Dried the material at 60-65°C for 8 hours. Added 32 ml of toluene to the above obtained dried material and heated to 70-80°C. Stirred the reaction mixture for 30 minutes at 70-80°C. Cooled the reaction mixture to 25-35°C. Stirred the reaction mixture for 10 hours at 25-35°C. Filtered the precipitated solid. Dissolved the wet solid in 79 ml of toluene. Heated the reaction mixture to 70-80°C and stirred the reaction for 30 minutes. Cooled the reaction mixture to 25-30°C. Stirred the reaction for 10 hours at 25-30°C.Filtered the precipitated solid and dried the material at 50-55°C to get the title compound. Yield: 5.5 Kgs. HPLC Purity: 99.57% Example-5: Preparation of montelukast (+) sec-butyl amine salt compound of formula-1 Added 48 ml of ethyl acetate to the crude obtained as per the reference example 1 or example-2, followed by 0.9 grams of (+) ^ec-butyl amine at 25-30°C. Seeded with (+)-sec'hntyl amine sah of montelukast. Stirred the reaction mixture for 8 hours at 25-30°C. Filtered the precipitated solid and washed with ethyl acetate. Dried the material at 60-65°C for 8 hours. Added 32 ml of toluene to the above obtained dried material and heated to 70-80°C. Stirred the reaction mixture for 30 minutes at 70-80°C. Cooled the reaction mixture to 25-35°C, Stirred the reaction mixture for 10 hours at 25-35°C. Filtered the precipitated solid. Dissolved the wet solid in 79 ml of toluene. Heated the reaction mixture to 70-80°C and stirred the reaction for 30 minutes. Cooled the reaction mixture to 25-30°C. Stirred the reaction for 10 hours at 25"30°C.Filtered the precipitated solid and dried the material at 50-55°C to get the pure title compound. Yield: 5.2 Kgs. HPLC Purity: 99.27% Example-6: Preparation of montelukast sodium compound of formula-2 Added methanolic sodium hydroxide solution (0.34 grams in 8.5 ml of methanol) to a pre cooled solution of 5.5 grams montelukast n-butyl amine compound of formula-1, 16.5 ml of methanol at 5-10°C. Stirred the reaction mixture for 30 minutes at 5-10°C. Distilled the solvent completely under reduced pressure at 55°C. Cooled the reaction mixture to 35-40°C. Added 11 ml of toluene to the above mass and distilled the solvent completely under reduced pressure at below 65°C. The distillation process repeated twice. Cooled the reaction mixture to 25-30°C. Added 33 ml of toluene to the above reaction mixture. Stirred the reaction mixture for 30 minutes. Treated the reaction mixture with 1.65 grams, of activated carbon. Stirred the reaction mixture for 20 minutes at 25-30°C. Filtered the reaction mixture through hyflow and washed with toluene. Partially distilled the filtrate under reduced pressure at below 65°C. Cooled the reaction mixture to 35-40°C. The above reaction mixture slowly added to 49.5 grams of heptane at 25-30°C. Stirred the reaction mixture for 4 hours at 25-30°C. Filtered the precipitated solid. The obtained wet material taken into RCVD (Roto Cone Vccum Drier) and added 2.1 ml. of methanol, applied vaccum to the RCVD at below 40°C and dried for 4 hours. Temperature of the RCVD raised to 40-50°C and dried for 6 hours under reduced pressure and further raised the temperature to 55-65°C and dried for 8 hours. Unloaded the solid to get pure title compound of formula-2. Yield: 4.4 Kgs. HPLC: 99.72% Particle size : D (v.O.l) is 3.19 ^im, D (v,0.5) is 20.10 ^im, D (v,0.9) is 68.26 ^m, D [4,3] is 29.24 ^im Example-7: Preparation of montelukast sodium compound of formula-2 Added methanolic sodium hydroxide solution (0.34 grams in 8.5 ml of methanol) to a pre cooled solution of 5.5 grams montelukast isobutyl amine compound of formula- 1, 16.5 ml of methanol at 5-10°C. Stirred the reaction mixture for 30 minutes at 5- 10°C. Distilled the solvent completely under reduced pressure at 55°C. Cooled the reaction mixture to 35-40°C. Added 11 ml of toluene to the above mass and distilled the solvent completely under reduced pressure at below 65°C. The distillation process repeated twice. Cooled the reaction mixture to 25-30°C. Added 33 ml of toluene to the above reaction mixture. Stirred the reaction mixture for 30 minutes. Treated the reaction mixture with 1.65 grams, of activated carbon. Stirred the reaction mixture for 20 minutes at 25-30°C. Filtered the reaction mixture through hyflow and washed with toluene. Partially distilled the filtrate under reduced pressure at below 65°C. Cooled the reaction mixture to 35-40°C. The above reaction mixture slowly added to 49.5 grams of heptane at 25-30°C. Stirred the reaction mixture for 4 hours at 25-30°C. Filtered the precipitated solid. The obtained wet material taken into RCVD (Roto Cone Vccum Drier) and added 2.1 ml. of methanol, applied vaccum to the RCVD at below 40°C and dried for 4 hours. Temperature of the RCVD raised to 40-50°C and dried for 6 hours under reduced pressure and further raised the temperature to 55-65°C and dried for 8 hours. Unloaded the solid to get pure title compoimd of formula-2. Yield: 4.2 Kgs. HPLC: 99.48% Example-8: Preparation of montelukast sodium compound of formula-2 Added methanolic sodium hydroxide solution (0.34 grams in 8.5 ml of methanol) to a pre cooled solution of 5.5 grams montelukast (+) sec-butyl amine compound of formula-1, 16.5 ml of methanol at 5-10°C. Stirred the reaction mixture for 30 minutes at 5-10°C. Distilled the solvent completely under reduced pressure at 55°C. Cooled the reaction mixture to 35-40^C. Added 11 ml of toluene to the above mass and distilled the solvent completely under reduced pressure at below 65°C. The distillation process repeated twice. Cooled the reaction mixture to 25-30°C. Added 33 ml of toluene to the above reaction mixture. Stirred the reaction mixture for 30 minutes. Treated the reaction mixture with 1.65 grams, of activated carbon. Stirred the reaction mixture for 20 minutes at 25-30°C. Filtered the reaction mixture through hyflow and washed with toluene. Partially distilled the filtrate under reduced pressure at below 65°C. Cooled the reaction mixture to 35-40°C. The above reaction mixture slowly added to 49.5 grams of heptane at 25-30°C. Stirred the reaction mixture for 4 hours at 25-30°C. Filtered the precipitated solid. The obtained wet material taken into RCVD (Roto Cone Vccum Drier) and added 2.1 ml. of methanol, applied vaccum to the RCVD at below 40°C and dried for 4 hours. Temperature of the RCVD raised to 40-50°C and dried for 6 hours under reduced pressure and further raised the temperature to 55-65°C and dried for 8 hours. Unloaded the solid to get pure title compound of formula-2. Yield: 4.1 Kgs. HPLC: 99.30% We Claim: 1. Montelukast n-butyl amine compound having the fomiula in a crystalline solid forai 2. The n-butyl amine salt compound of montelukast according to claim 1 is characterized by X-ray powder diffraction pattern having peaks at about 6.2, 8.6, 8.9, 15.0,16.9, 18.9,20,7,22.6,25.5 and 29.9 degrees two-theta± 0.2 degrees two-theta. 3. The n-butyl amine salt compound of montelukast according to claim 1 is having X-ray powder diffraction pattern substantially as shown in figure-1, Infrared absorption spectrum substantially as shown in figure-2 and having DSC substantially as shown in figure-3. 4. Montelukast isobutyl amine compound having the formula 5. Montelukast (-^/-ysec-hutyl amine compound having the formula 6. Process for the preparation of novel organic amine salt of montelukast compound of formula-1 comprises of the following steps a. Reacting the diol compound of formula-3 Fonnula-3 with methane sulphonyl chloride in a suitable organic solvent like toluene and acetonitrile or mixtures thereof preferably toluene and acetonitrile in a suitable amine base like diisopropylethylamine to give the compound of formula-4, Fonnula-4 Which in-situ reacting with l-(mercaptomethyl) cyclopropane methyl ester compound of formula-5 in presence of polar aprotic solvent like dimethyl sulfoxide, dimethyl acetamide with or without combination of C1-C4 alcoholic solvents like methanol, ethanol, propanol, butanol, and strong base like alkali or alkaline earth metal alkoxides i.e,. potassium tertiary butoxide, sodium methoxide, sodium ethoxide, preferably sodium methoxide in DMSO (dimethylsulfoxide) at a temperature of -20 to 0°C for 5 to 20 hours, preferably at a temperature of about -5 to 5°C for 8-10 hours, b. Quenching the reaction mixture with an aqueous sodium hydroxide solution, then extracting with water immiscible solvents like hydrocarbon solvents, chloro solvents, ester solvents, preferably hydrocarbon solvents more preferably toluene, c. Lowering pH of the reaction mixture with acetic acid then extracting the Montelukast with ester solvents, chloro solvents, preferably ester solvents more preferably ethyl acetate. Concentrating the solvent then dissolving the obtained residue with a suitable solvent selected from keto solvents like acetone, butanone or ester solvents like ethyl acetate, propyl acetate, preferably acetone and ethyl acetate, d. Treating the product obtained from step c. with suitable organic amine such as n-butyl amine, isobutyl amine and ^ec-butyl amine in a suitable solvent selected from non-polar organic solvents like toluene, cyclohexane, hexane, heptane and/or keto solvents like acetone, butanone, methyl isobutyl ketone or ester solvents like ethyl acetate, propyl acetate, preferably non-polar organic solvents, more preferably toluene followed by seeding with corresponding organic amine salt of montelukast compound, at a temperature of 20-40°C for 5-15 hours, preferably at a temperature of about 25-35°C for 8-10 hours under inert atmosphere, e. Isolating the organic amine salt of montelukast compound of formula-1 from the reaction mixture, f Optionally purifying the montelukast organic amine salt compound of formula-1 using hydrocarbon solvents like toluene, hexanes, heptane and/or keto solvents like acetone or mixture of them. 7. Novel organic amine salt of montelukast such as n-butyl amine, isobutyl amine and (+/-)-5ec-butyl amine used for the preparation of highly pure montelukast and/or its pharmaceutically acceptable salts, 8. n-butyl amine salt of montelukast used for the preparation of highly pure montelukast sodium salt. 9. Process for the preparation of pure montelukast sodium compound of formula-2 from novel organic amine compound of formula-1 comprise of the following. Formula- 1 b) with sodium ion source like sodium hydroxide, sodium methoxide preferably sodium hydroxide in methanol at a temperature of 0-40°C for 15 to 90 minutes, preferably at a temperature of 5-15°C for 45 minutes under inert atmosphere, followed by distillation of methanol and the by product of organic amine to get the sodium salt of montelukast, which is then dissolved in a suitable solvent like toluene and saturated the toluene layer with a solvent selected from cyclohexane, hexane, heptane preferably heptane gives montelukast sodium compound of formula-2. Formula-2 10. The process according to claim 9, wherein the obtained montelukast sodium is in amorphous form.

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