DESC:FIELD OF INVENTION
The present invention provides an industrially feasible process for the preparation of high pure Lasmiditan and its pharmaceutically acceptable salts thereof.

Formula-I

BACKGROUND OF THE INVENTION
Lasmiditan a member of the novel class “ditans”, a serotonin (5-HT)1F receptor agonist, has been approved for the treatment of adult patients suffering from acute migraine with or without aura.The chemical name of Lasmiditan is 2,4,6-Trifluoro-N-[6-(1-methylpiperidin-4-ylcarbonyl)pyridin-2-yl]benzamide. The molecular structure of Lasmiditanis represented by Formula I.

Formula-I
Lasmiditan hemisuccinate, a compound of formula IA marketed as Reyvow® is a tablet available in multiple strengths for oral administration for the acute treatment of migraine with or without aura.

Formula-1A

Lasmiditan and its pharmaceutically acceptable acid addition salts are disclosed in US 7423050 (herein after US’050) and US8697876 (herein after US’876) the patent US’050& US’876 discloses a process for the preparation of Lasmiditan and its salts.

The process for preparation of Lasmiditan and its pharmaceutically acceptable acid addition salts as per US’050is depicted in the following scheme-1& scheme-2

Scheme-1

Scheme-2
The process for preparation of Lasmiditan and its pharmaceutically acceptable salt in particular hemisuccinate as per US’876 is depicted in the following scheme-3.

Scheme-3
Apart from above publications, some of other reported process of Lasmiditan and its intermediates process is elaborated in several patent publications, e.g. CN 110386918, CN 111943930, CN 113045540, WO2018010345, WO 2020095171, WO 2021007155, WO2021001350, WO 2021152462, WO 2021116979, IN201821029969, IN 201911032679, IN 201911029132, IN 201911015218, IN 201911027190&IN 201941034052.

The main draw backs that are evident from prior art process includes but not limited to use of excess copper catalyst and its subsequent removal, use of expensive palladium catalyst for Buchwald coupling with benzophenone imine and subsequent removal of palladium and use of expensive Weinreb amide.

Although there are several processes known in the prior art, still there is a need to develop an alternative effective process to manufacture Lasmiditan and its intermediates on large scale in cost effective manner.

The present invention mainly focused on the draw backs of prior art and focused to develop an industrial feasible eco-friendly process.

OBJECT OF THE INVENTION:
The main object of the present invention is to provide a process for the preparation of high pure Lasmiditan and its pharmaceutically acceptable salts thereof.

Another object of the present invention is to limit the use of excess copper catalyst for the preparation of Lasmiditan intermediates for the preparation of Lasmiditan salts thereof.

Another object of the present invention is feasible large scaleprocess for the preparation of formula III from formula II (piperidine-4-carboxylic acid to piperidine carboxylate) under phase transfer condition to get consistent yield with complete conversion of reactioneven at room temperature.

Yet another object of the present invention is to provide a high pure Lasmiditan hemisuccinate without isolation of Lasmiditan free base.

Yet another object of the invention is, use of novel intermediate salt i.e. des methyl Lasmiditan TFA, for the preparation of pure Lasmiditan hemisuccinate.

Yet another important object of the present invention is to provide a high pure Lasmiditan, using novel salt of Lasmiditan such as 4- hydroxy benzoic acid as an intermediate.

SUMMARY OF THE INVENTION
The present invention is to provide a process for Lasmiditan a compound of formula I, or pharmaceutically acceptable salts thereof,

Formula I
the process comprising:
a) converting compound of Formula II or salt thereof, to compound of Formula III without converting to acid halides, and under phase transfer condition.

b) treating compound of formula-III with formula-IV in presence of suitable reagent and solvent to give compound of formula-V,

c) amination of compound of formula-V to give to compound of formula-VI, in absence of Cu2O

d) treating compound of formula-VI with 2,4,6-trifluorobenzoyl halideto give formula –VII.

e) compound of formula-VII converted to des N-methyl Lasmiditan of formula VIII by treatment with trifluoro acetic acid and isolated as TFA salt.

f) methylation of salt of formula-VIII, followed by saltification in suitable solvent with 4-hydroxybenzoic acid to give Lasmiditan 4-hydroxybenzoate of formula-IX.

g) Lasmiditan 4-hydroxybenzoate of formula-IX converted to Lasmiditan hemisuccinate of formula-IA

BRIEF DESCRIPTION OF THE DRAWINGS
Figure-1 is a characteristic XRPD diagram of Lasmiditan hemisuccinate.
Figure-2 is a characteristic XRPD diagram of Lasmiditan 4-hydroxybenzoate

DETAILED DESCRIPTION OF THE INVENTION
The first aspect of the present invention provides an improved process for the preparation of 2,4,6-trifluoro-N-[6-(1-methylpiperidine-4-carbonyl) pyridine-2-yl]benzamide hemisuccinate comprising following steps;
a) converting Formula II or salt thereof, to Formula III without converting to acid halides, under phase transfer catalyst in presence of coupling agent,suitable base and solvent at preferable temperature.
b) treating compound of formula-III with 2,6 dihalopyridine in presence of appropriate reaction base and solvent at preferable temperature to give formula-V.
c) amination of compound of formula-V to give compound of formula-VI, in presence of base and catalyst.
d) treating formula-VI with 2,4,6-trifluorobenzoyl halide in presence of base and solvent to give formula –VII.
e) compound of formula-VII converted to des N-methyl Lasmiditan TFA salt of formula VIII by treatment with trifluoro acetic acid.
f)methylation of salt of formula-VIII, followed by saltification in suitable solvent with 4-hydroxybenzoic acid to give Lasmiditan4-hydroxybenzoate of formula-IX.
g) Lasmiditan 4-hydroxybenzoate of formula-IX converted to Lasmiditan hemisuccinate of formula-IA.

The process of the present invention can be represented schematically as follows

Wherein

R1, R2 is independently selected from the group selected from hydrogen, alkyl (C1 –C4), alkoxy. Further R1, R2 together form (un)substituted cyclic ring optionally comprising one or more heteroatoms.
R3 is selected from nitrogen protecting group; but not hydrogen.
X is halogen.

The second aspect of the invention provides an eco-friendly process or the preparation of formula III from formula-II or salts thereof under phase transfer catalyst in presence of suitable base and solvent at preferable temperature.

The third aspect of the invention is to provide a high pure Lasmiditan hemisuccinate from Lasmiditan 4-hydroxybenzoate without isolation of Lasmiditan free base.

The forth aspect of the invention is to isolate des-methyl Lasmiditan as a trifluoroacetic acid salt, is a key intermediate for the preparation of high pure Lasmiditan hemisuccinate.

In stage-a, suitable solvent is selected from “ester solvents” such as ethyl acetate, methyl acetate, n-butyl acetate, isobutyl acetate, sec-butyl acetate, isopropyl acetate and the like, “ether solvents” such as tetrahydrofuran, diethyl ether, methyltert-butyl ether, dioxane and the like; “hydrocarbon solvents” such as toluene, xylene, cyclohexane, hexane, heptane, n-pentane, petroleum ether and the like; “chloro solvents” such as dichloromethane, ethylene dichloride, carbon tetrachloride, chloroform., more preferably dichloromethane.

In stage-a, suitable coupling agent is selected from EDCI, HOBt, CDI, DCC, T3P,EEDQ.,more preferably CDI.

In stage-a, suitable phase transfer catalyst is selected from TBAB, TBAI, Tetrabutyl ammonium sulfate, TBAC, Tetra phenylphosphoniumbromide., more preferably TBAB.

In stage-b, suitable solvent is selected from MTBE, DIPE, diethyl ether, dibutyl ether, di phenyl ether, THF, 2-Me THF,2,2,5,5-tetramethyltetrahydrofuran,CPME, 1,4- dioxane, Dimethoxyethane, Dimethoxymethane., more preferably MTBE.

In stage-b, suitable base is selected from n-BuLi, sec-butyl lithium, tert. butyllithium,n-hexyl lithium, LDA, LTMP., more preferably n-BuLi

In stage-c, suitable solvent is selected from isopropyl alcohol, ethylene glycol, glycerol, butyl alcohol, amyl alcohol, propylene glycol, glycerol, cyclohexanol; more preferably isopropyl alcohol.

In stage-c, suitable catalyst is selected from copper (I) bromide,copper (II) bromide, copper iodide, copper (I) chloride,copper (II) chloride, copper (II) sulfate, copper (I)fluoride, copper (II) fluoride, copper (I) hydroxide, copper (II) acetate, copper (II) carbonate, copper (II) nitrate.; more preferably copper iodide.

In stage-c, amine source is selected from aq. ammonia, methanolic ammonia, ammonia gas, ammonium carbonate, ammonium sulfate, ammonium chloride.; more preferably aq. ammonia.

In stage-d, suitable solvent is selected from dichloromethane, toluene, xylenes, THF, 2Me THF, MTBE, CPME (cyclopropyl methyl ether), isopropyl acetate, butyl acetate, ethylacetate, dimethylformamide, acetone, MIBK, acetonitrile, chlorobenzene, cyclohexane, diglyme, DME, DMSO, 1,4- dioxane, NMP, pyridine, 2-picoline, 3-picoline, 4-picoline, triethylamine,trimethylamine N,N-Diisopropyl ethylamine; more preferably dichloromethane.

In stage-d, suitable reagent for acid chloride formation is selected from oxalyl chloride, thionyl chloride, trichloroisocyanuric acid, cyanuric chloride, more preferably oxallyl chloride.

In stage-d, suitable base is selected from pyridine, 2-picoline, 3-picoline, 4-picoline, triethylamine, trimethylamine, piperidine, N-methyl piperidine, N-ethyl piperidine, N,N-Diisopropyl ethylamine, pyrazine, pyridazine, pyrimidine, potassium carbonate, sodium carbonate, sodium hydroxide, potassium hydroxide, calcium hydroxide, barium hydroxide, potassium bicarbonate, sodium bicarbonate, cesium carbonate.; more preferably N,N-Diisopropyl ethylamine.

In stage-e, suitable solvent is selected from dichloromethane, toluene, xylenes, THF, 2Me THF, MTBE, CPME (cyclopropyl methyl ether), isopropyl acetate, butyl acetate, ethylacetate, dimethylformamide, acetone, MIBK, acetonitrile, chlorobenzene, cyclohexane, diglyme, DME, DMSO, 1,4- dioxane.; more preferably dichloromethane.

In stage-e, suitable reagent for Boc deprotection is selected from trifluoroacetic acid, trichloroacetic acid, chloroacetic acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, phosphoric acid, nitric acid, sulfamic acid, potassium hydrogen sulfate, Ferric chloride, Zinc chloride, Indium chloride, potassium tertbutoxide, sodium tertbutoxide, sodium methoxide; more preferably trifluoroacetic acid.

In stage-f, suitable reagent for N-methylation is selected from formic acid- formaldehyde, formaldehyde-sodiumcyanoborohydride, formaldehyde- sodium borohydride, formaldehyde-hydrogen-Pd/C, formaldehyde-ammonium formate- Pd/C, methyliodide, methyltriflate, methylfluorosulfonate, Trimethyloxoniumtetrafluoroborate; more preferably formic acid- formaldehyde.

In stage-f, suitable acid is selected from 4-hydroxybenzoic acid,3-hydroxybenzoic acid, benzoic acid, 2,4- dinitrobenzoicacid,pamoic acid, 1- Naphthoic acid, 2- Naphthoic acid, oxalic acid, citric acid, malonic acid, glutaric acid, adipic acid, maleic acid, fumaric acid, malic acid.; more preferably 4-Hydroxybenzoic acid.

In stage-g, suitablesolvent is selected from acetone, DCM, ethylacetate, butylacetate, isopropylacetate, MIBK, methylethyl ketone, methanol, ethanol, isopropyl alcohol, MTBE; more preferably DCM, isopropylacetate and acetone.

The following examples illustrate the nature of the invention and are provided for illustrative purposes only and should not be construed to limit the scope of the invention.

Example-1:Preparation of 1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid(Formula-II):
To a stirring solution of isonipecotic acid (100 g) in water (1000 mL), sodium carbonate (148 g) and BOC anhydride (186 g) was added. The resulting mixture was stirred at 30°C. After completion of reaction, adjust the mixture pH to 2±0.5 with 50 % aq. HCl at 20 to 30°C. Filter the solid and dry the product until the water content is NMT 0.5% w/w. Isolated yield: 162 g (91%) with HPLC purity of 98 %.
Mass spectrum (m/z) = 228.25 (M-H) +
1H NMR (400 MHz; CDCl3): d 4.01-4.03 (d, J=8Hz, 2H), 2.83-2.88 (t, J=11.6Hz, 2H), 2.45-2.53 (m, 1H), 1.89-1.93 (m, 2H), 1.61-1.64 (m, 2H), 1.45 (s, 9H).

Example-2 A: Preparation of tert-butyl 4-(dimethylcarbamoyl)piperidine-1-carboxylate(Formula-III)
To a stirring solution of dichloromethane, 1,1’-Carbonyldiimidazole (85 g), 1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid (100 g)was added and stirred at 30°C.Tetra butyl ammonium bromide (7 g) and N, N’-Dimethylamine HCl (46.2g) were added and stirred at 30°C.The reaction mixture was washed with aqueoushydrochloric acid followed by aqueous sodium carbonate. Dichloromethane was distilled and added n-Heptane. Filtered the solid and dried at 40°Cuntil the water content is NMT 0.5% w/w.
Isolated yield: 100.62 g (90%) with HPLC purity of 98 %.
Mass spectrum (m/z) = 257.18 (M+H)+
1H NMR (400 MHz; CDCl3): d 3.06 (s, 3H), 2.95 (s, 3H), 2.76 (bs, 2H), 2.60-2.68(m, 1H), 1.68-1.72 (m, 6H), 1.46 (s, 9H).

Example-2B: Preparation of tert-butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate(formula-III)
To a stirring solution of dichloromethane, add1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid (100 g), 1, 1’-Carbonyldiimidazole (84.87g) at about 10°C followed bytetra butyl ammonium bromide (7.03 g) andN,O-Dimethylhydroxylaminehydrochloride (51.05 g) in water at about 10°C. After reaction completion, reaction mixture was washed with aqueoushydrochloric acid followed by aqueous sodium carbonate. Dichloromethanewas distilled and addedn-Heptane. Thesolid was filtered and dried at 40°C until the water content is NMT 0.5% w/w.
Isolated yield: 113.5 g (95.5%) with HPLC purity of 98%.
Mass spectrum (m/z) = 273.18 (M+H)+
1H NMR (400 MHz; CDCl3): d 4.15 (brs, 2H), 3.71 (s, 3H), 3.18 (s, 3H), 2.81-2.77(m, 3H), 1.72-1.65 (m, 4H), 1.46 (s, 9H).

Example-3: Preparation of tert-butyl 4-(6-bromopicolinoyl) piperidine-1-carboxylate(formula-V)
To the stirring solutionof MTBEand2,6-Dibromopyridine (154.3 g) was added 2.5Mn-Butyl lithium in hexanes (273 mL) at -80°C to -70°C followed tert-butyl 4-(dimethyl carbamoyl) piperidine-1-carboxylate (100 g) asMTBEsolutionat -80°C to -70°C. The reaction wasquenched with aqueous ammonium chloride.Organic layer waswashedwith aqueous sodium chloride solution.MTBE was distilled and n-heptaneadded. The solidwas filtered and driedat 45°C.
Isolated yield: 101 g (70%)
Mass spectrum (m/z) = 269.02 (M - Boc)+
1H NMR (400 MHz; CDCl3): d 7.99-7.97 (dd, J=7.3, 1.2 Hz, 1H), 7.73-7.69 (m, 1H), 7.67-7.66 (dd, J=7.9, 1.2 Hz, 1H), 4.16 (s, 2H), 3.97-3.90 (tt, J=11.4, 3.6 Hz, 1H), 2.96-2.90 (t, J=12.0 Hz, 2H), 1.90-1.87 (d, J=12.5 Hz, 2H), 1.67-1.63 (dd, J=11.9, 4.1 Hz, 2H), 1.47 (s, 9H).

Example-4: Preparation of tert-butyl 4-(6-aminopicolinoyl) piperidine-1-carboxylate(formula-VI)
To the stirring solution of isopropanol, copper (I) iodide (0.516 g), tert-butyl 4-(6-bromopicolinoyl) piperidine-1-carboxylate (100g) was added followed by aqueous ammonia (700 mL).The reaction mixture washeated at about 90°C in an autoclave. The product was extracted intoMTBE and washed with aq. oxalic acid. The aq.oxalic acid layer was treated with aq.sodium hydroxide and product extracted into MTBE. MTBEwas distilled and the product was isolated by addition of n-heptane. The product was dried at45°C.
Isolated yield: 58g (70%)
Mass spectrum (m/z) = 306.17 (M +H)+
1H NMR (400 MHz; CDCl3): d 7.60-7.50 (m, 1H), 7.38 (dd, J=7.4, 0.7 Hz, 1H), 6.67 (dd, J=8.2, 0.7 Hz, 1H), 4.54 (s, 2H), 4.14 (s, 2H), 3.89 (tt, J=11.4, 3.6 Hz, 1H), 2.89 (t, J=11.4 Hz, 2H), 1.85 (s, 2H), 1.60 (dd,J=22.1, 9.4 Hz, 2H), 1.46 (s, 9H).

Example-5: Preparation of tert-butyl 4-(6-(2,4,6-trifluorobenzamido)picolinoyl)piperidine-1-carboxylate(formula-VII)
To the stirring solution ofdichloromethane,2,4,6-trifluorobenzoic acid (75g), Dimethylformamide (1.27 mL) and oxalyl chloride (66.5 g) was added and stirred at 35-40°C.N,N-diisopropylethylamine (72 g) was added followed by tert-butyl 4-(6-aminopicolinoyl) piperidine-1-carboxylate (100g) in dichloromethane at 0-10°C.Washed the reaction mixture with water followed by aqueous sodium carbonate solutionDichloromethanewas distilled and the product was isolated with n-heptane.The solid was recrystallized using dichloromethane and n-heptane, driedthe product at 40°C.
Isolated yield: 118 g (77 %) with HPLC purity 97%.
Mass spectrum (m/z) = 464.17 (M +H)+
1H NMR (400 MHz; CDCl3): d 8.53 (d, J=8.1 Hz, 1H), 8.48 (s,1H), 7.97-7.90 (m,1H), 7.84 (dd, J=7.6, 0.9 Hz, 1H) 6.86-6.78 (m, 2H), 4.13 (s, 2H), 3.86 (tt, J=11.2, 3.4 Hz, 1H), 2.88 (t, J=11.9 Hz, 2H), 1.85 (d, J=10.7 Hz, 2H), 1.63 (td, J=14.8, 3.4 Hz, 2H), 1.46 (s, 9H).

Example-6:Preparation of 2,4,6-trifluoro-N-(6-(piperidine-4-carbonyl)pyridin-2-yl) benzamidetrifluoroacetate(formula-VII)
To the stirring solution of tert-butyl 4-(6-(2,4,6-trifluorobenzamido)picolinoyl)piperidine-1-carboxylate (200 g) in dichloromethane, trifluoroacetic acid (469 mL) wasaddedat about 10°C and warmed to 30 °C. After completion of reaction, purified water was added. Adjusted the reaction mixture pH to 7.5-8.5 with aqueous sodium carbonate solutionThe product was filtered and purified with n-heptane, dried the product at 50°C.
Isolated yield: 185.4 g (90 %) with HPLC purity 99 %.
Mass spectrum (m/z) = 362.1 (M - H)+
1H NMR (400 MHz; DMSO-d6): d 11.51 (s, 1H), 8.85 (s,1H), 8.56 (s,1H), 8.39 (d, J=7.4 Hz, 1H) 8.10 (t,J=7.9 Hz, 1H), 7.78 (d, J=7.5 Hz, 1H), 7.40 (dd, J=9.2, 8.0 Hz, 2H), 3.92 (s, 1H), 3.35 (s, 2H), 2.99 (t, J=11.8 Hz, 2H), 2.17-1.99 (m, 2H), 1.74 (td, J=14.6, 3.5 Hz, 2H).

Example-7:Preparation of 2,4,6-trifluoro-N-(6-(1-methylpiperidine-4-carbonyl)pyridin-2-yl)benzamide 4-hydroxybenzoate(formula- IX)
To the stirring solution of 2,4,6-trifluoro-N-(6-(piperidine-4-carbonyl)pyridin-2-yl) benzamidetrifluoroacetate (200 g) in formic acid (600 mL),37% formaldehyde (46 mL) was added and stirred at about 90°C. After completion of reaction,water was added at about 30°C. Extracted the reaction mixture with dichloromethane and washed with aqueous sodium hydroxide. Dichloromethanewas distilled and swapped with acetone. 4-hydroxy benzoic acid (61g) was added and stirred at reflux temperature. The product was isolated by filtration. Dried the product at 50°C
Isolated yield: 135 g (62.5 %; over two steps).
Mass spectrum (m/z) = 376.12 (M - H)+
1H NMR (400 MHz; d6-DMSO): d 11.46 (s, 1H), 8.37 (d, J=7.5 Hz, 1H), 8.05 (t, J=7.9 Hz, 1H), 7.79-7.75 (m, 2H) 7.73 (d, J=7.5 Hz, 1H), 7.37 (t, J=8.6 Hz, 2H), 6.85-6.75 (m, 2H), 3.67 (s, 1H), 2.82 (d, J=11.3 Hz, 2H), 2.17 (s, 3H), 1.98 (t, J=11.1 Hz, 2H), 1.79 (d, J=11.4, 2H), 1.55 (dd, J=21.8, 11.1 Hz, 2H). HPLC purity : 99%

Example-8: Preparation of 2,4,6-trifluoro-N-[6-(1-methylpiperidine-4-carbonyl)pyridine-2-yl]benzamide hemisuccinate. (formula -IA)
To the stirring solution of 2,4,6-trifluoro-N-(6-(1-methylpiperidine-4-carbonyl)pyridin-2-yl)benzamide 4-hydroxybenzoate (120 g) in dichloromethane wasaddedaqueous sodium hydroxide solution. The organic layer was separated,distilled and swapped with acetone. Succinic acid (16.5g) was added andstirred at reflux temperature. The product was filtered and dried at 50°C under vacuum.
Isolated yield: 84 g (82.6 %) with 99.8% HPLC purity.
Mass spectrum (m/z) = 376.1 (M - H)+
1H NMR (400 MHz; d6-DMSO): d 11.46 (s, 1H), 8.39-8.38 (d, J=7.2 Hz, 1H), 8.09-8.06 (t, J=8 Hz, 1H), 7.75-7.34 (d, J=7.6 Hz, 1H) 7.42-7.37 (m, 2H), 3.69 (bs, 1H), 2.89-2.87 (d, J=11.2 Hz,2H), 2.36 (s, 2H), 2.24 (s, 3H), 2.10-2.05 (t, J=11.2, 2H), 1.85-1.82 (d, J=10.8 Hz, 2H), 1.62-1.54 (m, 2H).
,CLAIMS:1. A process for preparation of Lasmiditan of formula I, or pharmaceutically acceptable salts thereof, comprising the steps of

Formula I
a) converting Formula II or salt thereof, to Formula III without converting to acid halides,

b) treating compound of formula-III with formula-IV in presence of appropriate base and solvent at preferable temperature to give formula-V

Wherein R1, R2 is independently selected from the group selected from hydrogen, alkyl (C1 –C4), alkoxy (or) R1, R2 together form (un)substituted cyclic ring optionally comprising one or more hetero atoms.
R3 is selected from nitrogen protecting group; but not hydrogen.
X is halogen.

c) amination of compound of formula-V to give to compound of formula-VI, in presence of base and absence of Cu2O

d) treating compound of formula-VI with 2,4,6-trifluorobenzoyl halide in presence of base and solvent to give formula –VII

e) compound of formula-VII converted to des N-methyl Lasmiditan of formula VIII by treatment with trifluoro acetic acid and isolated as TFA salt.

f) methylation of salt of formula-VIII, followed by saltification in suitable solvent with 4-hydroxybenzoic acid to give Lasmiditan 4-hydroxybenzoate of formula-IX.

g) Lasmiditan 4-hydroxybenzoate of formula-IX converted to Lasmiditan hemisuccinate of formula-IA

2. The process according to claim-1, wherein converting Formula II or salt thereof, to Formula III, under phase transfer catalyst in presence of coupling agent, suitable base and solvent in presence of room temperature

3. The process according to claim-1, wherein amination of compound of formula-V to give to compound of formula-VI, in presence of base and catalyst.

4. The process according to claim-1, formula-VIII is used for the preparation of highly pure Lasmiditan hemisuccinate, without isolating Lasmiditan free base.

5. The intermediates of formula-VIII and formula-IX are used for the preparation of Lasmiditan hemisuccinate of formula-1A.

6. The crystalline form of formula-IX according to claim-5, having characteristic peaks at 15.2±0.2?, 16.3±0.2?, 19.2±0.2?

7. The crystalline form of formula-IX according to claim-6, having further characteristic peaks at 22.0±0.2?, 23.5±0.2?, 25.8±0.2?.

8. The process according to claim-1, Lasmiditan 4-hydroxybenzoate of formula-IX converted to Lasmiditan hemisuccinate of formula-IA without isolating Lasmiditan free base of formula-1.

9. The process according to clam-1, Lasmiditan hemisuccinate having XRPD characteristic peaks at 7.6±0.2?, 13.2±0.2?, 15.2±0.2? as per fig-1

10. The process according to claim-9, Lasmiditan hemisuccinate having XRPD characteristic peaks at 16.9±0.2?, 17.3±0.2?, 20.2±0.2?, 23.5±0.2?, 25.3±0.2?.