A PROCESS FOR PREPARATION OF TETRAHYDROCARBAZOLONE DERIVATIVES
Filed of Invention
The present invention provides a process for preparing tetrahydrocarbazolone derivatives, particularly for the preparation of l,2,3,9-tetrahydro-9-methyl-3-[(2-methyl)-1H-imidazol-1-yl) methyl]-4H-carbazol-4-one (Ondansetron). Background and Prior Art
l,2,3,9-tetrahydro-9-methyl-3-[(2-methyl)-1H-imidazol-l-yl)methyl]-4H-carbazol-4-one of Formula-I, which is used as an anti-vomiting agent due to its selective action on 5HT3 receptors and is represented by the structural formula given below:

The compound was first disclosed in UK Patent Application No.GB8501889.3 in 1985 claiming priority of UK Patent Applications GB8401888 filed on 25-01-1984 and GB8425959 filed on 15-10-1984. GB8501889.3 or corresponding US Patent 4695578 discloses many methods for preparation of Ondansetron,
In one process disclosed in US 4695578, Ondansetron is prepared by N-methylation of
l,2,3,9-tetrahydro-3-[(2-methyl-lH-imidazol-l-yl)methyl]-4H-carbazol-4-one of
Formula-II with strong base like sodium hydride and dimethylsulfate in solvents such as dimethylformamide, THF or an aromatic hydrocarbon, such as, toluene, etc.


The disadvantage of this process is the yield of this reaction is low, since the activation of the ring nitrogen atom is difficult and the sodium hydride used as strong base, which is hazardous chemical.
Yet in another process disclosed in US 4695578, Ondansetron is prepared from hydrochloride salt of 3-[(dimethylamino)-methyl]-l,2,3,9-tetrahydro-9-methyl-4H-carbazol-4-one of Formula-Ill by treating it with 2-methylimidazole in a medium of solvent such as water or an alcohol or their mixture thereof at reflux temperatures for longer period of time like 20 to 47 hours as shown in Scheme 1. The yield is poor and the time for completion of reaction is high. Scheme 1

Still yet another process disclosed in US 4695578, preparation of Ondansetron is by Michael-type addition reaction of 2-methylimidazole to 9-methyl-3-methylene"l,2,3,9-tetrahydro-4H-carbazol-4-one of Formula-V which according to this patent is prepared from 3-[(trimethylamino)-methyl]-l,2,3,9-tetrahydro-9-methyl-4H-carbazol-4-one iodide (Formula-IV) as shown in Scheme 2.


This particular reaction is carried out in solvent systems such as water, ethyl acetate, ketone e.g. acetone, MIBK and amides over a period of time of 20 hours resulting in 44% yield. The disadvantage of this process is low yield and using expensive reagent methyl iodide for quatemization.
Still yet another process disclosed in US 4695578 is a substitution of 2-methyl-lH-imidazole for chloride in 3-(chloromethyl)-l,2,3,9-tetrahydro-9-methyl-4H-carbazol-4-one of Formula VI . This reaction was carried out in solvents such as an amide e.g. Dimethyl formamide, an alcohol, e.g. methanol or industrial methylated spirit or a haloalkane e.g. dichloromethane, etc., resulting in about 72% yield.

In another prior art, US 4957609, Ondansetron is prepared by a different route of synthesis given in the Scheme 3, wherein the last step is the closure of the central ring of l,2,3,9-tetrahydrocarbazol-4-one ring system starting with a compound of Formula VII

where X is a hydrogen or a halogen atom using copper or palladium catalyst. The solvent system used for the reactions includes N,N-dimethylformamide (DMF), N-methylpyrrolidone, hexamethylphosphoramide (HMPA), nitriles and alcohols. This process suffers from many disadvantages such as reaction specificity/regio-specificity in amino-methylation reaction and other side reactions and decomposition; accordingly this process is not suitable for industrial preparation of ondansetron. Scheme 3

US 6388091 discloses an improvement for preparing Ondansetron according to Scheme 4, wherein a Silyl enol ether of l,2,3?9-tetrahydro-9-methyl-4H-carbazol-4-one of Formula VIII is alkylated with l-(N,N-dialkylaminomethyl)-2-methylimidazole in presence of an organic solvent such as methylenedichloride, chloroform, acetonitrile, tetrahydrofuran, dioxane, toluene, N,N-dimethylformamide, ethanol or mixture thereof resulting in an yield in the range of 81 to 86%. The process improves the yield of Ondansetron but it lacks industrial applicability. One of the reasons being silyl reagents are costly. Apart from this, the l-(N,N-dialkylaminomethyl)-2-methylimidazole reagent has to be prepared, since it is not a commercially available reagent and therefore increases the number of steps in the process.


The process disclosed in EP 219,929 involves carbazole formation in the last step and is summarized as follows:

In the above reaction, an anhydrous condition is required in order to introduce a dimethylamino group. Further, the process is completed through many steps and employs an expensive reagent like n-butyllithium and tetrahydrofuran. Accordingly, the process disclosed in this patent has difficulties to be applied to an industrial-scale mass production.
Another prior art document, WO 02/055492A2 discloses a process of using 1,2,3,9-tetrahydro-9-methyl-4H-carbazol-4-one as an initial substrate to prepare dimethylamino-methyl carbazolone, which is then converted to Ondansetron. The disadvantages of this process are use of glacial acetic acid, a corrosive solvent, and requirement of 12 hours of heating.
EP 1585744 Bl discloses an improved process for preparing the Ondansetron, wherein the conversion of carbazolone to Ondansetron occurs in the presence of water binding agent and non-aqueous polar solvent. The improvement is due to the presence of water binding agent. Typically water binding agents are organic or inorganic acids such as acetic anhydride, phosphorus pentoxide anhydrate or methane sulfonic acid. Suitable solvents include an amide, a ketone, an ester, an acid or a mixture thereof and preferably the solvent is N,N-dimethylformamide. The reaction generally proceeds under acidic

condition and typically at an elevated temperature in the range of 50°C to 150°C ,
preferably 90°C to 120°C and in some embodiments 100 °C to 110°C .
US 7,098,345 discloses a process for the preparation of ondansetron comprising,
contacting 3-[(dimethylamino)methyl]-l,2,3,9-tetrahydro-9-methyl-4H-carbazol-4-one or
salt thereof and 2-methylimidazole in a solvent system comprising water and N,N-
dimethylformamide, to form 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1 H-imidazol-1 -
yl)methyl]-4H-carbazol-4-one. The reaction mixture is heated to reflux and stirred for
sufficient period of time and then cooled to obtain the precipitated crude ondansetron
base. The precipitated crude ondansetron base was filtered and dried. The major impurity
is the exomethylene carbazolone which amounted to 2.6% of the crude ondansetron base.
Recrystallisation of crude ondansetron yielded pure ondansetron base having 99.6%
HPLC purity with 0.25% contamination by the exomethylene carbazolone.
The main object of the present invention is to provide a process for preparing Ondansetron
in the absence of solvent which is free from exomethylene carbazolone impurity and in
good yield.
Summary of the invention
The present invention provides a process for preparing tetrahydrocarbazolone derivatives
of Formula (A)
wherein Rl represents a hydrogen atom, a C1-10 alkyl, a C3-7 cycloalkyl-(CM) alkyl group, a C3-10 alkynyl group, a phenyl or a phenyl-C1-3 alkyl group; and R2, R3 and R4 each independently represents a hydrogen atom, a C1-6 alkyl, a C3.7 cycloalkyl, a C2-6 alkenyl or a phenyl-(C1-3) alkyl group and at least two groups independently represent a hydrogen atom or a C1-6 alkyl group;

said process comprising of; mixing a compound of Formula (B)

(wherein Rl represents a hydrogen atom, a C1-10 alkyl, a C3.7 cycloalkyl-(C]-4) alkyl group, a C3-10 alkynyl group, a phenyl or a phenyl-C1-3 alkyl group, Y represents a reactive substituent and hydrogen halide is hydrogen fluoride, hydrogen chloride, hydrogen bromide, or hydrogen iodide) or a protected derivative thereof with an imidazole of Formula (C)

(wherein R2, R3 and R4 each independently represents a hydrogen atom, a C1-6 alkyl, a C3-7 cycloalkyl, a C2-6 alkenyl or a phenyl-(C1-3) alkyl group and at least two groups independently represent a hydrogen atom or a C1-6 alkyl group) in the absence of solvent to obtain a corresponding reaction mixture of compound of Formula (B) and compound of Formula (C), melting said reaction mixture at a temperature in the range of 80 to 180°C , stirring the reaction mixture at 85°C for a period of time in the range of 20 minutes to 2 hours, and obtaining tetrahydrocarbazolone derivative by adding water to the reaction mixture and stirring for 1 hour at room temperature followed by cooling the reaction mixture.
Detailed description of the invention
Accordingly, the present invention provides a process for preparing tetrahydrocarbazolone derivatives of Formula (A)

wherein
Rl represents a hydrogen atom, a C1-10 alkyl, a C3.7 cycloalkyl-(C1-4) alkyl group, a
C3-10 alkynyl group, a phenyl or a phenyl-C1-3 alkyl group; and R2, R3 and R4
each independently represents a hydrogen atom, a C1-6 alkyl, a C3.7 cycloalkyl, a
C2-6 alkenyl or a phenyl-(C1-3) alkyl group and at least two groups independently
represent a hydrogen atom or a C 1-6 alkyl group;
said process comprising of;
(a) mixing a compound of Formula (B)

(wherein Rl represents a hydrogen atom, a C1-0 alkyl, a C3.7 cycloalkyl-(C1-4) alkyl group, a C3-10 alkynyl group, a phenyl or a phenyl-C1-3 alkyl group, Y represents a reactive substituent and hydrogen halide is hydrogen fluoride, hydrogen chloride, hydrogen bromide, or hydrogen iodide) or a protected derivative thereof with an imidazole of Formula (C)


Formula (C) (wherein R2, R3 and R4 each independently represents a hydrogen atom, a C1-6 alkyl, a C3-7 cycloalkyl, a C2-6 alkenyl or a phenyl-(C1-3) alkyl group and at least two groups independently represent a hydrogen atom or a C1-6 alkyl group) in the absence of solvent to obtain a corresponding reaction mixture of compound of Formula (B) and compound of Formula (C),
(b) melting said reaction mixture at a temperature in the range of 80 to 180 1.6 ,
(c) stirring the reaction mixture at 85 1.6 for a period of time in the range of 20 minutes to 2 hours, and
(d) obtaining tetrahydrocarbazolone derivative by adding water to the reaction mixture and stirring for 1 hour at room temperature followed by cooling the reaction mixture.
A preferred class of compounds within the scope of general Formula (A) is that wherein
Rl represents a hydrogen atom, a C1-10 alkyl, a C3-7 cycloalkyl, a C3.6 alkenyl, a phenyl or
a phenyl-C1-3 alkyl group, and R2, R3 and R4 each independently represents a hydrogen
atom, a C1.6 alkyl, a C3-7 cycloalkyl, a C2-6 alkenyl or a phenyl-C1-3 alkyl group and at least
two groups independently represent a hydrogen atom or a C1-6 alkyl group;
It will be understood that when Rl represents a C3-6 alkenyl group or a C3-10 alkynyl
group, the double or triple bond may not be adjacent to the nitrogen atom.
Referring to the Formula (A), the alkyl groups represented by Rl, R2, R3 and R4 may be
straight chain or branched chain alkyl groups, for example, methyl, ethyl, propyl, prop-2-
yl, butyl, but-2-yl, 2-methlprop-2-yl, pentyl, pent-3-yl or hexyl.
An alkenyl group may be, for example, a propenyl group.
A phenyl-C1-3 alkyl group may be, for example, a benzyl, phenethyl or 3-phenylpropyl
group.
A cycloalkyl group may be, for example, a cyclopentyl, cyclohexyl or cycloheptyl group.
A C3-7 cycloalkyl-(Ci.4) alkyl group may be for example a cyclopropylmethyl,
cyclopentenylpropyl or a cycloheptylmethyl group. When the cycloalkyl moiety contains
5, 6, or 7 carbon atoms it may optionally contain one or two double bonds, and may be for
example a cyclohexenyl or cyclohexadienyl group.
A C3-10 alkynyl group may be, for example, a 2-propynyl or 2-octynyl group.

A preferred class of compounds represented by the Formula (A) is that wherein Rl represents a hydrogen atom, a C1-6 alkyl, a C3-6 cycloalkyl or a C3-6 alkenyl group. Another preferred class of compounds represented by the Formula (A) is that wherein R2, R3 and R4 each independently represents a C1-3 alkyl, C3-6 cycloalkyl or C3-6 alkenyl group and at least two groups independently represent a hydrogen atom or a C1.3 alkyl group.
A further preferred class of compounds represented by the Formula (A) is that wherein Rl represents a hydrogen atom, a C1.6 alkyl, a C5.6 cycloalkyl or a C3-4 alkenyl group, and either R2 represents a hydrogen atom and R3 and/or R4 represents a C1.3 alkyl group or R2 represents a C1.3 alkyl group and both R3 and R4 represent hydrogen atoms. A particularly preferred class of compounds according to the invention, wherein Rl represents a hydrogen atom, a methyl, ethyl, propyl, prop-2-yl, prop-2-enyl or cyclopentyl group; R3 represents a hydrogen atom; and either R2 represents a methyl, ethyl, propyl or prop-2-yl group and R4 represents a hydrogen atom or R2 represents a hydrogen atom and R4 represents a methyl or ethyl group.
Preferred compounds include: 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-l-
yl)methyl]-4H-carbazol-4-one; l,2,3,9-tetrahydro-3-[(2-methyl-1H-imidazol-l-
yl)methyl]-9-(prop-2-enyl)-4H -carbazol-4-one; 9-cyclopentyl-l,2,3,9-tetrahydro-3-[(2"
methyl-1H-imidazol-l-yl)methyl]-4H-carbazol-4-one; l,2,3,9-tetrahydro-3-[2-methyl-1H-
imidazol-l-yl)methyl]-9-(prop-2-yl)-4H-carbazol-4-one; 9-[(cyclopropyl)methyl]-l,2,3,9-
tetrahydro-3-[(2-methyl-1H-imidazol-l-yl)methyl]-4H-carbazol-4-one; 1,2,3,9-tetrahydro-
3-[(2-methyl-1H-imidazol-l-yl)methyl]-9-(prop-2-ynyl)-4H-carbazol-4-one; 9-
(Cyclobutylmethyl)-l,2,3,9-tetrahydro-3-[(2-methyl-1H-imidazol-l-yl)methyl]-4H-
carbazol-4-one; 9-(Cyclopentylmethyl)-l,2,3,9-tetrahydro-3-[(2-methyl-1H-imidazol-l-
yl)methyl]-4H-carbazol-4-one; l,2,3,9-Tetrahydro-3-[(2-methyl-1H-imidazol-l-
yl)methyl]-9-(2-octynyl)-4H-carbazol-4-one; 9-(3-Cyclopentylpropyl)-l,2,3,9-tetrahydro-3-[(2-methyl-1H-imidazol-l-yl)methyl]-4H-carbazol-4-one; and 9-(Cycloheptylmethyl)-l,2,3,9-tetrahydro-3-[(2-methyl-1H-imidazol-l-yl)methyl]-4H-carbazol-4-one. Preferred compounds of Formula (B) employed as starting materials in the process include compounds wherein Y represents a group selected from a group of formula CH2Z where Z represents a group ~NR5R6 where R5 and R6 which may be the same or different each

represents lower alkyl e.g. methyl, aryl e.g. phenyl or aralkyl e.g. benzyl, or R5 and R6
together with the nitrogen atom to which they are attached may form a 5- to 6-membered
ring e.g. a pyrrolidine ring, for example -N(CH3)2.
The hydrogen halide is selected from a group of hydrogen fluoride, hydrogen chloride,
hydrogen bromide, and hydrogen iodide, preferably hydrogen chloride.
The present invention also provides a process for preparing l,2,3,9-tetrahydro-9-methyl-3-
|(2-methyl-lH-imidazol-l-yl)methyl]-4H-carbazol-4-one of Formula (I)

in the absence of solvent to obtain a corresponding reaction mixture of compound of Formula (D) and Formula (E), (b) melting said reaction mixture at a temperature in the range of 80 to 180oC,

(c) stirring the reaction mixture at 85oC for a period of time ranging from 20 minutes to 2 hours, and
(d) obtaining l,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-lH-imidazol-l-yl)methyl]-4H-carbazol-4-one by adding water to the reaction mixture and stirring for 1 hour at room temperature, followed by cooling the reaction mixture.
The steps of the process are also depicted in the form of the following reaction scheme;

In accordance with the present invention the compound of Formula (E), 2-
methylimidazole is employed in an amount ranging from 1.2 to 3.5 molar equivalents
based on the amount of the compound of Formula (D).
The reaction may be performed at a temperature ranging from 80oC to 1 180oC, preferably
100oC to 115oC for a period of time ranging from 20 minutes to 2 hours.
On completion of the reaction, crude Ondansetron is isolated conveniently from the
reaction medium by adding water to precipitate the product and filtering at room
temperature. The yield and purity of Ondansetron are very high in comparison with earlier
reports.
It is also an embodiment of the present invention wherein the reaction is performed at a
temperature ranging from 80oC to 180oC, preferably 100oC to 115oC.
At 80oCthe reaction mass is in molten state and after reaching 115oC the reaction gets
completed.
Further, it is an embodiment of the present invention wherein the reaction is performed for
a period of time ranging from 20 minutes to 2 hours.
Still it is an embodiment of the present invention wherein the amount of Ondansetron
prepared is more than 80% yield.

Another embodiment of the present invention wherein l,2,3,9-tetrahydro-9-methyl-3-[(2-
mcthyl-lH-imidazol-l-yl)methyl]-4H-carbazol-4-one obtained is free from exomethylene
carbazolone impurity.
We have described above the invention with respect to particular embodiments; the
invention is further defined by reference to the following examples describing in detail the
preparation and composition of the invention. It will be apparent to those skilled in the art
thai many modifications, both to materials and methods, may be practiced without
departing from the purpose and interest of the invention.
The process of the present invention is described by the following examples, which are
illustrative only and should not be construed as limit to the scope of the reaction in any
manner.
EXAMPLES EXAMPLE 1 Preparation of l,2,3,9-tetrahydro-9-methyl-3-[(2-inethyl-lH-imidazol- yl)inethyl]-
4H-carbazol-4-one
A mixture containing 20g (0.068 mole) of 3-[(dimethylamino) methyl]-l,2,3,9-tetrahydro-9-methyl-4H-carbazol-4-one hydrochloride and 20g (0.246 mole) of 2-methylimidazole is healed to melt at 100-100oC, after few minutes reaction mass starts to solidify and the reaction mass is stirred at 75-85°C for about 2 hours. 80ml of water is added to the reaction mass and stirred it for 1 hour at room temperature followed by cooling of the reaction mass. The precipitated crude Ondansetron is filtered off and dried. The weight of dried Ondansetron base is 19.8g (yield - 99%) having 95% HPLC purity and melting point is220-221"C.
EXAMPLE 2
Preparation of l,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-lH-imidazoI-l-yl)methy!]-
4H-carbazol-4-one
A mixture containing 10g (0.034 mole) of 3-[(dimethylamino) methyl]-l,2,3,9-tetrahydro-9-methyl-4H-carbazol-4-one hydrochloride and 10g (0.121 mole) of 2-methylimidazole is heated to melt at 110-115oC, after few minutes reaction mass starts to solidify and the reaction mass is stirred at 75-85oC for about 1 hour. 60ml of water is added to the reaction mass and stirred it for 1 hour at room temperature followed by cooling of the reaction

mass. The precipitated crude Ondansetron is filtered off and dried. The weight of the dried Ondansetron base is 9.6g (yield-96%) having >94% HPLC purity.
EXAMPLE 3
Preparation of l,2,359-tetrahydro-9-methyl-3-[(2-methyl-lH-imidazol-l- yl)methyl]-
4H-carbazol-4-one
A mixture containing 50g (0.17 mole) of 3-[(dimethylamino) methyl]"l,2,3,9-tetrahydro-9-methy]-4H-carbazol-4-one hydrochloride and 50g (0.60 mole) of 2-methylimidazole is heated to melt at 110-115oC, after few minutes reaction mass starts to solidify and further the reaction mass is stirred at 75-85oC for about 20 minutes. The molten mass was quenched to around 300 ml ice-water mixture under vigorous stirring for 1 hour at room temperature at room temperature followed by cooling of the reaction mass. The precipitated crude Ondansetron is filtered off and dried. The weight of the dried Ondansetron base is 46g (yield-92%) having >94% HPLC purity.
EXAMPLE 4
Preparation of l,2,3,9-tetrahydro-9-inethyl-3-[(2-methyl-lH-imidazoM- yl)methyi]-
4H-carbazol-4-one
A mixture containing 200g (0.683 mole) of 3-[(dimethylamino) methylJ-1,2,3,9-tctrahydro-9-methyl-4H-carbazol-4-one hydrochloride and 200g (1.21 mole) of 2-melhylimidazole is heated to melt at 110-115oC, after few minutes reaction mass starts to solidify and the reaction mass is stirred at 75-85oC for about 1 hour. 1500ml of water is added to the reaction mass and stirred it for 1 hour at room temperature at room temperature followed by cooling of the reaction mass. The precipitated crude Ondansetron is filtered off and dried. The weight of the dried Ondansetron base is 190g (yield - 94.8%) having 98.36% HPLC purity and melting point is 220-221''C. Recrystallization of crude Ondansetron:
The crude Ondansetron prepared from Example 4 (25g) and methanol (1100ml) are charged in a 3 litre round-bottomed flask at room temperature and then refluxed the mass at 64oC. The resulting solution is stirred with charcoal (5%, w/w) at 64oC for one hour and then the charcoal is filtered off. The filtrate is transferred to another round-bottomed flask and distilled out 830ml of methanol. The solution is then cooled to room temperature;

further cooled to 20°C and filtered the slurry mass, melting point is 235-236°C . The wet solid mass once again dissolved in 700ml of methanol under reflux to obtain a clear solution and further it is refluxed for another 30 minutes. Approximately 490ml of methanol is distilled off, the slurry mass is cooled and filtered under suction. After drying the wet compound at 40°C-45°C over a period of time of 6-8 hours the Ondansetron pure base is obtained (20g, yield - 80%) with HPLC purity of 99.98% and the melting point is 242-243°C. The ondansetron base obtained is free from exomethylene carbazolone impurity and the only impurity present is IH-imidazole (0.02%) and the product complies with US and British pharmacopoeia specification. Advantages of the invention
1. The present invention provides a process, which does not require any solvent, so the capacity at industrial scale can be more.
2. The present invention provides a process for preparation of Ondansetron wherein Ondansetron is obtained in high yield at a shorter reaction time.
3. The process of the present invention is very simple and provides pure
tetrahydrocabazolone derivatives.
4. The present invention provides a process for the preparation of ondansetron free from
the impurity exomethylene carbazolone.

We claim
1. A process for preparing tetrahydrocarbazolone derivatives of Formula (A)

wherein Rl represents a hydrogen atom, a C1-10 alkyl, a C3.7 cycloalkyl-(C1-4) alkyl group, a C3-10 alkynyl group, a phenyl or a phenyl-Ci.3 alkyl group; and R2, R3 and R4 each independently represents a hydrogen atom, a C1-6 alkyl, a C3.7 cycloalkyl, a C2-6 alkenyl or a phenyl-(C1-3) alkyl group, and at least two groups independently represent a hydrogen atom or a C1-6 alkyl group; said process comprising of; a) mixing a compound of Formula (B)

wherein Rl represents a hydrogen atom, a C1-10 alkyl, a C3-7 cycloalkyl-(C1-4) alkyl group, a C3.10 alkynyl group, a phenyl or a phenyl-C1-3 alkyl group, Y represents a reactive substituent and hydrogen halide is hydrogen fluoride, hydrogen chloride, hydrogen bromide, or hydrogen iodide or a protected derivative thereof with an imidazole of Formula (C)


wherein R2, R3 and R4 each independently represents a hydrogen atom, a C1-6 alkyl, a C3-7 cycloalkyl, a C2-6 alkenyl or a phenyl-(C1-3) alkyl group and at least two groups independently represent a hydrogen atom or a C1-6 alkyl group
in absence of solvent to obtain a corresponding reaction mixture of compound of Formula (B) and compound of Formula (C),
b) melting said reaction mixture at a temperature in the range of 80°C to 180°C ,
c) stirring the reaction mixture at 85°C for a period of time in the range of 20 minutes to 2 hours, and
d) obtaining tetrahydrocarbazolone derivative by adding water to the reaction mixture and stirring for 1 hour at room temperature followed by cooling the reaction mixture.

2. The process as claimed in claim 1, wherein the compound of Formula (C) is employed in an amount ranging from 1.2 to 3.5 molar equivalents based on the amount of the compound of Formula (B).
3. The process as claimed in claim 1, wherein
a. Rl is methyl,
b. R2 is methyl,
c. R3 is hydrogen,
d. R4 is hydrogen,
e. Hydrogen halide is hydrochloride, and
f. Y is dimethylamino methyl group.
4. The process for preparing tetrahydrocarbazolone derivatives as claimed in claim 1,
wherein said tetrahydrocarbazolone derivative is l,2,3,9-tetrahydro-9-methyl-3-
[(2-methyl-lH-imidazol-l-yl)methyl]-4H-carbazol-4-one of Formula (I)


5. A process for preparing l,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-lH-imidazol-l-yl)methyl]-4H-carbazol-4-one of Formula (I)

comprises;
a) mixing 3-[(dimethylamino)methyl]-l,2,3,9-tetrahydro-9-methyl-4H-
carbazol-4-one hydrochloride of Formula (D)


in the absence of solvent to obtain a corresponding reaction mixture of compound of Formula (D) and Formula (E),
b) melting said reaction mixture at a temperature in the range of 80°C to
180°C ,
c) stirring the reaction mixture at 85°C for a period of time ranging from 20
minutes to 2 hours, and
d) obtaining l,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-lH-imida2ol-l-
yl)methyl]-4H-carbazol-4-one by adding water to the reaction mixture and
stirring for 1 hour at room temperature followed by cooling the reaction
mixture.
6. The process as claimed in claim 5, wherein the compound of Formula (E) is employed in an amount ranging from 1,2 to 3.5 molar equivalents based on the amount of the compound of Formula (D).
7. The process as claimed in claims 1 or 5, wherein the reaction is performed at a temperature ranging from 80°C to 180°C .
8. The process as claimed in claims 1 or 5, wherein the reaction is performed at a
temperature between 100°C to 115°C .
9. The process as claimed in claims 1 or 5, wherein the reaction is performed for a
period of time from 20 minutes to 2 hours.
10. The process as claimed in claim 5, wherein l,2,3,9-tetrahydro-9-methyl-3-[(2-
methyl-lH-imidazol-l-yl)methyl]-4H-carbazol-4-one is free from exomethylene
carbazolone impurity.