FORM 2
THE PATENT ACT, 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)
Title of the invention
"A process for the preparation of prasugrel and its pharmaceutically acceptable salts thereof by using novel intermediate 5,6,7,7a-tetrahydro-thieno [3,2-c] pyridine-2(4H)-one hydrobromide"
Enaltec Labs Pvt. Ltd. an Indian Company, having its Registered Office at 17thFloor, Kesar Solitaire, Plot No.5 Sector-19, Sanpada, Navi Mumbai Maharashtra, India. Pin Code: 400705
1. The following specification particularly describes the invention and the manner in which it is to be performed.

A process for the preparation of prasugrel and its pharmaceutically acceptable salts thereof by using novel intermediate 5,6,7,7a-tetrahydro-thieno [3,2-c] pyridine-2(4H)-one hydrobromide
Field of the invention
The present inventions provide novel intermediate 5, 6, 7,7a-tetrahydro-thieno [3, 2-c] pyridine-2(4H)-one hydrobromide and its use in a process of preparing prasugrel and its pharmaceuticaJly acceptable salts thereof.
Background of the invention
Prasugrel hydrochloride is chemically 2-Acetoxy-5-(a-cyclopropylcarbonyl-2-fluorobenzyl)-4, 5, 6, 7-tetrahydrothieno [3, 2-c] pyridine hydrochloride and is known from U.S Patent No. 6,693,115 and is represented by the compound of structural formula I.

Prasugrel hydrochloride is marketed in USA under brand name Efftent and is indicated to reduce the rate of thrombotic cardiovascular (CV) events in patients with acute coronary syndrome (ACS).
U.S Patent No. 5,288,726 describes prasugrel or a pharmaceutically acceptable salt thereof generically. The prasugrel is being prepared by condensing 5, 6, 7, 7a-tetrahydro-thieno [3, 2-c] pyridine-2(4H)-one hydrochloride compound of structural formula II and α-cyclopropylcarbonyl-2-fluorobenzyl bromide compound of structural formula III in the presence of potassium bicarbonate to afford l-cyclopropyl-2-(2-fluorophenyl)-2-(2-hydroxy-6, 7-

dihydrothieno [3, 2-c] pyridin-5(4H)-yl) ethanone compound of structural formula IV, followed by the acetyJation with acetic anhydride in the presence of sodium hydride as shown in scheme I.

The specification of PCT publication no. 2009/066326 describe that detritylation of 5-trityl-5, 6, 7, 7a-tetrahydrothieno [3, 2-c] pyridin-2(4H)-one compound of structural formula VIII may be carried out by inorganic acids such as hydrobromic acid and phosphoric acid. However the detritylation of 5-trityl-5, 6, 7, 7a-tetrahydrothieno [3, 2-c] pyridin-2(4H)-one compound of structural formula VIII is being carried out with p-toluene sulfonic acid in tetrahydrofuran solvent in example no. 17.
The present inventors have found that prior-art processes such as those described in U.S Patent No. 5,288,726 and PCT publication no. 2009/062044 produces prasugrel hydrochloride with contamination of 2-(3-((N-acetylacetamido) methyl)-5-oxo-2, 5-dihydrothiophen-2-yl) ethyl acetate compound of structural formula VI.


2-(3-((N-acetylacetamido) methyl)-5-oxo-2, 5-dihydrothiophen-2-yl) ethyl acetate compound of structural formula VI is being formed during the acetylation of l-cyclopropyl-2-(2-fluorophenyl)-2-(2-hydroxy-6, 7- dihydrothieno [3, 2-c] pyridin-5(4H)-yl) ethanone compound of structural formula IV with acetic anhydride in the presence of base.
l-cyclopropyl-2-(2-fluorophenyl)-2-(2-hydroxy-6, 7- dihydrothieno [3, 2-c] pyridin-5(4H)-yl) ethanone compound of structural formula IV produces by following prior-art processes such as those described in U.S Patent No. 5,288,726 and PCT publication no. 2009/062044; 2009/066326 is always contaminated with 4-(aminomethyl)-5-(2-hydroxyethyl) thiophen-2(5H)-one hydrochloride compound of structural formula VII and p-toluene sulfonic acid salt of 4-(aminomethyl)-5-(2-hydroxyethyl) thiophen-2(5H)-one compound of structural formula X.

4-(aminomethyl)-5-(2-hydroxyethyl) thiophen-2(5H)-one hydrochloride compound of structural formula VII is being produced during the detritylation of 5-trityl-5,6,7,7a-tetrahydrothieno[3,2-c]pyridin-2(4H)-one compound of structural formula VIII with hydrochloric acid as depicted in scheme II.


p-toluene sulfonic acid salt of 4-(aminomethyl)-5-(2-hydroxyethyl) thiophen-2(5H)-one compound of structural formula X is being produced during the detritylation of 5-trityl-5,6,7,7a-tetrahydrothieno[3,2-c]pyridin-2(4H)-one compound of structural formula VIII with p-toluene sulfonic acid herein after referred as ptsa as depicted in scheme III.

Accordingly there is a need in the art to develop a process for preparing prasugrel and its pharmaceutically acceptable salts thereof which overcomes the formation of 2-(3-((N-acetylacetamido) methyl)-5-oxo-2, 5-dihydrothiophen-2-yl) ethyl acetate compound of structural formula VI.


Summary of the invention:
A first aspect of the present invention is to provide a process for preparing prasugrel and its pharmaceutically acceptable salts thereof comprising the steps of:
a. detritylating 5-trityl-5, 6, 7, 7a-tetrahydrothieno[3,2-c]pyridin-2(4H)-one compound of structural formula VIII with hydrobromic acid to produce crystalline 5, 6, 7, 7a-tetrahydro-thieno [3, 2-c] pyridine-2(4H)-one hydrobromide compound of structural formula IX having XRD pattern as depicted in figure 1;

b. reacting crystalline 5, 6, 7, 7a-tetrahydro-thieno [3, 2-c] pyridine-2(4H)-one hydrobromide compound of structural formula IX having XRD pattern as depicted in figure 1 with α-cyclopropylcarbonyl-2-fluorobenzyl bromide compound of structural formula III in organic solvent in the presence of base to produce l-cyclopropyl-2-(2-fluorophenyl)-2-(2-hydroxy-6, 7- dihydrothieno [3, 2-c] pyridin-5(4H)-yl) ethanone compound of structural formula IV;

c. acetylating l-cyc]opropyl-2-(2-fluorophenyl)-2-(2-hydroxy-6, 7- dihydrothieno [3, 2-c] pyridin-5(4H)-yl) ethanone compound of structural formula IV with acetylating agent in organic solvent in the presence of base to produce prasugrel compound of structural formula V and


d. optionally converting prasugrel compound of structural formula V into its pharmaceutically acceptable salts thereof.
A second aspect of the present invention is to provide a use of substantially pure crystalline 5, 6, 7, 7a-tetrahydro-thieno [3, 2-c] pyridine-2(4H)-one hydrobromide compound of structural formula IX having XRD pattern as depicted in figure 1 for the preparation of prasugrel and its pharmaceutically acceptable salts thereof.

A third aspect of the present invention is to provide substantially pure prasugrel and its pharmaceutically acceptable salts thereof free from 2-(3-((N-acetylacetamido) methyl)-5-oxo-2, 5-dihydrothiophen-2-yl) ethyl acetate compound of structural formula VI.

A fourth aspect of the present invention is to provide a process for the preparation of crystalline 5, 6, 7, 7a-tetrahydro-thieno [3, 2-c] pyridine-2(4H)-one hydrobromide compound of structural formula IX having XRD pattern as depicted in figure 1 comprises detritylation of 5-trityl-5, 6, 7,

7a-tetrahydrothieno [3, 2-c] pyridin-2(4H)-one compound of structural formula VIII with hydrobromic acid.

A fifth aspect of the present invention is to provide substantially pure crystalline 5, 6, 7,7a-tetrahydro-thieno [3, 2-c] pyridine-2(4H)-one hydrobromide compound of structural formula IX free from 4-(aminornethyl)-5-(2-hydroxyethyl) thiophen-2(5H)-one compound of structural formula XII.

Another aspect of the present invention is to provide novel intermediate 5, 6, 7,7a-tetrahydro-thieno [3, 2-c] pyridine-2(4H)-one hydrobromide compound of structural formula IX

Another aspect of the present invention is to provide novel compounds of structural formula VI, VII, X and XII


Detailed description of the invention:
The 5-trityl-5, 6, 7,7a-tetrahydrothieno[3,2-c]pyridin-2(4H)-one compound of structural formula VIII may be prepared by following prior-art methods such as those described in PCT publication nos. 2009/066326 and 2009/062044, which are incorporated herein by reference only.
The detritylation of 5-trityl-5, 6, 7, 7a-tetrahydrothieno [3, 2-c] pyridin-2(4H)-one compound of structural formula VIII may be carried out with hydrobromic acid in an organic solvents to produce crystalline 5, 6, 7, 7a-tetrahydro-thieno [3, 2-c] pyridine-2(4H)-one hydrobromide compound of structural formula IX having XRD pattern as depicted in figure 1.
Examples of organic solvent may include aromatic hydrocarbon, halogenated hydrocarbon, alcohol, ketone and alkyl acetate solvents.
Examples of aromatic hydrocarbon solvent may include toluene, xylenes, cresol or mixture(s) thereof.
Examples of halogenated hydrocarbon solvent may include dichloromethane, dichloroethane, chloroform, carbon tetrachloride or mixture(s) thereof.
Examples of alcohol solvent may include methanol, ethanol, n-propanol. isopropanol, n-butanol, isobutanol, n-pentanol, isopentanol or mixture(s) thereof.

Examples of alkyl acetate solvent may include ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, tertiary butyl acetate, pentyl acetate or mixture(s) thereof.
Examples of ketone solvent may include acetone, methyl ethyl ketone, methyl isobutyl ketone, dibutyl ketone, diethyl ketone, dipropyl ketone, diisopropyl ketone, methyl butyl ketone, methyl propyl ketone, methyl isopropyl ketone, ethyl isopropyl ketone or mixture(s) thereof.
The detritylation of 5-trityl-5, 6, 7, 7a-tetrahydrothieno [3, 2-c] pyridin-2(4H)-one compound of structural formula VIII with hydrobromic acid may be carried out at a temperature in the range of 30°C to 70°C for 3 hours to 7 hours.
The crystalline 5, 6, 7,7a-tetrahydro-thieno [3, 2-c] pyridine-2(4H)-one hydrobromide compound of structural formula IX may be isolated by the steps of filtration, washing, drying or combination thereof.
The crystalline 5, 6, 7,7a-tetrahydro-thieno [3, 2-c] pyridine-2(4H)-one hydrobromide compound of structural formula IX may be filtered under reduced pressure.
The crystalline 5, 6, 7,7a-tetrahydro-thieno [3, 2-c] pyridine-2(4H)-one hydrobromide compound of structural formula IX may be washed with ketone solvents.
The crystalline 5, 6, 7,7a-tetrahydro-thieno [3, 2-c] pyridine-2(4H)-one hydrobromide compound of structural formula IX may be dried at a temperature in the range of 45°C to 60°C for the period of 2 hours to 6 hours under reduced pressure.
The isolated 5, 6, 7,7a-tetrahydro-thieno [3, 2-c] pyridine-2(4H)-one hydrobromide compound of structural formula IX may be crystalline in nature.
The crystalline 5, 6, 7,7a-tetrahydro-thieno [3, 2-c] pyridine-2(4H)-one hydrobromide compound of structural formula IX may be characterized by an x-ray powder diffraction spectrum having

peaks expressed as 29 at 15.7, 16.8, 19.7, 23.5, 23.7, 26.5, 27,7, 29.0, 30.2, 33.6, 33.9, 35.3 and 35.7 ±0.2 degrees.
The crystalline 5, 6, 7,7a-tetrahydro-thieno [3, 2-c] pyridine-2(4H)-one hydrobromide compound of structural formula IX may be further characterized by x-ray powder diffraction spectrum having peaks expressed as 20 at 16.8, 23.5, 23.7, 29.0 and 33.6 ± 0.2 degrees.
The crystalline 5, 6, 7,7a-tetrahydro-thieno [3, 2-c] pyridine-2(4H)-one hydrobromide compound of structural formula IX may be further characterized by x-ray powder diffraction spectrum having peaks expressed as 20 at 16.8, 23.5 and 29.0 ± 0.2 degrees.
The crystalline 5, 6, 7,7a-tetrahydro-thieno [3, 2-c] pyridine-2(4H)-one hydrobromide compound of structural formula IX may contain less than 0.15% wt /wt of 4-(aminomethyl)-5-(2-hydroxyethyl) thiophen-2(5H)-one compound of structural formula XII.

The crystalline 5, 6, 7,7a-tetrahydro-thieno [3, 2-c] pyridine-2(4H)-one hydrobromide compound of structural formula IX may be characterized by x-ray powder diffraction spectrum having following peaks with d-spacing [A] and relative intensity [%].

Pas. [°2Th.] d-spacing [A] Rei. Int. [%]
15.7941 5.61115 11.44
16.8369 5.26591 53.73
19.7202 4.50201 36.97
23.5919 3.77120 100.00
23.7463 3.74704 36.67
26.5426 3.35830 16.77
27.7927 3.21001 27.12
29.0439 3.07452 51.43

30.2216 2.95733 16.32
33.6227 2.66556 24.02
33.9193 2.64293 11.35
35.3784 2.53720 10.80
35.7138 2.51414 12.67
The reaction of crystalline 5, 6, 7, 7a-tetrahydro-thieno [3, 2-c] pyridine-2(4H)-one hydrobromide compound of structural formula IX having XRD pattern as depicted in figure 1 with α-cyclopropylcarbonyl-2-fluorobenzyl bromide compound of structural formula III may be carried out in organic solvent in the presence of base to produce l-cyclopropyl-2-(2-fluorophenyl)-2-(2-hydroxy-6, 7- dihydrothieno [3, 2-c] pycidin-5(4H)-yl) ethanone compound of structural formula IV.
The α-cycIopropylcarbonyl-2-fluorobenzyl bromide compound of structural formula III may be prepared by methods known in the art such as those described in PCT publication nos. 2009/066326 and 2009/062044, which are incorporated herein by reference only.
The examples of organic solvent selected from the group comprising of diisopropyl ether, methyl tertiary butyl ether, diethyl ether, diisopropyl ether, tetrahydrofuran, dimethyl formamide, dimethyl sulfoxide, dimethoxy ethane, diethyl ketone, acetone, ethyl acetate, propyl acetate, butyl acetate, pentyl acetate, acetonitrile, propionitrile or mixture(s) thereof.
The examples of base may include inorganic base or organic base.
The examples of inorganic base may include alkali metal carbonates such as sodium carbonate, potassium carbonate; or alkali metal hydroxides such as sodium hydroxide, potassium hydroxide; or alkali metal bicarbonates such as sodium bicarbonate and potassium carbonate.
The examples of organic base may be selected from the group comprising of triethylamine, tributylamine, diisopropyl ethyl amine , pyridine, N-methyl morpholine, 4-ethyl morpholine, N,N-diethylethanamine or mixture(s) thereof.

The reaction of crystalline 5, 6, 7, 7a-tetrahydro-thieno [3, 2-c] pyridine-2(4H)-one hydrobromide compound of structural formula IX having XRD pattern as depicted in figure 1 with a-cyclopropylcarbonyl-2-fluorobenzyl bromide compound of structural formula III may be carried out at a temperature in the range of-5°C to +5°C for a period of 2 hours to 8 hours.
The l-cyclopropyl-2-(2-fluorophenyl)-2-(2-hydroxy-6, 7- dihydrothieno [3, 2-c] pyridin-5(4H)-yl) ethanone compound of structural formula IV may be isolated from the reaction mixture by diluting the reaction mixture with ether solvents, separating organic layer, washing organic layer with water and then distilling ether solvents from the organic layer under reduced pressure. The acetylation of l-cyclopropyl-2-(2-fluorophenyl)-2-(2-hydroxy-6, 7- dihydrothieno [3, 2-c] pyridin-5(4H)-yl) ethanone compound of structural formula IV may be carried out with acetylating agent in organic solvent in the presence of base to produce prasugrel compound of structural formula V.
Examples of acetylating agent may include acetic anhydride or acetyl chloride.
Examples of organic solvent may be selected from the group comprising of dimethyl formamide, dimethyl acetamide, dimethyl sulfoxide, acetonitrile, tetrahydrofuran, dioxane or mixture(s) thereof.
Examples of base may include inorganic or organic base as described above in the specification.
The prasugrel compound of structural formula V may be isolated from the reaction mixture by quenching the excess acetylating agent with saturated ammonium chloride, followed by the extraction with alkyl acetate solvents and crystallization in alcoholic solvents.
Examples of alkyl acetate solvent may include ethyl acetate, propyl acetate, butyl acetate, pentyl acetate, isobutyl acetate or mixture(s) thereof.
Examples of alcoholic solvent may include methanol, ethanol, propanol, isopropanol, butanol, isobutanol, pentanol or mixture(s) thereof.

The prasugrel compound of structural formula V may be further purified by the recrystallization in a mixture of ketone, ether and aromatic hydrocarbon solvents.
Examples of ketone solvent may include acetone, methyl isobutyl ketone, diethyl ketone, dipropyl ketone, methyl ethyl ketone, methyl propyl ketone or methyl isopropyl ketone.
Examples of ether solvent may include tetrahydrofuran, dioxane, diethyl ether, diisopropyl ether, dibutyl ether, methyl tertiary butyl ether, methyl ethyl ether or methyl isobutyl ether.
Examples of aromatic hydrocarbon solvent may include toluene, cyclohexane or xylene.
The recrystallization of prasugrel compound of structural formula V may be carried out at a temperature in the range of 30 to 80°C
The prasugrel compound of structural formula V may be converted into its pharmaceutically acceptable salts thereof by treating prasugrel compound of structural formula V with corresponding acid in organic solvents.
Examples of acid may include hydrochloric acid, hydrobromic acid, benzenesulfonic acid, maleic acid, malic acid, fumaric acid, citric acid, succinic acid, oxalic acid or p-toluene sulfonic acid.
Examples of organic solvent may include toluene, tetrahydrofuran, diethyl ether, acetonitrile, methanol, ethanol, propanol, isopropanol, butanol, isobutanol, pentanol, methyl ethyl ketone, acetone, methyl isobutyl ketone or diethyl ketone.
Preferred examples of pharmaceutically acceptable salts of prasugrel compound of structural formula V may include prasugrel hydrochloride and prasugrel hydrobromide.
The prasugrel hydrochloride may be isolated from the reaction mixture by the steps comprising of cooling, filtration, washing, drying or combination thereof.

The prasugrel hydrochloride may be dried at a temperature in the range of 45°C to 65°C for a period of 4 hours to 10 hours.
The substantially pure prasugrel and its pharmaceutic ally acceptable salts thereof may contain less than 0.15% wt/wt of 2-(3-((N-acetylacetamido) methyl)-5-oxo-2, 5-dihydrothiophen-2-yl) ethyl acetate compound of structural fonnula VI.

The term "Substantially pure" described in the specification refers to the HPLC purity more than 99.5%.
Description of the Figure:
Figure 1 depicts the XRD pattern of crystalline 5, 6, 7,7a-tetrahydro-thieno [3, 2-c] pyridine-2(4H)-one hydrobromide compound of structural formula IX.
Instrumental parameters for XRD analysis:
Goniometer=PW3050/60 (Theta/Theta); Minimum step size 2Theta:0.001; Minimum step size
Omega: 0.001
Sample stage=Spinner PW3064
Diffractometer system=XPERT-PRO
Measurement program-15 min programme,
Scan Axis Gonio
Start Position [°2Th.] 2.0084
End Position [°2Th.] 39.9864
Step Size [°2Th.] 0.0170

Scan Step Time [s] 51.0404
Scan Type Continuous
PSD Mode Scanning
PSD Length [°2Th.] 2.12
Offset [°2Th.] 0.0000
Divergence Slit Type Automatic
Irradiated Length [mm] 10.00
Specimen Length [mm] 10.00
Measurement Temperature [°C] 25.00
Anode Material Cu
K-Alphal [A] 1.54060
K-Alpha2[A] 1.54443
K-Beta [A] 1.39225
K-A2 / K-Al Ratio 0.50000
Generator Settings 40 mA, 45 kV
Diffractometer Type 0000000011010329
Diffractometer Number 0
Goniometer Radius [mm] 240.00
Dist. Focus-Diverg. Slit [mm] 100.00
Incident Beam Monochromator No
Spinning Yes
Examples
In the following example, the preferred embodiments of the present invention are described only by way of illustrating the process of the invention. However, these are not intended to limit the scope of the present invention in any way.

Example 1: Preparation of Prasugrel hydrochloride
Step 1: Preparation of crystalline 5, 6, 7, 7a-tetrahydro-thieno [3, 2-c] pyridine-2(4H)-one hydrobromide compound of structural formula IX
A solution of 5-trityl-5, 6, 7, 7a-tetrahydrothieno [3, 2-c] pyridin-2(4H)-one compound of structural formula VIII (50 grams) in acetone (850 ml) was added concentrated hydrobromic acid (48%, 19 grams) at 30°C and resulting reaction mixture was refluxed for 5 hours. Then the reaction mixture was cooled to 20-25°C and stirred for 90 minutes. The precipitated solid was filtered, washed with acetone (50 ml) and then dried at 50-55°C to get the title compound. Yield: 20.48 grams
Step 2: Preparation of l-cyclopropyl-2-(2-fluorophenyl)-2-(2-hydroxy-6, 7- dihydrothieno [3, 2-c] pyridin-5(4H)-yl) ethanone compound of structural formula IV
A solution ofα-cyclopropylcarbonyl-2-fluorobenzyl bromide (25 grams) in acetonitrile (75 ml) was added powder potassium carbonate (28.52 grams) at 0-5°C and then crystalline 5, 6, 7. 7a-tetrahydro-thieno [3, 2-c] pyridine-2(4H)-one hydrobromide compound of structural formula JX (20.48 grams) was added in 5 lots at 0-5°C and resulting reaction mixture was stirred for 5 hours. Then the reaction mixture was diluted with diisopropyl ether (750 ml), organic layer separated, washed with water (2x650 ml), and then diisopropyl ether from the organic layer was distilled off completely to get the title compound. Yield: 22 grams
Step 3: Preparation of Prasugrel
A solution of l-cyclopropyl-2-(2-fluorophenyl)-2-(2-hydroxy-6, 7- dihydrothieno [3, 2-c] pyridin-5(4H)-yl) ethanone (20 grams) in dimethyl formamide (75 ml) was added acetic anhydride (9.23grams) at 0-5°C and then sodium hydride (2.41 grams) was added in 5 lots at 0-5°C. The resulting reaction mixture was heated up to 30°C and stirred for 2 hours. The reaction mixture was quenched with saturated ammonium chloride (100 ml) solution, extracted with ethyl

acetate (2 x 100 ml), washed with sodium chloride solution (100 ml) and then concentrated under reduced pressure to get residue. The residue was crystallized in methanol solvent (40 ml) to get title compound. Yield: 8.4 grams
Step 4: Purification of Prasugrel
A solution of Prasugrel (5 grams) in acetone (10 ml) was refluxed for 10 minutes and then
cyclohexane (20 ml) was added and resulting solution was stirred for 20 minutes at 55-60°C, The
reaction mixture was cooled to 0-5°C, stirred for 1 hour and then resulting solids were filtered,
washed with cyclohexane (5 ml) and dried at 55-60°C under reduced pressure to get purified
prasugrel.
Yield: 3.6 grams
Purity: 99.6% (By HPLC)
Step 5: Preparation of Prasugrel hydrochloride
A solution of prasugrel (8 grams) in acetone (80 ml) was added drop wise isopropanol. hydrochloric acid (6.45 grams) at 20-25°C and resulting reaction mixture was stirred for 1 hour. The precipitated solid was filtered, washed with acetone (16 ml) and dried at 60°C for 10 hours. Yield: 6.$ grams Purity: 99.6% (By HPLC)

We claim:
1. A process for preparing prasugrel and its pharmaceutic ally acceptable salts thereof comprising
the steps of:
a. detritylating 5-trityl-5, 6, 7, 7a-tetrahydrothieno[3,2-c]pyridin-2(4H)-one compound of structural formula VIII with hydrobromic acid to produce crystalline 5, 6, 7, 7a-tetrahydro-thieno [3, 2-c] pyridine-2(4H)-one hydrobromide compound of structural formula IX having XRD pattern as depicted in figure 1;

b. reacting crystalline 5, 6, 7, 7a-tetrahydro-thieno [3, 2-c] pyridine-2(4H)-one hydrobromide compound of structural formula IX having XRD pattern as depicted in figure I with a-cyclopropylcarbonyl-2-fluorobenzyl bromide compound of structural formula III in organic solvent in the presence of base to produce l-cyclopropyl-2-(2-fluorophenyl)-2-(2-hydroxy-6, 7- dihydrothieno [3, 2-c] pyridin-5(4H)-yl) ethanone compound of structural formula IV;

c. acetylating l-cyclopropyl-2-(2-fluorophenyl)-2-(2-hydroxy-6, 7- dihydrothieno [3, 2-c] pyridin-5(4H)-yl) ethanone compound of structural formula IV with acetylating agent in organic solvent in the presence of base to produce prasugrel compound of structural formula V and


d. optionally converting prasugrel compound of structural formula V into its pharmaceutically acceptable salts thereof.
2. Use of substantially pure crystalline 5, 6, 7, 7a-tetrahydro-thieno [3, 2-c] pyridine-2(4H)-one hydrobromide compound of structural formula IX having XRD pattern as depicted in figure 1 for the preparation of prasugrel and its pharmaceutically acceptable salts thereof.

4. A compounds of structural formula IX VI, VII, X and XII
3. A process for the preparation of crystalline 5, 6, 7, 7a-tetrahydro-thieno [3, 2-c] pyridine-2(4H)-one hydrobromide compound of structural formula IX having XRD pattern as depicted in figure 1 comprises detritylation of 5-trityl-5, 6, 7, 7a-tetrahydrothieno [3, 2-c] pyridin-2(4H)-one compound of structural formula VIII with hydrobromic acid.



5. The process according to claim nos 1 and 3 wherein detritylation of 5-trityI-5, 6, 7, 7a-tetrahydrothieno [3, 2-c] pyridin-2(4H)-one compound of structural formula VIII is carried out with hydrobromic acid in an organic solvents such as aromatic hydrocarbon, halogenated hydrocarbon, alcohol, ketone and alkyl acetate solvents.
6. The process according to claim no 5, wherein aromatic hydrocarbon solvent include toluene, xylenes, cresol or mixture(s) thereof; halogenated hydrocarbon solvent include dichloromethane, dichloroethane, chloroform, carbon tetrachloride or mixture(s) thereof; alcohol solvent include methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, n-pentanol, isopentanol or mixture(s) thereof; alkyl acetate solvent include ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, tertiary butyl acetate, pentyl acetate or mixture(s) thereof; ketone solvent include acetone, methyl ethyl ketone, methyl isobutyl ketone, dibutyl ketone, diethyl ketone, dipropyl ketone, diisopropyl ketone, methyl butyl ketone, methyl propyl ketone, methyl isopropyl ketone, ethyl isopropyl ketone or mixture(s) thereof.
7. The process according to claim nos 1 and 3 wherein detritylation of 5-trityl-5, 6, 7, 7a-tetrahydrothieno [3, 2-c] pyridin-2(4H)-one compound of structural formula VIII is carried out at a temperature in the range of 30°C to 70°C for 3 hours to 7 hours.

8. The process according to claim nos 1 to 3 wherein crystalline 5, 6, 7,7a-tetrahydro-thieno [3, 2-c] pyridine-2(4H)-one hydrobromide compound of structural formula IX is characterized by an x-ray powder diffraction spectrum having peaks expressed as 29 at 15.7, 16.8, 19.7, 23.5, 23.7, 26.5, 27.7, 29.0, 30.2, 33.6, 33.9, 35.3 and 35.7 ± 0.2 degrees.
9. The process according to claim nos 1 to 3 wherein crystalline 5, 6, 7,7a-tetrahydro-thieno [3, 2-c] pyridine-2(4H)-one hydrobromide compound of structural formula IX contain less than 0.15% wt /wt of 4-(aminomethyl)-5-(2-hydroxyethyl) thiophen-2(5H)-one compound of structural formula XII.

10. The process according to claim no.l wherein reaction of crystalline 5, 6, 7, 7a-tetrahydro-thieno [3, 2-c] pyridine-2(4H)-one hydrobromide compound of structural formula IX having XRD pattern as depicted in figure 1 with a-cyclopropyIcarbonyl-2-fluorobenzyl bromide compound of structural formula III is carried out at a temperature in the range of-5°C to +5°C for a period of 2 hours to 8 hours.