FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)
1. TITLE OF THE INVENTION:
A process for the preparation of Prazosin Hydrochloride
2. APPLICANT (S)
(a) NAME: Enaltec Labs Pvt. Ltd.
(b) NATIONALITY:
An Indian Company incorporated under the Indian Companies ACT 1956
(c) ADDRESS:
Enaltec Labs Pvt. Ltd., 17th Floor, Kesar Solitaire, Plot No. 5, Sector 19, Sanpada, Navi Mumbai- 400705, Maharashtra, India.
3. PREAMBLE TO THE DESCRIPTION
The following specification particularly describes the invention and the manner in which it is to be performed

Technical field of the invention:
The present invention relates to a process for the preparation of Prazosin Hydrochloride represented by compound of Formula I.

Background of the invention:
Prazosin Hydrochloride (compound of formula I) is chemically known as hydrochloride salt of l-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-furoyl) piperazine. Also chemically known as [4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-l-yl]-(furan-2-yl)methanone hydrochloride represented by compound of Formula I.
Prazosin is a synthetic piperazine derivative and an alpha-1 adrenergic receptor inhibitor used primarily as an anti-hypertensive.
Prazosin Hydrochloride (Formula I) approved by USFDA with brand name MINIPRESS® capsules. MINIPRESS® is indicated for the treatment of hypertension, to lower blood pressure.


US Patent number US 3511836, US3635979 and US3663706 discloses Prazosin (compound of formula II) and its acid addition salts.
The U.S. Patents US 3511836 and US3635979 specifically discloses prazosin compound of formula II and its acid addition salts and U.S. Pat. No. 3,663,706 discloses the use of the prazosin (Formula II) and its pharmaceutically acceptable acid addition salts as valuable hypotensive agents.
Scriabine et al., Experientia, 24, 1150(1968) discloses pharmacological studies on 2-[4-(2-furoyl)piperazin-l-yl]-4-amino-6,7-dimethoxyquinazo]ine hydrochloride, or prazosin hydrochloride. Preliminary clinical studies on prazosin hydrochloride were reported by Cohen, J. Clin. Pharmacol, 10, 408(1970).
US4092315 patent discloses polymorphic forms of Prazosin hydrochloride including crystalline a-form, p-form, y-form, monohydrate, dihydrate, polyhydrate, anhydrate, methanolate forms of Prazosin hydrochloride.
US4739055 patent discloses anhydrous, stable, crystalline 8-form of prazosin
hydrochloride
JP03206088 patent describes anhydrous epsilon type crystalline of Prazosin
hydrochloride.
IN4222/CHE/2015 patent application discloses crystalline form-M, form-N, Form-S of Prazosin hydrochloride and improved process for the preparation of Prazosin

hydrochloride using furan-2-yl(piperazin-l-yi)methanone oxalate (VI) as depicted in scheme below:

This method associate with preparation and isolation of oxalate salt of compound of formula VI, use of base and multistep synthesis procedure.
Thus there are only few literatures available for the preparation of Prazosin hydrochloride and available routes have many disadvantages such as tedious workup, costlier reagent, intermediate steps, isolation of intermediates, formation of impurities, use of hazardous reagents, solvents, and lower yield.
Accordingly there is need to develop a process of preparing prazosin hydrochloride compound of formula I, which is simple, economic, safe and industrially viable and providing the better yield and purity of the final prazosin hydrochloride.
Object of the invention:
An object of the invention is to provide a simple, economic, safe and industrially viable process for preparation of prazosin hydrochloride the compound represented by structural formula I:


Another object of the present invention is to provide a simple, economic, safe and industrially viable process for preparation of Prazosin represented by compound of Formula II:

It is further object of the present invention to provide a commercially viable process for the production prazosin hydrochloride.
Another object of present invention is to provide a process for preparation of prazosin hydrochloride (the compound represented by structural formula I) comprising
a) treating 2-chloro-6,7-dimethoxyquinazolin-4-amine (compound of formula VII) with furan-2-yl(piperazin-l-yl) methanone hydrochloride (compound of formula VIII) in solvent selected from 1,4-Dioxane, Sulfolane, Methyl isobutyl ketone (MIBK), n-butanol, N,N-Dimethylformamide, Dimethylsulfoxide, Water or any combination thereof,


In another object of present invention is to provide the process for preparation of prazosin hydrochloride (the compound represented by structural formula I) comprising:
a) treating 2-chloro-6,7-dimethoxyquinazolin-4-amine (compound of formula VII) with furan-2-yl(piperazin-l-yl) methanone hydrochloride (compound of formula VIII) in solvent selected from 1,4-Dioxane, Sulfolane, Methyl isobutyl ketone (MIBK), n-butanol, N,N-Dimethylformamide, Dimethylsulfoxide, Water or any combination thereof to give compound of formula (I),
b) optionally treating compound of formula I with dichloromethane (DCM); methanol & water and isolation of pure compound of formula (I),

In another object of present invention is to provide the process for preparation of prazosin hydrochloride (the compound represented by structural formula I) comprising:
a) treating 2-chloro-6,7-dimethoxyquinazolin-4-amine (compound of formula VII) with furan-2-yl(piperazin-l-yl) methanone hydrochloride (compound of

formula VIII) in absence of base in solvent selected from 1,4-Dioxane, Sulfolane, Methyl isobutyl ketone (MIBK), n-butanol, N,N-Dimethylformamide, Dimethylsulfoxide, Water or any combination thereof at temperature range of boiling point of solvent or at 100 to 125 °C to give compound of formula (I).
In another object of present invention is to provide the process for preparation of prazosin hydrochloride (the compound represented by structural formula I) comprising:
a) treating 2-chloro-6,7-dimethoxyquinazolin-4-amine (compound of formula
VII) with furan-2-yl(piperazin-l-yl) methanone hydrochloride (compound of
formula VIII) in absence of base in solvent selected from 1,4-Dioxane,
Sulfolane, Methyl isobutyl ketone (MIBK), n-butanol, N,N-
Dimethylformamide, Dimethylsulfoxide, Water or any combination thereof at
temperature range of boiling point of solvent or at 100 to 125 °C to give
compound of formula (I),
b) optionally treating compound of formula I with dichloromethane (DCM);
methanol & water and isolation of pure compound of formula (I).
In another object of present invention is to provide the process for preparation of prazosin (the compound represented by structural formula II) comprising steps of:
i) treating 2-chloro-6,7-dimethoxyquinazolin-4-amine (compound of formula VII) with furan-2-yl(piperazin-l-yl) methanone hydrochloride (compound of formula VIII) in solvent selected from 1,4-Dioxane, Sulfolane, Methyl isobutyl ketone (MIBK), n-butanol, N,N-Dimethylformamide, Dimethylsulfoxide, Water or any combination thereof,
ii) optionally converting compound of formula II to compound of formula (I),


In another object of present invention is to provide the process for preparation of prazosin (the compound represented by structural formula II) comprising:
i) treating 2-chloro-6,7-dimethoxyquinazolin-4-amine (compound of formula VII) with furan-2-yl(piperazin-l-yl) methanone (compound of formula V) in absence of base in solvent selected from 1,4-Dioxane, Sulfolane, Methyl isobutyl ketone (MIBK), n-butanol, N,N-Dimethylformamide, Dimethylsulfoxide, Water or any combination thereof at temperature range of boiling point of solvent or at 100 to 125 °C to give compound of formula (II).
Further object of the present invention is to provide a process for preparation of prazosin hydrochloride represented by compound of Formula I, Prazosin represented by compound of Formula II which avoids the yield loss due to purification of intermediate providing the compound represented by structural formula I with better yield and purity.
Summary of the invention:
In accordance with the aspect of the present invention is to provide a simple, economic, safe and industrially viable process for preparation of Prazosin hydrochloride the compound represented by structural formula I:


According to another aspect of the present invention provides is to provide, a process for preparation of Prazosin represented by compound of Formula II:

In another aspect of present invention, a process for preparation of prazosin hydrochloride (the compound represented by structural formula I) comprising:
b) treating 2-chloro-6,7-dimethoxyquinazolin-4-amine (compound of formula VII) with furan-2-yl(piperazin-l-yl) methanone hydrochloride (compound of formula VIII) in solvent selected from 1,4-Dioxane, Sulfolane, Methyl isobutyl ketone (MIBK), n-butanol, N,N-Dimethylformamide, Dimethylsulfoxide, Water or any combination thereof.
In another aspect of present invention is to provide, a process for preparation of prazosin hydrochloride (the compound represented by structural formula I) comprising:
a) treating 2-chloro-6,7-dimethoxyquinazolin-4-amine (compound of formula VII) with fliran-2-yl(piperazin-l-yl) methanone hydrochloride (compound of

formula VIII) in solvent selected from 1,4-Dioxane, Sulfolane, Methyl isobutyl ketone (MIBK), n-butatiol, N,N-Dimethylformamide, Dimethylsulfoxide, Water or any combination thereof to give compound of formula (I) b) optionally treating compound of formula I with dichloromethane (DCM); methanol & water and isolation of pure compound of formula (I).
In another aspect of present invention is to provide, a process for preparation of prazosin (the compound represented by structural formula II) comprising:
a) treating 2-chloro-6,7-dimethoxyquinazolin-4-amine (compound of formula VII) with furan-2-yl(piperazin-l-yl) methanone (compound of formula V) in absence of base in solvent selected from 1,4-Dioxane, Sulfolane, Methyl isobutyl ketone (MIBK), n-butanol, N,N-Dimethylformamide, Dimethylsulfoxide, Water or any combination thereof at temperature range of boiling point of solvent or at 100 to 125 °C to give compound of formula (II).
In another aspect of present invention is to provide, a process for preparation of prazosin (the compound represented by structural formula II) comprising steps of:
i) treating 2-chloro-6,7-dimethoxyquinazolin-4-amine (compound of formula VII) with furan-2-yl(piperazin-l-yl) methanone hydrochloride (compound of formula VIII) in solvent selected from 1,4-Dioxane, Sulfolane, Methyl isobutyl ketone (MIBK), n-butanol, N,N-Dimethylformamide, Dimethylsulfoxide, Water or any combination thereof,
ii) optionally converting compound of formula II to compound of formula (I).
In another aspect of present invention is to provide, a process for preparation of prazosin (the compound represented by structural formula II) comprising:
a) treating 2-chloro-6,7-dimethoxyquinazolin-4-amine (compound of formula VII) with furan-2-yl(piperazin-l-yl) methanone (compound of formula V) in absence of base in solvent selected from 1,4-Dioxane, Sulfolane, Methyl

isobutyl ketone (MIBK), n-butanol, N,N-Dimethylformamide, Dimethylsulfoxide, Water or any combination thereof at temperature range of boiling point of solvent or at 100 to 125 °C to give compound of formula (II).
Detail description of the invention:
The present invention relates to a simple, economic, safe and industrially viable process for preparation of prazosin hydrochloride the compound represented by structural formula I.
In an aspect of present invention, the process for preparation of prazosin hydrochloride (the compound represented by structural formula I) comprising:
a) treating 2-chloro-6,7-dimethoxyquinazolin-4-amine (compound of formula VII) with furan-2-yl(piperazin-l-yl) methanone hydrochloride (compound of formula VIII) in solvent selected from 1,4-Dioxane, Sulfolane, Methyl isobutyl ketone (MIBK), n-butanol, N,N-Dimethylformamide, Dimethylsulfoxide, Water or any combination thereof,

In another aspect of present invention, the process for preparation of prazosin hydrochloride (the compound represented by structural formula I) comprising:
a) treating 2-chloro-6,7-dimethoxyquinazolin-4-amine (compound of formula VII) with furan-2-yl(piperazin-l-yl) methanone hydrochloride (compound of formula VIII) in solvent selected from 1,4-Dioxane, Sulfolane, Methyl isobutyl ketone (MIBK), n-butanol, N,N-Dimethylformamide,

Dimethylsulfoxide, Water or any combination thereof to give compound of formula (I) b) optionally treating compound of formula I with dichloromethane (DCM); methanol & water and isolation of pure compound of formula (I),

In another aspect of present invention, the process for preparation of prazosin Hydrochloride (the compound represented by structural formula I) comprising steps of:

ii) converting compound of formula II to compound of formula (I).
i) treating 2-chloro-6,7-dimethoxyquinazolin-4-amine (compound of formula VII) with furan-2-yl(piperazin-l-yl) methanone hydrochloride (compound of formula V) in solvent selected from 1,4-Dioxane, Sulfolane, Methyl isobutyl ketone (MIBK), n-butanol, N,N-Dimethylformamide, Dimethylsulfoxide, Water or any combination thereof,

In another aspect of present invention, the process for preparation of prazosin (the compound represented by structural formula II) comprising steps of:
iii) treating 2-chloro-6,7-dimethoxyquinazolin-4-amine (compound of formula VII) with furan-2-yl(piperazin-l-yl) methanone hydrochloride (compound of formula V) in solvent selected from 1,4-Dioxane, Sulfolane, Methyl isobutyl ketone (MIBK), n-butanol, N,N-Dimethylformamide, Dimethylsulfoxide, Water or any combination thereof,

iv) optionally converting compound of formula II to compound of formula (I),
In an embodiment of the present invention, the process for preparation of prazosin hydrochloride (the compound represented by structural formula I) comprising: reaction of 2-chloro-6,7-dimethoxyquinazolin-4-amine (compound of formula VII) with furan-2-yl(piperazin-l-yl) methanone hydrochloride (compound of formula VIII) can be carried out in solvent selected from 1,4 dioxane, Sulfolane, Methyl isobutyl ketone (MIBK), n-butanol, or any combination thereof.
In another embodiment of the present invention, reaction of 2-chloro-6,7-dimethoxyquinazolin-4-amine (compound of formula VII) with furan-2-yl(piperazin-1-yl) methanone hydrochloride (compound of formula VIII) cab be carried out in solvent selected from 1,4-Dioxane, Sulfolane, Methyl isobutyl ketone (MIBK), n-butanol, N,N-Dimethylformamide, Dimethylsulfoxide, Water or any combination thereof at temperature range of boiling point of solvent or at 90 to 200 °C, preferably at 100 to 150 °C, more preferably at 100 to 125 °C.

In another embodiment of the present invention, reaction of 2-chloro-6,7-dimcthoxyquinazolin-4-amine (compound of formula VII) with furan-2-yl(piperazin-1-yl) methanone hydrochloride (compound of formula VIII) can be earned out in 1,4 dioxane, or Sulfolane at temperature range of boiling point of solvent or at 100 to 120 °C.
In another embodiment of the present invention, reaction of 2-chloro-6,7-dimethoxyquinazolin-4-amine (compound of formula VII) with furan-2-yl(piperazin-1-yl) methanone hydrochloride (compound of formula VIII) can be carried out in absence of base.
In another embodiment of the present invention, reaction of 2-chloro-6,7-dimethoxyquinazolin-4-amine (compound of formula VII) with furan-2-yl(piperazin-1-yl) methanone hydrochloride (compound of formula VIII) cab be carried out in absence of base in solvent selected from 1,4-Dioxane, Sulfolane, Methyl isobutyl ketone (MIBK), n-butanol, N,N-Dimethylformamide, Dimethylsulfoxide, Water or any combination thereof at temperature range of boiling point of solvent or at 90 to 200 °C, preferably at 100 to 150 °C, more preferably at 100 to 125 °C.
In another embodiment of the present invention, reaction of 2-chloro-6,7-dimethoxyquinazolin-4-amine (compound of formula VII) with furan-2-yl(piperazin-1-yl) methanone hydrochloride (compound of formula VIII) can be carried out in presence of base selected from triethyl amine or disopropyl ethyl amine.
In another embodiment of the present invention, conversion of of 2-chloro-6,7-dimethoxyquinazolin-4-amine (compound of formula VII) with furan-2-yl(piperazin-1-yl) methanone hydrochloride (compound of formula VIII) can be carried out in presence of base selected from tri ethyl amine or disopropyl ethyl amine.
In another embodiment of the present invention, the process for preparation of prazosin (the compound represented by structural formula II) comprising steps of

reaction of 2-chloro-6,7-dimethoxyquinazolin-4-amine (compound of formula VII) with furan-2-yl(piperazin-l-yl) methanone (compound of formula V) cab be carried out in solvent selected from 1,4-Dioxane, Sulfolane, Methyl isobutyl ketone (MIBK), n-butanol, N,N-Dimethylformamide, Dimethylsulfoxide, Water or any combination thereof at temperature range of boiling point of solvent or at 90 to 200 °C, preferably at 100 to 150 °C, more preferably at 100 to 125 °C.
In another embodiment of the present invention, reaction of 2-chloro-6,7-dimethoxyquinazolin-4-amine (compound of formula VII) with furan-2-yl(piperazin-1-yl) methanone (compound of formula V) can be carried out in 1,4-Dioxane, or Sulfolane at temperature range of boiling point of solvent or at 100 to 120 °C.
In another embodiment of the present invention, reaction of 2-chloro-6,7-dimethoxyquinazolin-4-amine (compound of formula VII) with furan-2-yl(piperazin-1-yl) methanone (compound of formula V) can be carried out in absence of base.
In another embodiment of the present invention, reaction of 2-chloro-6,7-dimethoxyquinazolin-4-amine (compound of formula VII) with furan-2-yl(piperazin-1-yl) methanone (compound of formula V) cab be carried out in absence of base in solvent selected from 1,4 dioxane, Sulfolane, Methyl isobutyl ketone (MIBK), n-butanol or any combination thereof at temperature range of boiling point of solvent or at 90 to 200 °C, preferably at 100 to 150 °C, more preferably at 100 to 125 °C.
In another embodiment of the present invention, reaction of 2-chloro-6,7-dimethoxyquinazolin-4-amine (compound of formula VII) with furan-2-yl(piperazin-1-yl) methanone (compound of formula V) can be carried out in presence of base selected from triethyl amine or disopropyl ethyl amine.
In another embodiment , compound of formula (II) converted to the compound of formula (I), by treating compound of structural formula (II) with alcoholic hydrochloride solution in above mentioned polar protic solvent for a period of 30 minutes to 6 hours to get compound of structural formula (I).

The examples of alcoholic hydrochloride solution may include methanolic hydrochloric acid, ethanolic hydrochloric acid or isopropanolic hydrochloric acid.
The alcoholic hydrochloride solution may contain hydrochloric acid in the range of 5% weight /weight to 30% weight / weight.
The compound of structural formula I or II may be isolated by the steps of filtration, centrifugation, washing, drying or the combinations thereof.
In another embodiment , compound of formula (V) converted to the compound of formula (VIII), by treating compound of structural formula (V) with alcoholic hydrochloride solution in above mentioned polar protic solvent for a period of 30 minutes to 6 hours to get compound of structural formula V. The examples of alcoholic hydrochloride solution may include methanolic hydrochloric acid, ethanolic hydrochloric acid or isopropanolic hydrochloric acid.
In another embodiment, compound of formula (VIII) converted to the compound of formula (V), by treating compound of structural formula (VIII) with base. The base is an inorganic base selected from ammonia, alkali metal hydroxides, carbonates and bicarbonates. Preferable alkali metal is sodium or potassium. Preferred base is aq. ammonia or triethyl amine or disopropyl ethyl amine.
In another embodiment, compound of formula (I) converted to the compound of formula (II), by treating compound of structural formula (I) with base. The base is an inorganic base selected from ammonia, alkali metal hydroxides, carbonates and bicarbonates. Preferable alkali metal is sodium or potassium. Preferred base is aq. ammonia or triethyl amine or disopropyl ethyl amine.

Example:
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 4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-l-yl]-(furan-2-yl)methanone hydrochloride (Prazosin Hydrochloride, Formula I) n-butanol (60ml), 2-chloro-6,7-dimethoxyquinazolin-4-amine (10.0g), and furan-2-yl(piperazin-l-yl) methanone hydrochloride were successively charged to a round bottom flask to get reaction mixture. The reaction mixture was stirred at 115 to 120°C for 2 to 3 hours. After completion of reaction, as monitored by TLC; the reaction mixture was quenched with water (60ml). Solid mass filtered, washed with water and dried under vacuum to obtain 16.0g of title compound.
Example 2: Preparation of 4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-l-yl]-(furan-2-yl)methanone hydrochloride (Prazosin Hydrochloride, Formula I) N,N-dimethylformamide (60ml), 2-chloro-6,7-dimethoxyquinazolin-4-amine (10.0g), and furan-2-yl(piperazin-l-yl) methanone hydrochloride were successively charged to a round bottom flask to get reaction mixture. The reaction mixture was stirred at 115 to 120°C for 2 to 2.5 hours. After completion of reaction, as monitored by TLC; the reaction mixture was quenched with water (60ml). Solid mass filtered, washed with water and dried under vacuum to obtain 15.5g of title compound.
Example 3: Preparation of 4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-l-yl]-(furan-2-yl)methanone hydrochloride (Prazosin Hydrochloride, Formula I) Sulfolane (60ml), 2-chloro-6,7-dimethoxyquinazolin-4-amine (10.0g), and furan-2-yl(piperazin-l-yl) methanone hydrochloride were successively charged to a round bottom flask to get reaction mixture. The reaction mixture was stirred at 115 to

120°C for 20 to 24 hours. After completion of reaction, the reaction mixture was quenched with water (60ml). Solid mass filtered, washed with water and dried under vacuum to obtain 14.0g of title compound.
Example 4: Preparation of 4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-l-yl]-(furan-2-yl)methanone hydrochloride (Prazosin Hydrochloride, Formula I) 1-4 Dioxane (60ml), 2-chloro-6,7-dimethoxyquinazolin-4-amine (lO.Og), and furan-2-yl(piperazin-l-yl) methanone hydrochloride were successively charged to a round bottom flask to get reaction mixture. The reaction mixture was stirred at 100 to 105°C for 30 to 32 hours. After completion of reaction, the reaction mixture was quenched with water (60ml). Solid mass filtered, washed with water and dried under vacuum to obtain 12.5g of title compound.
Example 5: Preparation of 4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-l-yl]-(furan-2-yl)methanone hydrochloride (Prazosin Hydrochloride, Formula I) Dimethylsulfoxide (60ml), 2-chloro-6,7-dimethoxyquinazolin-4-amine (10.0g), and furan-2-yl(piperazin-l-yl) methanone hydrochloride were successively charged to a round bottom flask to get reaction mixture. The reaction mixture was stirred at 115 to 120°C for 3 to 4 hours. After completion of reaction, the reaction mixture was quenched with water (60ml). Solid mass filtered, washed with water and dried under vacuum to obtain 10.8g of title compound.
Example 6: Preparation of 4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-l-yl]-(furan-2-yl)methanone hydrochloride (Prazosin Hydrochloride, Formula I) Methyl isobutyl ketone (60ml), 2-chloro-6,7-dimethoxyquinazolin-4-amine (10.0g), and furan-2-yl(piperazin-l-yl) methanone hydrochloride were successively charged to a round bottom flask to get reaction mixture. The reaction mixture was stirred at 105 to 110°C for 22 to 24 hours. After completion of reaction, the reaction mixture

was quenched with water (60ml). Solid mass filtered, washed with water and dried under vacuum to obtain 14.5g of title compound.
Example 7: Preparation of 4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-l-yl]-(furan-2-yl)methanone hydrochloride (Prazosin Hydrochloride, Formula I) Dimethylsulfoxide (60ml), Water (40ml), 2-chloro-6,7-dimethoxyquinazolin-4-amine (10.0g), and furan-2-yl(piperazin-l-yl) methanone hydrochloride were successively charged to a round bottom flask to get reaction mixture. The reaction mixture was stirred at 115 to 120°C for 3 to 4 hours. After completion of reaction, the reaction mixture was quenched with water (60ml). Solid mass filtered, washed with water and dried under vacuum to obtain 15.0g of title compound.
Example 8: Preparation of 4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-l-yl]-(furan-2-yl)methanone hydrochloride (Prazosin Hydrochloride, Formula I) Water (60ml), 2-chloro-6,7-dimethoxyquinazolin-4-amine (10.0g), and furan-2-yl(piperazin-l-yl) methanone hydrochloride were successively charged to a round bottom flask to get reaction mixture. The reaction mixture was stirred at 100 to 105°C for 20 to 24 hours. After completion of reaction, the reaction mixture was quenched with water (60ml). Solid mass filtered, washed with water and dried under vacuum to obtain 13.5g of title compound.
Example 9: Preparation of 4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-l-yl]-(furan-2-yl)methanone hydrochloride (Prazosin Hydrochloride, Formula I) N,N-Dimethylformamide (60ml), 2-chloro-6,7-dimethoxyquinazolin-4-amine (10.Og), furan-2-yl(piperazin-1 -yl) methanone hydrochloride and triethylamine (4.43g) were successively charged to a round bottom flask to get reaction mixture. The reaction mixture was stirred at 115 to 120°C for 2 to 2.5 hours. After completion of reaction, as monitored by TLC; the reaction mixture was quenched with water

(60ml). Solid mass filtered, washed with water and dried under vacuum to obtain 15.8g of title compound.
Example 10: Preparation of 4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-l-yl]-(furan-2-yl)methanone hydrochloride
Sulfolane (60ml), 2-chloro-6,7-dimethoxyquinazolin-4-amine (10.0g), furan-2-yl(piperazin-l-yl) methanone hydrochloride and triethylamine (4.43 g) were successively charged to a round bottom flask to get reaction mixture. The reaction mixture was stirred at 115 to 120°C for 3 to 4 hours. After completion of reaction, as monitored by TLC; the reaction mixture was quenched with water (60ml). Solid mass filtered, washed with water and dried under vacuum to obtain 15.0g of title compound.
Example 11: Preparation of 4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-l-yl]-(furan-2-yl)methanone (Prazosin Hydrochloride, Formula I) 1,4-Dioxane (60ml), 2-chloro-6,7-dimethoxyquinazolin-4-amine (10.0g), furan-2-yl(piperazin-1 -yl) methanone hydrochloride and triethylamine (4.43 g) were successively charged to a round bottom flask to get reaction mixture. The reaction mixture was stirred at 100 to 105°C for 3 to 4 hours. After completion of reaction, the reaction mixture was quenched with water (60ml). Solid mass filtered, washed with water and dried under vacuum to obtain 15.4g of title compound.
Example 12: Preparation of 4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-l-yl]-(fiiran-2-yl)methanone hydrochloride
Dimethylsulfoxide (60ml), 2-chloro-6,7-dimethoxyquinazolin-4-amine (10.0g), furan-2-yl(piperazin-l-yl) methanone hydrochloride and triethylamine (4.43g) were successively charged to a round bottom flask to get reaction mixture. The reaction mixture was stirred at 115 to 120°C for 2 to 3 hours. After completion of reaction,

the reaction mixture was quenched with water (60ml). Solid mass filtered, washed with water and dried under vacuum to obtain 14.0g of title compound.
Example 13: Preparation of 4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-l-yl]-(furan-2-yl)methanone hydrochloride
Methyl isobutyl ketone (60ml), 2-chloro-6,7-dimethoxyquinazolin-4-amine (10.0g), furan-2-yl(piperazin-l-yl) methanone hydrochloride and triethylamine (4.43g) were successively charged to a round bottom flask to get reaction mixture. The reaction mixture was stirred at 105 to 110°C for 3 to 4 hours. After completion of reaction, the reaction mixture was quenched with water (60ml). Solid mass filtered, washed with water and dried under vacuum to obtain 15.0g of title compound.
Example 14: Preparation of 4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-l-yl]-(furan-2-yl)methanone hydrochloride
Dimethylsulfoxide (30ml), Water (30ml), 2-chloro-6,7-dimethoxyquinazolin-4-amine (10.0g), and furan-2-yl(piperazin-1 -yl) methanone hydrochloride and triethylamine (4.43g) were successively charged to a round bottom flask to get reaction mixture. The reaction mixture was stirred at 115 to 120°C for 3 to 4 hours. After completion of reaction, the reaction mixture was quenched with water (60ml). Solid mass filtered, washed with water and dried under vacuum to obtain 15.5g of title compound.
Example 15: Preparation of 4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-(furan-2-yl)methanone hydrochloride
Water (60ml), 2-chloro-6,7-dimethoxyquinazolin-4-amine (10.Og), furan-2-yl(piperazin-1 -yl) methanone hydrochloride and triethylamine (4.43 g) were successively charged to a round bottom flask to get reaction mixture. The reaction mixture was stirred at 100 to 105°C for 12 to 14 hours. After completion of reaction,

the reaction mixture was quenched with water (60ml). Solid mass filtered, washed with water and dried under vacuum.

We Claim:
1. A process for preparation of prazosin hydrochloride (the compound represented by
structural formula I) comprising:
a) treating 2-chloro-6,7-dimethoxyquinazolin-4-amine (compound of formula VII) with furan-2-yl(piperazin-l-yl) methanone hydrochloride (compound of formula VIII) in solvent selected from 1,4-Dioxane, Sulfolane, Methyl isobutyl ketone (MIBK), n-butanol, N,N-Dimethylformamide, Dimethylsulfoxide, Water or any combination thereof,

2. A process for preparation of prazosin Hydrochloride (the compound represented by
structural formula I) comprising steps of:
ii) converting compound of formula II to compound of formula (I).
i) treating 2-chloro-6,7-dimethoxyquinazolin-4-amine (compound of formula VII) with furan-2-yl(piperazin-l-yl) methanone hydrochloride (compound of formula V) in solvent selected from 1,4-Dioxane, Sulfolane, Methyl isobutyl ketone (MIBK), n-butanol, N,N-Dimethylformamide, Dimethylsulfoxide, Water or any combination thereof,


3. A process for preparation of prazosin (the compound represented by structural
formula II) comprising steps of:
i) treating 2-chloro-6,7-dimethoxyquinazolin-4-amine (compound of formula VII) with furan-2-yl(piperazin-l-yl) methanone hydrochloride (compound of formula VIII) in solvent selected from 1,4-Dioxane, Sulfolane, Methyl isobutyl ketone (MIBK), n-butanol, N,N-Dimethylformamide, Dimethylsulfoxide, Water or any combination thereof, ii) optionally converting compound of formula II to compound of formula (I).
4. The process for preparation of prazosin as claimed in claim 3 comprising:
a) treating 2-chloro-6,7-dimethoxyquinazolin-4-amine (compound of formula VII) with furan-2-yl(piperazin-l-yl) methanone (compound of formula V) in absence of base in solvent selected from 1,4-Dioxane, Sulfolane, Methyl isobutyl ketone (MIBK), n-butanol, N,N-Dimethylformamide, Dimethylsulfoxide, Water or any combination thereof at temperature range of boiling point of solvent or at 100 to 125 °C to give compound of formula (II).
5. The process as claimed in claim 1, 2, 3 or 4, wherein the process is carried out in absence of base or presence of base selected from triethyl amine or disopropyl ethyl amine.
6. The process as claimed in claim 2 to 5, wherein the compound of formula (II) converted to the compound of formula (I), by treating compound of structural formula (II) with alcoholic hydrochloride solution in above mentioned polar protic solvent for a period of 30 minutes to 6 hours to get compound of structural formula (I).

7. A process for preparation of prazosin (the compound represented by structural formula II) comprising steps of:

i) treating 2-chloro-6,7-dimethoxyquinazolin-4-amine (compound of formula VII) with furan-2-yl(piperazin-l-yl) methanone (compound of formula V) in solvent selected from 1,4-Dioxane, Sulfolane, Methyl isobutyl ketone (MIBK), n-butanol, N,N-Dimethylformamide, Dimethylsulfoxide, Water or any combination thereof, ii) optionally converting compound of formula II to compound of formula (I).
8. The process as claimed in claim 7, wherein preparation of prazosin (the compound
represented by structural formula II) comprising:
a) treating 2-chloro-6,7-dimethoxyquinazolin-4-amine (compound of formula VII) with furan-2-yl(piperazin-l-yl) methanone (compound of formula V) in absence of base in solvent selected from 1,4-Dioxane, Sulfolane, Methyl isobutyl ketone (MIBK), n-butanol, N,N-Dimethylformamide, Dimethylsulfoxide, Water or any combination thereof at temperature range of boiling point of solvent or at 100 to 125 °C to give compound of formula (II).
9. The process as claimed in claim 7, wherein the process is carried out in absence or
base or presence of base selected from triethyl amine or disopropyl ethyl amine.
10. The process as claimed in claims 6-9, wherein compound of formula (II)
converted to the compound of formula (I), by treating compound of structural formula

(II) with alcoholic hydrochloride solution in above mentioned polar protic solvent for a period of 30 minutes to 6 hours to get compound of structural formula (I).