FIELD OF THE INVENTION:
An advantageous process for preparing 6,7-dimethoxy-2-(piperazin-l-yl)quinazolin-4-amine BACKGROUND OF THE INVENTION:
Doxazosin, quinazoline compound, is chemically known as 4-amino-2-[4-(l,4-benzodioxan-2-carbonyl)piperazin-l-yl]-6,7-dimethoxyquinazoline of formula I.
Doxazosin is used as antihypertensive drug and marketed under trademarks in Italy and the United States CARDURA®, under form salified with the methanesulfonic acid named doxazosin mesylate.
US 4188390 discloses doxazosin and its pharmaceuticalty acceptable salts. It also describes the process of preparation thereof. The doxazosin HC1 is prepared by reacting 4-amino-2chloro-6,7-dimethoxy quinazoline with N-(I,4-benzodioxan-2-carbonyl)piperazine as represented in following reaction scheme-1.
Present invention discloses process for preparing 6,7-dimethoxy-2-(piperazin-l-yl)quinazolin-4-amine of formula-2 which is key intermediate for preparing Doxazosin.

FormuIa-2
There are very few references for the synthesis of 6,7-dimethoxy-2-(piperazin-l-
yl)quinazo!in-4-amine.
US 3,511,836 discloses various 2,4-substituted-6,7-dimethoxyquinazoIine compounds. Us
3,511,836 also discloses several processes for the preparation of 2-(4-substituted)piperazin-l-
yl)4-amino-6,7-dimethoxyquinazoline.
Us 3,663,706 describes process for preparing 2-(4-methy-l-piperazinyl)-4-amino-6,7-
dimethoxy quinazoline comprises reaction of .2-chloro-4-amino-6,7-dimethoxyquinazoline
with 4-methyl piperazine in presence of ethanol and recrystallised from methanol/water.
US 4,483,857 and US 4,734,418 discloses procedures for the synthesis of derivatives with
structure similar to 6,7-dimethoxy-2-(piperazin-l-yl)quinazolin-4-amine.
Pharm.Sci.Asia 2018,45(2),77-92 discloses the synthesis of 6,7-dimethoxy-2-(piperazin-l-
yl)quinazolin-4-amine which comprises reaction of 2-chloro-4-amino-6,7-
dimethoxyquinazoline with piperazin in presence of isoamyl alcohol.
The present invention provides a robust, ecofriendly, commercially viable process for preparing 6,7-dimethoxy-2-(piperazin-l-yl)quinazoIin-4-amine.
SUMMARY OF THE INVENTION:
The present invention relates to advantageous, safe and robust process for preparing 6,7-dimethoxy-2-(piperazin-l-yl)quinazolin-4-amine of formula-2
Formula-2
One embodiment of the present invention provides a process for preparing 6.7-dimethoxy-2-(piperazin-l-yl)quinazolin-4-amine of formula-2 comprising the steps of;

(a) Reacting 2-chloro-4amino-6,7-dimethoxy quinazoline with piperazine in presence of base and water
(b) Isolating 6,7-dimethoxy-2-(piperazin-l-yl)quinazolin-4-amine
DETAIL DESCRIPTION OF THE INVENTION:
The present invention relates to improved, economical and industrially applicable process for the preparation of 6,7-dimethoxy-2-(piperazin-l-yl)quinazolin-4-amine of formula-2
Formula-2
One aspect of the present invention provides a process for preparing 6,7-dimethoxy-2-(piperazin-l-yl)quinazolin-4-amine of formula-2 comprising the steps of;
(a) Reacting 2-chloro-4amino-6,7-dimethoxy quinazoline with piperazine in presence of base and water
(b) Isolating 6,7-dimethoxy-2-(piperazin-1 -yl)quinazolin-4-amine
The process for preparation of 6,7-dimethoxy-2-(piperazin-l-yl)quinazolin-4-amine of. formula-2 is depicted in the following reaction scheme-2
Scheme-2
The base used in step (a) is inorganic base. The inorganic base is selected from hydroxides like sodium hydroxide, potassium hydroxide, lithium hydroxide, carbonate salts of alkali and alkaline earth metals like potassium carbonate, potassium bicarbonate, sodium carbonate, sodium bicarbonate, cesium carbonate.

The present invention avoids the use of costly and hazardous solvents, which makes the present invention economical.
Moreover prior art process stated that the synthesis carried out at refluxed temperature i.e. 120°C and at temperature of more than 125°C, piperazine was decomposed and the reaction mixture became black brown. While in present invention synthesis carried out tempereature is85-100°C.
Moreover mother liquor of the product can be reused and recycled upto 4 cycles with top up. required piperazine mole.This makes the process non hazardous, more efficient and energy saving.
The present invention process for producing 6,7-dimethoxy-2-(piperazin-l-yI)quinazolin-4-amine approaching to green chemistry having excellent workability without using solvent.
The following examples explain various other embodiments without limiting the scope of the present invention.
Example-1: Preparation of 6,7-dimethoxy-2-(piperazin-l-yl)quinazolin-4-amine
lOOg (0.4172 mol) 2-chloro-4-amino-6,7-dimethoxy quinazoline and 360g (4.1792 mol) dissolved in 500ml of water and stirred for 6 hr at 85-100°C. The resulting reaction mixture was cooled to below 40 °C. 47.6g (0.85 mol) potassium hydroxide in 500ml water was added and stirred. The product was collected by filtration and dried to obtain 6,7-dimethoxy-2-(piperazin-l-yl)quinazolin-4-amine. Purity: 99.6%