The present invention relates to an improved process for preparing kinetin.

Kinetin is a kind of cytokinin, which promotes cell division. Recent studies revealed the prominent role of Kinetin in anti-aging effects, thereby drawing attention of Cosmetic Industry. The present invention is directed to a novel, facile synthesis of Kinetin, which has the advantage of Industrial applicability. Kinetin is represented by the formula

BACKGROUND OF THE INVENTION

Kinetin also known as 6-furfurylamino purine is a kind of cytokinin, a class of plant hormone, which promotes cell division. Kinetin reportedly promotes cell division of mammalian cells and is used as an ingredient in cosmetics for the same property. Since, 1994 Kinetin has been thoroughly tested for its anti-aging effects in human skin cells and other systems. Kinetin may be used in conjunction with other cell growth- or cell division-promoting compounds. For example, French Patent 1,587,633 (27 Mar. 1970) describes a method for preparing a plant extract that is enriched in kinetin. This French Patent suggests that, because the rate of cell renewal diminishes with age, the plant extract may be used in a cosmetic formulation for the treatment of sagging skin and wrinkles by increasing the rate of cell proliferation. Japanese patent Application Publication No. 60-19709 (1985) describes a composition that contains no more than 1 % of kinetin and no more than 20% of an uncharacterized lithosperum root extract and is said to accelerate cell division in human skin and thereby prevent skin-aging. As a signaling molecule, kinetin may stimulate other defense pathways such as DNA repair and proteosome mediated protein turnover. The usefulness of Kinetin as a nutritional supplement in stimulating the maintenance and repair pathways in the body, and as a general molecule of defence and a component of the homeodynamic machinery also need to be explored thoroughly.

Kinetin was originally isolated by Miller and Skoog as a compound from autoclaved herring sperm DNA that had cell division-promoting activity. It was given the name kinetin because of its ability to induce cell division, provided that auxin was present in the medium. The story of the discovery of kinetin is a fascinating example of the twists and turns of scientific discovery. Kinetin is often used in plant tissue culture for inducing formation of callus (in conjunction with auxin) and to regenerate shoot tissues from callus (with lower auxin concentration).

For a long time, it was believed that kinetin was an artifact produced from the deoxyadenosine residues in DNA, which degrade on standing for long periods or when heated during the isolation procedure.

Therefore, it was thought that kinetin does not occur naturally, but, since 1996, it has been shown by several researchers that kinetin exists naturally in the DNA of cells of almost all organisms tested so far, including human and various plants. The mechanism of production of kinetin in DNA is thought to be via the production of furfural — an oxidative damage product of deoxyribose sugar in DNA — and its quenching by the adenine base's converting it into N6-furfuryladenine, kinetin.
Since 1994, kinetin has been thoroughly tested for its powerful anti-aging effects in human skin cells and other systems. At present, kinetin is one of the widely used components in numerous skin care cosmetics and cosmeceuticals, such as Valeant products kineras. There are some reports published on other biological effects of kinetin in human beings, for example its effects as anti-platelet aggregation factor reducing thrombosis formation. In addition, it has been shown to be capable of correcting RNA mis-splicing in the disease of familial dysautonomia, in which exon 20 of IKBKAP is skipped instead of included in the disease, leading to insufficient levels of IKBKAP protein product as a result of frame-shift-induced nonsense-mediated decay.

Due to its beneficial effects, Kinetin has been studied extensively for its use in cosmetics and has become a widely used component in numerous skin care cosmetics and cosmeceuticals. In Several skin care products and potential cosmetic formulations containing Kinetin are being developed and sold (J. Anti-Ageing Med. 5, 2002, 113).

Various trials conducted recently have further demonstrated the anti-aging effects of topical kinetin. For eg., Chiu PC et al, in a randomized, double blind, placebo controlled trial, studied the anti-aging effect of topical Kinetin and Niacinamide in Asians (J CosmetDermato,20076(4):243-9).

DETAILED DESCRIPTION OF THE INVENTION

Cytokinins are N6-substituted adenine derivative. The furfuryl moiety of kinetin is reported to originate from furfural a primary oxidation product of deoxyribose in DNA (Biochem, biophys research column 1997,238,317). The biosynthetic pathway of kinetin involves the formation of furfural during hydroxyl radical oxidation of deoxyribose in DNA, its reaction with exocyclic amino groups of adenine residues followed by dehydration and reduction of the intermediate to N6-furfuryladenine (Febbs let, 1997 414,457).

PRIOR ART

Kinetin was known to be synthesized by the reaction between 6-chloropurine & Furfuryl amine in methyl cellosolve. (JACS, 1956, 78, 3693). 6-chloropurine employed in the said process is a commercial sample, and it being a very labile compound undergoes decomposition during its purification, thus reducing its yield and the final yield of Kinetin.

Another process in the prior art involves the synthesis of Kinetin from 4:5 diamino-6-furfuryl amino pyrimidine, ethyl orthoformate and acetic anhydride. (JCS, 1958, 2746).Acetic anhydride handling at an industrial scale is relatively less convenient.

Yet another recent known process describes the one pot synthesis of kinetin from hypoxanthine in 90 % yield (Org Lett; 2006, 8(11), 2425). However, there is a drastic reduction in the yield when the process was scaled up to kilogram level. Also highly expensive, BOP reagent is not suitable for industrial production of Kinetin.

Thus, it has been long felt need to develop process, which is cheaper and industrial friendly in nature.

Thus, there is immediate need for a novel synthesis which best suits to industry requirement.

Therefore the object of the present invention is to provide an industrially viable synthesis involving reagents which can be handled with ease and which results in considerably high yields of Kinetin. The process of present invention achieves these other objects:
According to present invention there is provided an improved process for preparing kinetin of formula from 6-chloro purine of formula

which comprises forming 6-hydroxy purine of formula by a process which consists of forming

a. 2-Mercapto-4-hydroxy-6-aminopyrimidine from which again forming
b. 2-Mercapto-4-hydroxy-5-nitroso-6-aminopyrimidine from which again forming
c. 2-Mercapto-4-hydroxy-5,6-diaminopyrimidine from which again forming
d. 5,6-Diamino-4-hydroxypyrimidine from which again forming
e. 4-Hydroxy-5,6-diaminopyrimidine-2-sulfinic acid from which again forming
f. 5,6-Diamino-4-hydroxypyrimidine from which again forming
g. 6-Hydroxypurine from which again forming
h. 2-Mercapto-6-hydroxypurine from which again forming i. 6-Chloropurine from which again finally forming j. 6-Furfuryl aminopurine (Kinetin) by method/s such as herein described.

One of the objects of the present invention is the synthesis of 6-chloropurine, which is (i) Scalable (ii) reproducible from a gram level to Kg level (iii) can be synthesized with ease (iv) yields an analytically pure compound which does not need further purification, thereby getting a relatively pure Kinetin as final product in a high yield.

Another object of the present invention is to synthesize Kinetin from the 6-hloropurinewhich in turn is synthesized in a relatively pure form and in high yields.
The synthetic process used in the current invention is depicted in Scheme I.

Modification in oxidation and desulfurization reaction conditions led to economically viable process for putative intermediate 5,6-diamino-4-hydroxypyrimidine.

SCHEME I

In one embodiment of the invention, 5, 6-diamino-4-hydroxypyrimidine and triethylorthoformate are taken in a suitable solvent and reacted at reflux to generate 6-hydroxypurine. The reaction can be conveniently carried out in solvents like Dimethyl formamide, Dimethyl sulfoxide, Dimethyl acetamide or the like.

The 6-hydroxy purine thus generated is treated with POCI3 in the presence of N.Niethyl, dimethyl, t-butyl aniline to generate 6-chloropurine. The 6-chloropurine thus prepared is considerably pure and can be used directly for the preparation of Kinetin.

In another embodiment of the invention, the 6-chloropurine prepared above is condensed with Furfuryl amine in a suitable solvent to yield Kinetin. The reaction can be conveniently carried out in solvents like Dimethyl formamide, Dimethyl acetamide, Dimethyl sulfoxide, Sulfones or the like. The reaction is carried out at temperatures above 75D C. The reaction is preferably carried out in Dimethyl sulfoxide and the most preferred temperature is 80-85°C. The yields of the reaction are greater than 95% even after industrial scale-up. The kinetin thus obtained can be recrystallized in water: acetic acid (1:1 v/v) to yield analytically pure crystalline compound.

In yet another embodiment, in stage 4 oxidation of the mercapto group is carried out in alkaline solution with hydrogen peroxide to sulfinic acid followed by decomposition with hydrochloric acid. The bases employed are sodium hydroxide, potassium hydroxide or the like.

In a preferred embodiment about 2 to 3 molecular proportion of sodium hydroxide was added followed by 1 to 1.5 molecular proportion of hydrogen peroxide per molecular proportion of 2- mercapto-4-hydroxy-5,6-diamino pyrimidine at a rate to provide temperature of the reaction mixture 0-3°C. The pH is adjusted to 4 and the precipitated solid filtered and dried. The oxidized compound was decomposed using methanolic hydrochloric acid.

In another embodiment, in stage 4, 2-mercapto-4-hydroxy-5,6-diaminopyrimidine was cyclised to 2-mercapto-6-hydroxy pyrimidine which on desulfurization using Raney Nickel yielded 6-hydroxy purine.

In yet another embodiment, in stage 7, 6-chloro purine in dimethyl sulfoxide was heated to reflux with furfuryl amine. In preferred embodiment, about 3-4 molecular proportion of furfuryl amine and 5 to 6 molecular proportion of dimethyl sulfoxide per molecular proportion of 6-chloro purine was heated at80-85°C for 7 hrs. The mixture was cooled to ambient temperature and washed with DM water followed by methanol and subsequently recrystallized in water: acetic acid (1:1 v/v) to yield analytically pure 6-furfurylaminopurine (Kinetin).

The invention is exemplified in the following examples, which are given by way of an illustration but does not restrict the scope of the invention.

EXAMPLE 1

Preparation of 2-Mercapto-4-hydroxy-6-aminopyrimidine:-

To a solution of methanol (1500 ml) and sodium metal (100g, 4.54mole), cyano acetic
acid ethyl ester, (250g, 2.21 mole) and thiourea(166g, 2.18 mole) were added. The reaction mixture was maintained at ambient temperature for about 90 minutes, followed by vigorous refluxing for a period of 2 hrs. The contents were subsequently cooled to 10°C & filtered. The wet sodium salt cake obtained was dissolved in DM water (1000 ml) at 10°C under stirring and made acidic with acetic acid to pH ~ 3. The precipitated crystals were filtered and the filter cake washed with DM water (500 ml), to yield 300 g (90%) of 2-mercapto-4-hydroxy-6-aminopyrimidine. mp: >300°C.

EXAMPLE 2

Preparation of 2-Mercapto-4-hydroxy-5-nitroso-6-aminopyrimidine:-

To a mixture of 2-mercapto-4-hydroxy-6-amino-pyrimidine (250 g, 1.74 mole) in acetic acid (2500 g, 41.6 mole) and DM water (500 ml), sodium nitrite (125 g, 1.81 mole) was added portion wise (2 hrs at ambient temperature). The reaction mixture was further maintained for 3 hrs. The wet cake after filtration was washed with DM water (500 ml) and methanol (500 ml) and dried to yield 2-mercapto-4-hydroxy-5-nitroso-6- aminopyrimidine 270 g (90%),mp: >300°C.

EXAMPLE 3

Preparation of 2-Mercapto-4-hydroxy-5,6-diaminopyrimidine:-

2-Mercapto-4-hydroxy-5-nitroso-6-aminopyrimidine (300 g, 1.74 mole) in DM water (3000 ml) was heated to 45-50°C under stirring, and sodium dithionite monohydrate (900 g, 5.1 mole) was added portion wise over a period of 2 hrs. The reaction was further maintained for 3 hrs at 50-55°C, and subsequently cooled to 10°Cand filtered. The wet cake was washed with DM water (500 ml), followed by methanol (500 ml), on drying 2-mercapto-4-hydroxy-5,6-diaminopyrimidine was obtained in a yield of 250 g, (90%).mp: >300°C.

EXAMPLE 4

Preparation of 2-Mercapto-4-hydroxy-5,6-diaminopyrimidine:

To a mixture of 2-mercapto-4-hydroxy-5,6-diamino pyrimidine (5g, 0.031 mole) in DM water (50ml), hydrochloric acid (1:1, v/v 20ml) was added at 40-45X and pH of the solution was adjusted to 5-6. Zinc dust (9g, 0.13 mole) was added to the reaction mixture over a period of 30 min, while adding the hydrochloric acid to maintain the pH 5-6. After addition of Zinc dust was completed, reaction mixture was stirred at 40-45°C for 1 hr. Concentrated hydrochloric acid (5ml) was added to lower the pH to 2-3 and filtered. The mother liquor was cooled to 20°C and cone, sulfuric acid (3g, 0.032 mole) was added and cooled to 5-10°C. The precipitate was filtered and washed with DM water (10ml) and dried, which gave 7g of the solid. This solid suspended in DM water (10ml) and cooled to 10°C and pH of the mixture was adjusted to 7-8, filtered and dried to yield 4g (88%) of 2-mercapto-4-hydroxy-5,6-diamino pyrimidine identical in all respects with a sample obtained from reduction of 2-mercapto-4-hydroxy-5-nitroso-6-amino pyrimidine using sodium dithionite.

EXAMPLE 5

Preparation of 5,6-Diamino-4-hydroxypyrimidine:-

To a solution of 2-mercapto-4-hydroxy-5,6-diamino-pyrimidine (100 g, 0.632 mole) in DM water (1500 ml) and liquor ammonia (25%, 135 g, 7.9 mole), Raney nickel (150 g)
was added. The reaction mixture was heated to reflux at 100°C and maintained for a period of 5 hrs, followed by hot filtration (80°C) and water wash (500ml). The mother
liquor was concentrated to dryness under vacuum, and the residue treated with methanol (400 ml) at 10°C. The reaction contents were acidified with IPA HCI (125 ml) to pH ~ 3, and further maintained at 10°C for 30 min, followed by filtration and methanol washing (100 ml) to yield 5,6-diamino-4-hydroxypyrimidine 75 g (88%), m: 250-252°C.

EXAMPLE 6

Preparation of 4-Hydroxy-5,6-diaminopyrimidine-2-sulfinic acid:-

To a pre-cooled solution (-3°C) of 2-mercapto-4-hydroxy-5,6-diaminopyrimidine (250g,
1.58 mole) in DM water (3700ml) containing sodium hydroxide (150g), was added dropwise, mixture of hydrogen peroxide (30%, 250ml,2.6 mole) and DM water (600ml)
for aperiod of 2-3 hrs. During the addition, the temperature was carefully maintained 0-
3°C. The reaction mixture was stirred at 0°C for 3 hrs and acidified with glacial acetic
acid to pH 4 at 0-5°C. The precipitated solid filtered washed with DM water (200ml) and
methanol (200ml), and dried to yield 260 g (86%) of 4-hydroxy-5,6-diaminopyrimidine-2-
sulfinilic acid.

EXAMPLE 7

Preparation of 5,6-Diamino-4-hydroxypyrimidine:-

A mixture of 4-hydroxy-5,6-diamino pyrimidine-2-sulfinic acid (100g, 0.52 mole) and methanol (2000ml) containing dry HCIgas (230g) was stirred at ambient temperature for 20 hrs. The reaction mixture was filtered and washed with methanol (100ml), and dried
to yield 75g (89%) of 5,6-diamino 4-hydroxy pyrimidine hydrochloride, identical in all
respects with an sample obtained from desulfurization of 2-mercapto-4-hydroxy-5,6-diaminopyrimidine using Raney nickel.

EXAMPLE 8

Preparation of 6-Hydroxypurine:-

A mixture of 5,6-diamino-4-hydroxypyrimidine (100 g, 0.79 mole) and
triethylorthoformate (445 g, 3 mole) in Dimethyl formamide (1000 ml) was stirred and
heated to reflux for a period of 6 hrs. The reaction mixture was subsequently cooled to
10°C and filtered. The wet cake was washed with methanol (100 ml), and dried to yield
85 g (84%) of 6-hydroxypurine.mp: >300°C.

EXAMPLE 9

Preparation of 2-Mercapto-6-hydroxypurine:-

A mixture of 5-6-diamino-4-hydroxy pyrimidine (5g, 0.031 mole) and triethylorthoformate (22.0g, 0.15 mole) in dimethyl formamide (35ml) was stirred, heated to reflux for a period of 6 hrs. The reaction mixture was subsequently cooled to 10°C and filtered. The wet cake was washed with methanol (10ml) and dried to yield 4.5 g (85%) of 2-mercapto-6-hydroxy purine.

EXAMPLE 10

Preparation of 6-Hydroxypurine:-

To a solution of 2-mercapto-6-hydroxy purine (2.5g, 0.015 mole) in DM water (40ml) and liquor ammonia (15ml, 25%)Raney nickel (3g) was added. The reaction mixture was heated to reflux at 100°C and maintained for a period of 3 hrs followed by hot filtration and water wash (20ml). The mother liquor was concentrated to dryness in vacuum and residue treated with methanol to yield 1.7 g (83 %) of 6-hydroxypurine.

EXAMPLE 11

Preparation of 6-Chloropurine

To a solution of phosphorous oxychloride (1650 g, 10.7 mole) and N,N-Dimethyl aniline (230 g, 1.9 mole), 6-hydroxypurine (100g, 0.73 mole) was added and heated to reflux for 1 hr. The reaction mixture was concentrated under vacuum at 60°C and dichloro methane (1000 ml) was added at ambient temperature, after cooling to 0°C, dry HCI gas was passed into the solution to initiate complete precipitation. The reaction mixture was kept at room temperature overnight and nitrogen gas purged into the solution to expel excess of HCI gas. The reaction contents were filtered and wet cake washed with dichloro methane (100 ml). The filter cake was treated with DM water (100 ml) and cooled to ~10°C and neutralized with liquor ammonia (25%). The precipitated solid was filtered and washed with hexane (100 ml), and dried to yield 80 g (70%) of 6-chloropurine. mp: >300°C.

EXAMPLE 12

Final preparation of 6-Furfuryl aminopurine (Kinetin):-

To a solution of 6-chloropurine (100g, 0.64 mole) in Dimethyl sulfoxide (550 ml), Furfuryl amine (166 g, 1.7 mole) was added and heated to 80-85°C (8 hrs). The mixture was cooled to ambient temperature filtered and washed with DM water (100 ml) followed by methanol (100 ml) to yield 132.6 g (95%)of 6-furfurylaminopurine. mp:269-272°C.

WE CLAIM:

1. An improved process for preparing kinetin of formula

from 6-chloro purine of formula

which comprises forming 6-hydroxy purine of formula

by a process which consists of forming

a. 2-Mercapto-4-hydroxy-6-aminopyrimidine from which again forming
b. 2-Mercapto-4-hydroxy-5-nitroso-6-aminopyrimidine from which again forming
c. 2-Mercapto-4-hydroxy-5,6-diaminopyrimidine from which again forming
d. 5,6-Diamino-4-hydroxypyrimidine from which again forming
e. 4-Hydroxy-5,6-diaminopyrimidine-2-sulfinic acid from which again forming
f. 5,6-Diamino-4-hydroxypyrimidine from which again forming
g. 6-Hydroxypurine from which again forming
h. 2-Mercapto-6-hydroxypurine from which again forming i. 6-Chloropurine from which again finally forming j. 6-Furfuryl aminopurine (Kinetin) by method /s such as herein described.

2. A process as claimed in claim 1 wherein 2-Mercapto-4-hydroxy-6-aminopyrimidine is prepared as under:

To a solution of methanol and sodium metal, cyano acetic acid ethyl ester, and thiourea were added, the reaction mixture was maintained at ambient temperature, followed by vigorous refluxing, the contents were subsequently cooled & filtered. The wet sodium salt cake obtained was dissolved in DM water under stirring and made acidic with acetic acid to pH ~ 3, the precipitated crystals were filtered and the filter cake washed with DM water, to yield 2-mercapto-4-hydroxy-6-aminopyrimidine.

3. A process as claimed in claim 2 wherein 2-Mercapto-4-hydroxy-5-nitroso-6- aminopyrimidine is prepared as under:

To a mixture of 2-mercapto-4-hydroxy-6-amino-pyrimidine in acetic acid and DM water, sodium nitrite was added portion wise the reaction mixture was further maintained, the wet cake after filtration was washed with DM water and methanol and dried to yield 2-mercapto-4-hydroxy-5-nitroso-6-aminopyrimidine.

4. A process as claimed in claim 3 wherein2-Mercapto-4-hydroxy-5,6-
diaminopyrimidine is prepared as under:

2-Mercapto-4-hydroxy-5-nitroso-6-aminopyrimidine in DM water was heated under stirring, and sodium dithionite monohydrate was added portion wise over a period, the reaction was further maintained, and subsequently cooled and filtered, the wet cake was washed with DM water, followed by methanol, on drying 2-mercapto-4-hydroxy-5,6-diaminopyrimidine was obtained.

5. A process as claimed in claim 4 wherein 2-Mercapto-4-hydroxy-5,6-
diaminopyrimidine is prepared as under:

To a mixture of 2-mercapto-4-hydroxy-5,6-diamino pyrimidine in DM water, hydrochloric acid was added and pH of the solution was adjusted, zinc dust was added to the reaction mixture over a period, while adding the hydrochloric acid to maintain the pH 5-6, after addition of Zinc dust was completed, reaction mixture was stirred, concentrated hydrochloric acid was added to lower the pH and filtered, the mother liquor was cooled and conc, sulfuric acid was added and cooled, the precipitate was filtered and washed with DM water and dried, which gave the solid which solid suspended in DM water and cooled and pH of the mixture was adjusted, filtered and dried to yield 2-mercapto-4-hydroxy-5,6-diamino pyrimidine identical in all respects with a sample obtained from reduction of 2-mercapto-4-hydroxy-5-nitroso-6-amino pyrimidine using sodium dithionite.

6. A process as claimed in claim 5 wherein 5,6-Diamino-4-hydroxypyrimidine is prepared as under:

To a solution of 2-mercapto-4-hydroxy-5,6-diamino-pyrimidine in DM water and liquor ammonia ,Raney nickel was added, the reaction mixture was heated to reflux and maintained, followed by hot filtration and water wash ,the mother liquor was concentrated to dryness under vacuum, and the residue treated with methanol, the reaction contents were acidified with IPA HCI to pH ~ 3, and further maintained, followed by filtration and methanol washing to yield 5,6-diamino-4-hydroxypyrimidine

7. A process as claimed in claim 6 wherein 4-Hydroxy-5, 6-diaminopyrimidine-2-
sulfinic acid is prepared as under:

To a pre-cooled solution of 2-mercapto-4-hydroxy-5,6-diaminopyrimidine in DM water containing sodium hydroxide, was added dropwise, mixture of hydrogen peroxide and DM water during the addition, the temperature was carefully maintained ,the reaction mixture was stirred and acidified with glacial acetic acid to pH 4 ,the precipitated solid filtered washed with DM water and methanol, and dried to yield 4-hydroxy-5,6-diaminopyrimidine-2-sulfinilic acid.

8. A process as claimed in claim 7 wherein 5,6-Diamino-4-hydroxypyrimidine is
prepared as under:

A mixture of 4-hydroxy-5,6-diamino pyrimidine-2-sulfinic acid and methanol containing dry HCIgas was stirred at ambient temperature the reaction mixture was filtered and washed with methanol, and dried to yield 5,6-diamino 4-hydroxy pyrimidine hydrochloride, identical in all respects with an sample obtained from desulfurization of 2-mercapto-4-hydroxy-5,6-diaminopyrimidine using Raney nickel.

9. A process as claimed in claim 8 wherein 6-Hydroxypurine is prepared as under:

A mixture of 5,6-diamino-4-hydroxypyrimidine and triethylorthoformate in
Dimethyl formamide was stirred and heated to reflux ,the reaction mixture was
subsequently cooled to and filtered,the wet cake was washed with methanol, and
dried to yield 6-hydroxypurine.

10. A process as claimed in claim 9 wherein 2-Mercapto-6-hydroxypurine is prepared
as under:

A mixture of 5-6-diamino-4-hydroxy pyrimidine and triethylorthoformate in dimethyl formamide was stirred, heated to reflux ,the reaction mixture was subsequently cooled and filtered,the wet cake was washed with methanol and dried to yield 2-mercapto-6-hydroxy purine.

11. A process as claimed in claim 10 wherein 6-Hydroxypurine is prepared as under:

To a solution of 2-mercapto-6-hydroxy purine in DM water and liquor Raney nickel was added the reaction mixture was heated to reflux and maintained followed by hot filtration and water wash ,the mother liquor was concentrated to dryness in vacuum and residue treated with methanol to yield 6-hydroxypurine.

12. A process as claimed in claim 11 wherein 6-Chloropurine is prepared as under:

To a solution of phosphorous oxychloride and N,N-Dimethyl aniline, 6-hydroxypurine was added and heated to reflux ,the reaction mixture was concentrated under vacuum and dichloro methane was added at ambient temperature, after cooling, dry HCI gas was passed into the solution to initiate complete precipitation, the reaction mixture was kept at room temperature overnight and nitrogen gas purged into the solution to expel excess of HCI gas. The reaction contents were filtered and wet cake washed with dichloro methane ,the filter cake was treated with DM water and cooled and neutralized with liquor ammonia, the precipitated solid was filtered and washed with hexane , and dried to yield 6-chloropurine.

13. A process as claimed in claim 12 wherein 6-Furfuryl aminopurine (Kinetin) is prepared as under:

To a solution of 6-chloropurine in Dimethyl, Furfuryl amine was added and heated, the mixture was cooled to ambient temperature filtered and washed with DM water followed by methanol to yield 6-furfurylaminopurine.