according to one aspect of the present , there is provided a novel process for the preparation of 4 -[[ 6 - chloro - 2 -[( 4 - cyanophenyl ) amino ]- 4 - pyrimidinyl ] oxy ]- 3 , 5 - dimethylbenzonitrile of formula i : in the presence of a base to obtain a compound of formula i . preferably the base used in the process may be organic base or inorganic base and more preferable base is inorganic base selected from alkali metal hydroxides , alkali metal carbonates or alkali metal bicarbonates . still more preferable base is potassium carbonate . the reaction may preferably be carried out in a solvent selected from n - methylpyrrolidone , dimethylformamide , dimethylacetamide and dioxane , and more preferable solvent is n - methylpyrrolidone . according to another aspect of the present invention , there is provided a process for the preparation of etravirine crystalline form i , which comprises : a ) providing a solution of etravirine in an organic solvent ; b ) adding a solvent selected from water and hydrocarbon solvent to the solution obtained in step ( a ); and c ) isolating etravirine crystalline from i . etravirine used in step ( a ) may preferably be etravirine obtained by the known process or etravirine crystalline form ii of the invention or etravirine crystalline form iii of the invention . the organic solvent used in step ( a ) may preferably be a solvent or mixture of solvents selected from the group consisting of an alcoholic solvents such as methanol , ethanol and isopropyl alcohol ; an ester solvents such as ethyl acetate , methyl acetate , isopropyl acetate , tert - butyl methyl acetate and ethyl formate ; acetonitrile ; dimethylformamide ; dimethylsulfoxide ; an chlorinated solvents such as methylene chloride , chloroform , carbontetrachloride and ethylene dichloride ; an ether solvents such as tetrahydrofuran , 1 , 4 - dioxane , tert - butyl methyl ether and diethyl ether ; n - methylpyrrolidone and dimethylacetamide . more preferable solvent is an ether solvent , n - methylpyrrolidone and dimethylacetamide , and still more preferable solvent is tetrahydrofuran , 1 , 4 - dioxane , n - methylpyrrolidone and dimethylacetamide . the hydrocarbon solvent used in step ( b ) may preferably be a solvent or mixture of solvents selected from cyclohexane , hexane , n - heptane , benzene , toluene and xylene , and more preferable hydrocarbon solvent is n - heptane . the reaction in step ( b ) may optionally be carried out in the presence of etravirine crystalline form i crystals . isolation of etravirine crystalline form i in step ( c ) may preferably be performed by conventional techniques such as centrifugation and filtration . according to another aspect of the present invention , there is provided a crystalline form of etravirine designated as form ii characterized by peaks in the powder x - ray diffraction spectrum having 2θ angle positions at about 11 . 1 , 12 . 2 , 13 . 1 , 13 . 8 , 18 . 1 , 18 . 4 , 19 . 8 , 21 . 3 , 22 . 7 , 22 . 9 , 24 . 5 and 27 . 2 ± 0 . 2 degrees . the powdered x - ray diffractogram ( pxrd ) of etravirine crystalline form ii is shown in fig2 . according to another aspect of the present invention , there is provided a process for the preparation of etravirine crystalline form ii , which comprises : a ) providing a solution of etravirine in a mixture of alcoholic solvent and chlorinated solvent in a ratio of 0 . 7 : 1 to 1 . 2 : 1 ; b ) removing the solvent completely from the solution obtained in step ( a ); and c ) drying the solid obtained in step ( b ) to obtain etravirine crystalline from ii . etravirine used in step ( a ) may preferably be etravirine obtained by the known process or etravirine crystalline form i or etravirine crystalline form iii of the invention . the alcoholic solvent used in step ( a ) may preferably be a solvent or mixture of solvents selected from methanol , ethanol and isopropyl alcohol , and more preferable alcoholic solvent is methanol . the chlorinated solvent used in step ( a ) may preferably be a solvent or mixture of solvents selected from methylene chloride , chloroform , carbontetrachloride and ethylene dichloride , and more preferable chlorinated solvent is methylene dichloride . removal of the solvent in step ( b ) may be carried out at atmospheric pressure or at reduced pressure . removal of the solvent may preferably be carried out until the solvent is almost completely distilled off . the reaction in step ( b ) may optionally be carried out in the presence of etravirine crystalline form ii crystals . drying of the solid in step ( c ) may be carried out at 45 to 55 ° c . under high vacuum . according to another aspect of the present invention , there is provided a crystalline form of etravirine designated as form iii characterized by peaks in the powder x - ray diffraction spectrum having 2θ angle positions at about 6 . 0 , 8 . 7 , 9 . 1 , 11 . 2 , 12 . 1 , 13 . 7 , 18 . 1 , 19 . 8 , 22 . 9 , 24 . 4 , 25 . 3 and 27 . 3 ± 0 . 2 degrees . the powdered x - ray diffractogram ( pxrd ) of etravirine crystalline form iii is shown in fig3 . according to another aspect of the present invention , there is provided a process for the preparation of etravirine crystalline form iii , which comprises : a ) stirring a solution of etravirine in a mixture of alcoholic solvent and chlorinated solvent in a ratio of 1 . 3 : 1 to 2 : 1 ; b ) removing the solvent partially or completely from the solution obtained in step ( a ); c ) adding ether solvent to the reaction mass obtained in step ( b ); and d ) isolating etravirine crystalline from iii . etravirine used in step ( a ) may preferably be etravirine obtained by the known process or etravirine crystalline form i or etravirine crystalline form ii of the invention . the alcoholic solvent used in step ( a ) may preferably be a solvent or mixture of solvents selected from methanol , ethanol and isopropyl alcohol , and more preferable alcoholic solvent is methanol . the chlorinated solvent used in step ( a ) may preferably be a solvent or mixture of solvents selected from methylene chloride , chloroform , carbontetrachloride and ethylene dichloride , and more preferable chlorinated solvent is methylene dichloride . removal of the solvent may be carried out in step ( b ) at atmospheric pressure or at reduced pressure . removal of the solvent may preferably be carried out until the solvent is almost completely distilled off . the ether solvent used in step ( c ) may preferably be a solvent or mixture of solvents selected from tetrahydrofuran , 1 , 4 - dioxane , tert - butyl methyl ether and diethyl ether , and more preferably ether solvent is tert - butyl methyl ether . the reaction in step ( c ) may optionally be carried out in the presence of etravirine crystalline form iii crystals . isolation of etravirine crystalline form iii in step ( d ) may preferably be performed by conventional techniques such as centrifugation and filtration . according to another aspect of the present invention , there is provided a pharmaceutical composition comprising novel crystalline forms of etravirine selected from crystalline form ii and crystalline form iii or a mixture thereof ; and a pharmaceutically acceptable excipient . the pharmaceutically acceptable inert carrier which can be used may be a solid to or liquid . the solid pharmaceutical preparation is in the form of tablets , capsules , powders and pills . the liquid pharmaceutical preparation includes solutions , suspensions , syrups , elixirs and emulsions . the invention will now be further described by the following examples , which are illustrative rather than limiting . a solution of p - aminobenzonitrile ( 100 gm ), ethanol ( 500 ml ), concentrated nitric acid ( 36 ml ) and aqueous cyanamide ( 50 %, 54 ml ) was heated at reflux . the solution was maintained for 16 hours at reflux . the reaction mass was further cooled to 0 ° c . and then added methyl tert - butyl ether ( 500 ml ) at 0 to 5 ° c . the reaction mass was maintained for 5 hours at 0 to 5 ° c . and separated solid obtained was collected by filtration to obtain 59 gm of guanidine nitrate . guanidine nitrate ( 59 gm ) was dissolved in water ( 590 ml ) and then added sodium hydroxide solution ( 1m , 325 ml ). the separated solid obtained was filtered and dried to obtain 33 gm of 1 -( 4 - cyanophenyl ) guanidine . diethyl malonate ( 30 gm ) was added to 1 -( 4 - cyanophenyl ) guanidine ( 30 gm ) at room temperature . a solution of sodium ( 17 . 2 gm ) in ethanol ( 450 ml ) was added to the above reaction mass . the contents were heated to reflux and maintained for 12 hours . distilled off the solvent completely under vacuum and then added water ( 500 ml ). the reaction mass was stirred for 30 minutes and filtered . the solid obtained was dried to obtain 40 gm of 4 -( 4 , 6 - dihydroxypyrimidine - 2 - yl - amino ) benzonitrile . phosphoryl chloride ( 159 ml ), n , n - dimethyl aniline ( 118 ml ) and 4 -( 4 , 6 - dihydroxypyrimidine - 2 - yl - amino ) benzonitrile ( 40 gm ) are added and heated to reflux . the reaction mass was maintained for 6 hours at reflux and then poured into ice water ( 1000 ml ). the reaction mass stirred for 2 hours at room temperature and filtered . the solid obtained was dried to obtain 35 gm of 4 -( 4 , 6 - dichloropyrimidine - 2 - yl - amino ) benzonitrile . 4 -( 4 , 6 - dichloropyrimidine - 2 - yl - amino ) benzonitrile ( 35 gm ) as obtained in preparative example 3 was added to 4 - hydroxy - 3 , 5 - dimethylbenzonitrile ( 22 gm ) and then added a mixture of n - methylpyrrolidone and potassium carbonate ( 22 gm ) at 45 ° c . the reaction mass was stirred for 12 hours at 45 ° c . and then added water ( 1000 ml ). the reaction mass was cooled to 25 ° c . and stirred for 2 hours at 25 ° c ., filtered . the wet solid obtained was dissolved in acetone ( 140 ml ) under stirring and the separated solid was filtered , and then dried at 50 ° c . to obtain 24 gm of 4 -[[ 6 - chloro - 2 -[( 4 - cyanophenyl ) amino ]- 4 - pyrimidinyl ] oxy ]- 3 , 5 - dimethylbenzonitrile . 4 -[[ 6 - chloro - 2 -[( 4 - cyanophenyl ) amino ]- 4 - pyrimidinyl ] oxy ]- 3 , 5 - dimethyl - benzonitrile ( 24 gm ) was dissolved in aqueous ammonia ( 240 ml ) and 1 , 4 - dioxane ( 274 ml ) at room temperature . the contents were heated to 120 ° c . and maintained for 12 hours at 120 ° c . to the reaction mass was added water ( 360 ml ) and the reaction mass was slowly cooled to 50 to 60 ° c . the reaction mass was further cooled to 0 to 5 ° c . and stirred for 1 hour at 0 to 5 ° c ., filtered . the wet solid obtained was dissolved in toluene ( 150 ml ) under stirring . the separated solid was filtered and dried at 50 ° c . to obtain 10 gm of 4 -[[ 6 - amino - 2 -[( 4 - cyanophenyl ) amino ]- 4 - pyrimidinyl ] oxy ]- 3 , 5 - dimethylbenzonitrile . 4 -[[ 6 - amino - 2 -[( 4 - cyanophenyl ) amino ]- 4 - pyrimidinyl ] oxy ]- 3 , 5 - dimethyl - benzonitrile ( 10 gm ) was dissolved in dichloromethane ( 100 ml ) at 0 to 5 ° c . and then added bromine solution ( 4 . 7 gm in 50 ml of dichloromethane ). the reaction mass was stirred for 4 hours at 0 to 5 ° c . and then added water ( 100 ml ). the ph of the reaction mass was adjusted to 9 to 10 with sodium hydroxide solution ( 4n , 10 ml ). sodium metabisulphite solution ( 0 . 5 gm in 2 ml of water ) was added to the reaction mass and ph of the reaction mass was maintained between 7 . 5 to 8 . 5 with sodium hydroxide solution ( 4n , 10 ml ). the separated solid was filtered and dried at 50 to 55 ° c . to obtain crude etravirine . crude etravirine obtained above was dissolved in acetone ( 200 ml ) at 50 to 55 ° c . and then treated with activated charcoal ( 1 . 5 gm ). the reaction mass was filtered through celite and the filtrate was distilled off acetone completely to obtain residue . the residue was cooled to 5 to 10 ° c . and filtered . the solid obtained was dried at 60 ° c . to obtain 5 . 2 gm of pure etravirine . etravirine ( 500 mg ) as obtained example 3 was dissolved in tetrahydrofuran ( 5 ml ) under stirring at room temperature . the insolubles were filtered . to the filtrate was added n - heptane ( 15 ml ) and stirred for 1 hour at room temperature . the separated solid was filtered and dried under vacuum for 1 hour to obtain 460 mg of etravirine crystalline form i . etravirine ( 2 gm ) was dissolved in 1 , 4 - dioxane ( 25 ml ) under stirring at room temperature . the insolubles were filtered . to the filtrate was added n - heptane ( 60 ml ) and stirred for 1 hour at room temperature . the separated solid was filtered and dried under vacuum for 1 hour to obtain 1 . 8 gm of etravirine crystalline form i . etravirine ( 500 mg ) was dissolved in n - methylpyrrolidone ( 5 ml ) at room temperature . to the reaction mass was added water ( 10 ml ) and stirred for 2 hour at room temperature , filtered . the solid obtained was dried under vacuum for 1 hour to obtain 450 mg of etravirine crystalline form i . etravirine ( 1 gm ) was dissolved in dimethylacetamide ( 10 ml ) at room temperature . to the reaction mass was added water ( 18 ml ) and stirred for 2 hour at room temperature , filtered . the solid obtained was dried under vacuum for 1 hour to obtain 0 . 85 gm of etravirine crystalline form i . example 4 was repeated using methyl tert - butyl ether solvent instead of tetrahydrofuran solvent to obtain etravirine crystalline form i . example 4 was repeated using methylene dichloride solvent instead of tetrahydrofuran solvent to obtain etravirine crystalline form i . example 4 was repeated using ethyl acetate solvent instead of tetrahydrofuran solvent to obtain etravirine crystalline form i . example 4 was repeated using methanol solvent instead of tetrahydrofuran solvent to obtain etravirine crystalline form i . example 4 was repeated using dimethylformamide solvent instead of tetrahydrofuran solvent to obtain etravirine crystalline form i . example 4 was repeated using dimethylsulfoxide solvent instead of tetrahydrofuran solvent to obtain etravirine crystalline form i . etravirine crystalline form ii ( 2 gm ) was dissolved in tetrahydrofuran ( 18 ml ) under stirring at room temperature . the insolubles were filtered . to the filtrate was added n - heptane ( 55 ml ) and stirred for 1 hour at room temperature . the separated solid was filtered and dried under vacuum for 1 hour to obtain 1 . 8 gm of etravirine crystalline form i . example 14 was repeated using etravirine crystalline form iii instead of etravirine crystalline form ii to obtain etravirine crystalline form i . etravirine ( 500 mg ) was dissolved in a mixture of methanol ( 30 ml ) and methylene dichloride ( 30 ml ) at room temperature . the insolubles were filtered . the filtrate was stirred for 15 minutes and distilled off the solvent completely under vacuum . the solid obtained was dried under high vacuum for 15 minutes to obtain 460 mg of etravirine crystalline form ii . etravirine ( 2 gm ) was dissolved in a mixture of methanol ( 110 ml ) and methylene dichloride ( 120 ml ) at room temperature . the insolubles were filtered . the filtrate was stirred for 15 minutes and distilled off the solvent completely under vacuum . the solid obtained was dried under high vacuum for 15 minutes to obtain 1 . 8 gm of etravirine crystalline form ii . example 16 was repeated using ethanol solvent instead of methanol solvent to obtain etravirine crystalline form ii . example 16 was repeated using etravirine crystalline form i instead of etravirine to obtain etravirine crystalline form ii . example 16 was repeated using etravirine crystalline form iii instead of etravirine to obtain etravirine crystalline form ii . etravirine ( 500 mg ) was dissolved in a mixture of methanol ( 36 ml ) and methylene dichloride ( 24 ml ) at room temperature . the reaction mass was stirred for 12 hours at room temperature and the insolubles were filtered . the filtrate was distilled off the solvent completely under vacuum to obtain a residue . to the residue was added tert - butyl methyl ether ( 20 ml ) and stirred for 15 minutes at room temperature . the separated solid was filtered and dried under vacuum for 10 minutes to obtain 455 mg of etravirine crystalline form iii . etravirine ( 1 mg ) was dissolved in a mixture of methanol ( 80 ml ) and methylene dichloride ( 48 ml ) at room temperature . the reaction mass was stirred for 12 hours at room temperature and the insolubles were filtered . the filtrate was distilled off the solvent completely under vacuum to obtain a residue . to the residue was added tert - butyl methyl ether ( 20 ml ) and stirred for 15 minutes at room temperature . the separated solid was filtered and dried under vacuum for 10 minutes to obtain 0 . 82 gm of etravirine crystalline form iii . example 21 was repeated using ethanol solvent instead of methanol solvent to obtain etravirine crystalline form iii . example 21 was repeated using etravirine crystalline form i instead of etravirine to obtain etravirine crystalline form iii . example 21 was repeated using etravirine crystalline form ii instead of etravirine to obtain etravirine crystalline form iii .
4 - amino ]- 4 - pyrimidinyl ] oxy ]- 3 , 5 - dimethyl - benzonitrile is a key intermediate for the preparation of etravirine . the present invention provides a process for preparation of 4 - amino ]- 4 - pyrimidinyl ] oxy ]- 3 , 5 - dimethylbenzonitrile . the present invention also provides a novel process for the preparation of etravirine crystalline form i . the present invention further provides novel crystalline forms of etravirine , processes for their preparation and pharmaceutical compositions comprising them .