Патент USA US2403713код для вставки
Patented July 9, i946 7:15;.1? ' _ v ‘ — .v"UNITE-oz..s'rAfrEs PATENT;- OFFICE _ V PREPARATION of‘ 4.-BA,s'roKilIlii"sUBsT1-; . I . . ‘ ' TUTED I » '2-SULPHANILAMIDQPYRIML,» DINES .1- j; ' ._ . ' ' ' Jackson P.-English, Stamford, Conn, assignor to American Cyanamid Company, New York, N. Y., a corporation of Maine ' No Drawing. Application July 17, 1944, ' Serial No.'545,395 ~ 6 Claims. (Cl. 260—239.6) l ‘ This invention relates to the preparation of sulphanilamido pyrimidines. . More particularly it relates to the preparation of 2-sulphani1amido4-aminopyrimidines. ‘ V ' 2, . with or without a solvent at a temperature of about 50° C. to about 200° C. for from about one-half hour to about four hours depend-' . ing on the temperature used. The crude reac I have discovered that when 2-sulphanilamido- 5 tion product may be isolated and, puri?ed by ex 4-alkoxypyrimidines are heated with ammonia I traction with dilute alkali,.?ltration and precipi or amines having a, reactive hydrogen, reaction tation from the alkaline solution by neutraliza occurs resulting in the formation of 2‘-sulphanil- ' tion. The crude product may also be puri?ed by amido-4-(amino or substituted amino) pyrimisuspendingit in water, ?ltering and recrystalliz dines having the following structural formula: X 7 “ N/ \ \ . N / 10 ing from aqueous solution. . . > Y ‘ ' ' . - My invention will now be illustrated in greater detail by means of the following speci?c examples, . V _ which are given. for purposes of illustration and are not to be considered‘as limiting my invention , I “Germ H NI > ; 15 to ‘the particular details described therein. 2 V substituted in which X alky1 and Y radicals are hydrogen such asalkoxyalkyl, or alkyl and I' ' ’ Example 1 49 ' Parts ' of z'sulphan?amldo'4'methoxypynm' . _ cyanoalkyl, aralkyl, dialkylaminoalkyl, etc.’ idine were mixed with 400 parts of methanol It can readily be seen in the above formula that 20 and 200 parts of anhydrous ammonia and heated when the 2-sulphanilamido-e-alkoxypyrimidine for one hour at110° C. in an autoclave. After is reacted with ammonia, then X and’ Y are hycooling and the release of pressure, the alcohol drogen; when a primary amine such as methylWaS' evaporated The 2-S111Phani1amid0-4-ami amine is used, then X15 met-11571 and Y is hydro- _ ' nopyrimidine was obtained by extraction of the gen; and when a secondary amine, is used such '25 residue with dilute alkali and precipitation from as dimethylamine, both X and Y are methyl. _ ‘ the alkaline solution by neutralization. These compounds are useful as chemotherapeu- - tic agents and, also, as intermediates in the preparation of other compounds. The present invention 'is not particularly con- A yield of 23 parts was obtained melting with decomposi tion at 259° to 270° C\, T ' 30 Example 2 ' . . cerned with the method by which the 2-sulphanilamido-é-alkoxypyrimidine is produced and it may 80 parts of 2-sulphanilamido-4-methoxypyrim idine and 33 Parts Of vrdiethylaminopropyla be produced by any suitable process. These com- mine were heated together at 110° C‘. for 45 min pounds have been prepared by reacting p-nitroutes; 'I'h'e semi-liquid reaction mixture gave off 7 benzene sulphonyl chloride with 2-amino-4-al- 35 ‘gas and set to a solid. The reaction product was koxypyrimidines followed by reduction to produce suspended in water and ?ltered. The solid 2 2-su1phanilamido-4-alkoxypyrimidines. su1phani1amidO—4-(gamma — diethylaminopropyl Illustrative examples of the amines which‘ may amino) pyrimidine was crystallized from water be used in carrying out the invention are as foland had a melting point of 230° to 232° C. lows: methylamine, ethylamine, propylamine, 40 I claim: butylamine, isopropylamine, amylamine, hexyl1- A method of preparing 2—Sulphani1amid0-4 amine, phenethylamine, cyanoethylamine, phenoxyethylamine, ethoxyeth'ylamine, diethylaminoisoamylamine, diethylaminopropylamine, di- aminopyrimidines which comprises heating 170 gether a 2,- sulphanilamido—4-alkoxypyrimidine, having the formula methylaminopropylamine, dipropylaminopropyl- 45 amine, dipropylaminobutylamine, etc. ’ When my invention is carried out using am- N NHEOSOKNEF< monia or a volatile amine, it is preferable to use > a solvent such as methanol, ethanol, propanol, ' OR > N V butanol, etc., and to conduct the reaction in. a 50 in Which R is an alkyl radical, and a member of closed vesse1 such as an autoclave, the class consisting of ammonia, primary amines In carrying outithe invention, the amine is heated with a 2-sulphanilamido-4-alkoxypyrimie and Secondary amines- , V . . 2- A method of preparing 2-S111Phani18/mid0-4— dine such as 2-sulphanilamidor4-methoxypyrimiaminopyrimidines which comprises heating to-~ dine, 2-.-sulphanilamido-4-ethoxypyrimidine, etc.', 55 gether at a temperature between 50° and 200° C., 2,403,713 3 4 2-su1phanilamido - 4 - methoxypyrimidine and a member of the class consisting of ammonia, pri mary amines and secondary amines. 3. A method of preparing 2-su1phani1amido 5. A method of preparing 2-su1phani1amido-4 aminopyrimidine which comprises heating to gether 2-su1phani1amido - 4 - methoxypyrimidine and ammonia. 6. A method of preparing 2-sulphani1amido-4 pyrimidines bearing in the 4-position a- secondary amino group comprising heating together 2 su1phani1amido-4emethoxypyrimidine and a pri comprises heating together 2-su1phani1amido-4 mary amine. methoxypyrimicline and V-diethylaminopropyla 4. A method of preparing 2-sulphani1amido pyrimidines bearing in the 4-position a, tertiary 10 amino group comprising heating together 2 su1ph-ani1amido-4~methoxypyrimidine and a sec ondary amine. - . (y-diethy1aminopropy1amino) pyrimidine which mine. i \ JACKSON P. ENGLISH.