Patent GB-1311499-A (GB)
Title: Aminoalkylaminothienopyrimidines
IPC: C07D495/04
Filed: 1970-08-07
Abstract: 1311499 2 - Aminoalkylamino - 4 - aminothienopyrimidine derivatives DR KARL THOMAE GmbH 7 Aug 1970 [8 Aug 1969 2 July 1970(2)] 38150/70 Heading C2C Novel compounds of Formula I (wherein R 1  and R 2 , which may be the same or different, each represents a hydrogen atom or a straight or branched alkyl group with from 1 to 6 carbon atoms; or R 1  and R 2 , together with the nitrogen atom to which they are attached, form a saturated 5- to 7-membered monocyclic, heterocyclic ring which may optionally be interrupted by an oxygen atom or a further nitrogen atom and/or substituted by an alkyl group or a hydroxy group; R 3  represents a hydrogen atom or a straight or branched alkyl group with 1 to 6 carbon atoms; R 4  represents a hydrogen atom or a methyl group; and A represents a straight or branched alkylene chain with from 2 to 10 carbon atoms) and their acid addition salts are prepared by one of the following methods; (a) a compound of Formula II wherein Z is halogen, alkylmercapto or alkylsulphonyl is reacted with a diamine wherein X is H or a protecting group and any protecting group X in the intermediate (e.g. X is phthalimido, acetyl or tosyl) is subsequently removed; (b) a compound of Formula IV wherein Z<SP>1</SP> is as Z above, is reacted with an amine R 1 .NH.R 2  and any protecting group X is subsequently removed; (c) a compound of Formula VI wherein Z<SP>11</SP> is a halogen atom, is reacted with ammonia or with a carboxylamide or carboxylimide or salt thereof and the amide or imide formed is subsequently cleaved; (d) a compound of Formula VII where A<SP>1</SP> is A less one CH 2  is reduced by catalytic hydrogenation; or (e) where -NR 1 R 2  in the product is an optionally alkyl substituted morpholine group by intra-molecular cyclization of a compound of Formula VIII wherein one of R 5  or R 6  is H or alkyl and the other is H; in all cases with optionally salt formation. Intermediates of Formula II above are prepared by reaction of an amine R 1 NHR 2  with a compound of Formula XI which is prepared by halogenation of a compound of Formula X wherein B is OH, obtained by reaction of urea and a compound of Formula IX 2 - (2 - Aminoethyl)amino - 4 - chloro - thieno- (3,2d)pyrimidine is obtained by action of POCL 5  on the 4-hydroxy compound which is obtained by reacting 1,2-diaminoethane with 2 - ethylmercepto - 4 - hydroxy - thieno(3,2 - d)- pyrimidine prepared by the ethylation of the 2-mercapto compound which is obtained by reacting methyl 3-aminothiophene-2-carboxylate with HCl and potassium thiocyanate followed by heating with NaOH. Intermediates of Formula VI above wherein -NR 1 R 2  is morpholino are prepared by halogenation with SOCl 2  of the corresponding intermediate wherein Z<SP>11</SP> is OH obtained by reaction of 2-chloro-4-morpholino-thieno(3,2-d)- pyrimidine with the appropriate aminoalcohol. 2 - Methylsulphonyl - 4 - morpholino - thieno- (3,2d)pyrimidine is prepared by oxidation of the corresponding 2-methylthio compound obtained by reaction of morpholine with the 4-chloro compound prepared by action of POCl 5  on 2 - methylmercapto - 4 - hydroxy - thieno- (3,2d)pyrimidine. 2 - (2 - Aminoethyl)amino - 4 - mercaptothieno(3,2d)pyrimidine is prepared by action of PS 5  in the 4-hydroxy compound and is methylated to give the 4-methylthio compound. Intermediates of Formula VII above are prepared by action of R 3 HNA<SP>1</SP>CN on a compound of Formula II above. Pharmaceutical compositions in conventional forms for oral, rectal or parenteral administration and having cardiovascular and/or sedative activity, particularly inhibiting aggregation of thrombocytes, comprise an above novel compound or salt and a carrier or diluent therefor.