Patent GB-1072413-A (GB)
Title: New dihydrothieno[3,2-d]pyrimidines
IPC: C07D495/04
Filed: 1964-06-17
Abstract: The invention comprises compounds of the Formula I wherein R represents a halogen atom or an aryl a free hydroxy or a C1- 5 alkylmercapto group or a group of the formula -NR3R4 (in which R3 represents a C1- 6 alkyl or an aralkyl group and R4 represents a hydrogen atom or a C1- 6 alkyl group or R3 and R4, together with the adjacent nitrogen atom, represent a heterocyclic ring which may contain a further hetero-atom and which may be substituted with a C1- 3 alkyl group or an aryl group); R1 represents a hydrogen or halogen atom, or a mercapto group, a hydroxy group (which may be free or substituted by a C1- 6 alkyl, C2- 6 alkenyl or (C1- 6 alkoxy)-C1- 6 alkyl group) or a group of the formula -NR5R6 (in which R5 represents a hydrogen atom or an amine, C1- 6 alkyl, C2- 6 alkenyl, C1- 6 hydroxyalkyl, (C1- 6 alkoxy) C1- 6 alkyl, [di-(C1- 6 alkyl) amino] C1- 6 alkyl, aryl, aralkyl or cycloalkyl group and R6 represents a hydrogen atom or a C1- 6 alkyl, C2- 6 alkenyl or C1- 6 hydroxyalkyl group or R5 and R6, together with the adjacent nitrogen atom, represent a heterocyclic ring which may contain a further hetero-atom and which may be substituted by a C1- 3 alkyl group); R2 represents (where present) a C1- 10 alkyl or phenyl group and n represents 0 or 1, and (where at least one of R, R1 and R2 represents a basic group) non-toxic acid addition salts thereof, and (where R and/or R1 represents a free hydroxy group or R1 represents a free mercapto group) non-toxic salts with bases; a process for the preparation of compounds of the Formula I (in which R1 represents a free hydroxy group) where a compound of the Formula II (in which X represents a carboxylic ester group and Y represents an oxo group) is reacted with a compound of the formula R-C(NH2)=Z or a tautomer thereof of the formula R-C(=NH)-ZH (in which Z represents an imino group); a process for the preparation of compounds of the Formula I wherein a compound of the Formula V (in which at least one of A and A1 represents a halogen atom or a free or C1- 5 alkyl substituted mercapto group and the other, if not representing a halogen atom or a free or C1- 5 alkyl substituted mercapto group, represents any of the other groups which may be represented by R and R1) is reacted with a compound of the formula R7H, whereby A1 is replaced by R7, and A either remains unreplaced or is replaced by R7 in the same reaction stage or a further reagent R8H is added to replace A by a group R8 (where R7 and R8, the same or different), represent any of the atoms or groups which may be represented by R and R1 other than a hydrogen or halogen atom or an alkyl, aryl or aralkyl group; the process for preparing compounds of the Formula I (in which R is as defined above, with the exception of a hydroxy group, and R1 represents a hydroxy group substituted by a C1- 6 alkyl, C2- 6 alkenyl or (C1- 6 alkoxy)-C1- 6 alkyl group) in which a compound of the Formula I in which R and/or R1 represents a free hydroxy group is reacted with an appropriate alkylating, alkenylating or aralkylating agent; the process for the preparation of compounds of the Formula I (in which R1 represents an amino group of the formula -NR3R4, wherein R3 and R4 are as defined above except that R3 does not represent an aryl or pyridyl group and R3 and R4 do not together represent a heterocylic group) in which the corresponding compound of the Formula I, in which R1 represents a free amino group, is reacted with an appropriate alkylating, alkenylating or aralkylating agent; and the process for the preparation of compounds of the Formula I (in which R and/or R1 represents a hydrogen atom) in which a corresponding compound of the Formula I, in which R and/or R1 represent a mercapto group, is reduced.  <FORM:1072413/C2/1> Dihydrothieno[3,2-d]pyrimidines of the Formula V may be prepared by the method described above, in which a compound of the Formula II is reacted with a compound of the formula R-C(NH2)=Z or its tautomer of the formula R-C(:NH)-ZH, or, where A and/or A1 represent free or C1- 5 alkyl substituted mercapto groups, by cyclization, e.g. by reaction of a 3 - imino - tetrahydrothiophene - 2 - carboxylic acid thioamide with a thiourea, by reacting the dihydroxy compound with P2S5, followed if desired by alkylation; or from the corresponding halogen compound by reaction with thiourea, an alkali metal hydrosulphide or an alkali metal mercaptide, or, where A and/or A1 represent halogen atoms, cyclizing a compound of the Formula II (in which X represents a carbalkoxy group) with urea and converting the resulting 2,4-dihydroxy-dihydrothieno[3,2-d]pyrimidine into the dihalo compound by known methods.  Therapeutic compositions, with cardiovascular, sedative, analgesic diuretic, cytostatic, bacteriostatic, antiphlogistic and/or antipyretic activity, which may take the forms of capsules, dragees, powders, drop solutions, suspensions, solutions, ampoules or suppositories, for oral, parenteral or rectal administration, comprise compounds of the Formula I or (where at least one of R, R1 and R2 represents a basic group) non-toxic acid addition salts thereof or (where R and/or R1 represents a free hydroxy group or R1 represents a free mercapto group) non-toxic salts thereof with bases, together with a pharmaceutical carrier.