CH429760A - Process for the preparation of new pharmaceutically valuable compounds - Google Patents

Description

  

  
 



  Process for the preparation of new pharmaceutically valuable compounds
The invention relates to a process for the preparation of new pharmaceutically valuable compounds of the general formula
EMI1.1
 their salts or their quaternary compounds. In this formula, alk is a straight or branched saturated alkylene group with 1 to 4 carbon atoms, with at least 2 carbon atoms forming the chain between the group) COH and the group) NR4. Alk2 is a straight or branched, saturated lower alkylene group with at least 2 carbon atoms as a chain between the group) NR4 and the phenyl radical. R2 and R3 are identical or different and represent hydrogen, halogen, hydroxyl or alkoxy. R4 is hydrogen or a lower alkyl group.



   According to the invention, these compounds can be prepared by adding a compound of the formula
EMI2.1
 where A is a phenyl or a thienyl (2) radical, either with thienyl (2) lithium or with phenylmagnesium bromide.



   The compounds of the formula (I) prepared according to the invention can be reduced to compounds of the formula
EMI2.2
 transfer by exposing them to dehydrating conditions.



   The bases obtained in this way can be converted into the corresponding salts with the aid of inorganic or organic acids. One can also use alkali halides or other alkyl acid derivatives. win the corresponding quaternary salts.



   The new compounds and their salts have valuable central stimulating and coronary expanding properties.



   example
A solution of 12.8 g of butyllithium (0.2 mol) in 20 ml of absolute ether is cooled to 150. 8.4 g of thiophene (0.1 mol) are then added dropwise at this temperature. After half an hour, the mixture is cooled to 50 and 26.7 g (0.1 mol) of 2- {N- [3'-phenyl-3'-oxo-propyl- (1 ')]} - amino-
3-phenyl-propane added in ether. After the addition, the mixture is stirred for a further hour and then decomposed while cooling with aqueous NH4C1¯ solution. The ether layer is separated and worked up in the usual way. The resulting 2- {N- [3'-phenyl-3'-thienyl-3'-hydroxypropyl- (1 ')]} - amino-3-phenyi-propane has a boiling point of 235 to 2410 at 2 mm vacuum . The base forms a hydrochloride with a melting point of 1900.



   38.7 g (0.1 mol) of this hydroxy derivative are refluxed for 21/2 hours with a mixture of 62 ml CH8COOH, 0.4 g red phosphorus, 1.2 g iodine and 1.2 ml water. After the reaction has ended, the mixture is worked up in a known manner, the ethereal solution is concentrated and the
2- {N- [3'-phenyl-3'-thienyl-propyl- (1 ') l} -amino-
3-phenyl-prop on distilled at 0.5 mm and 280 to 3000. The base can be converted into the hydrochloride which melts at 1740.



      PATENT CLAIM
I. Process for the preparation of new pharmaceutically valuable compounds of the general formula
EMI2.3
 where allyl is a straight or branched saturated alkylene group with 1 to 4 carbon atoms, in which at least 2 carbon atoms form the chain between the group COH and the group NR4, Alk2 a straight or branched, saturated lower alkylene group with at least 2 carbon atoms as a chain between the group NR4 and the phenyl radical, R2 and R3 are identical or different and are hydrogen, halogen, hydroxyl or alkoxy, R4 is hydrogen or a lower alkyl group, characterized in that a compound of the formula
EMI2.4
 wherein A denotes a phenyl or a thienyl (2) radical,

   either with thienyl (2) lithium or with phenylmagnesium bromide.

** WARNING ** End of DESC field could overlap beginning of CLMS **.



   

 

Claims (1)

** WARNING ** Beginning of CLMS field could overlap end of DESC **. According to the invention, these compounds can be prepared by adding a compound of the formula EMI2.1 where A is a phenyl or a thienyl (2) radical, either with thienyl (2) lithium or with phenylmagnesium bromide. The compounds of the formula (I) prepared according to the invention can be reduced to compounds of the formula EMI2.2 transfer by exposing them to dehydrating conditions. The bases obtained in this way can be converted into the corresponding salts with the aid of inorganic or organic acids. One can also use alkali halides or other alkyl acid derivatives. win the corresponding quaternary salts. The new compounds and their salts have valuable central stimulating and coronary expanding properties. example A solution of 12.8 g of butyllithium (0.2 mol) in 20 ml of absolute ether is cooled to 150. 8.4 g of thiophene (0.1 mol) are then added dropwise at this temperature. After half an hour, the mixture is cooled to 50 and 26.7 g (0.1 mol) of 2- {N- [3'-phenyl-3'-oxo-propyl- (1 ')]} - amino- 3-phenyl-propane added in ether. After the addition, the mixture is stirred for a further hour and then decomposed while cooling with aqueous NH4C1¯ solution. The ether layer is separated and worked up in the usual way. The resulting 2- {N- [3'-phenyl-3'-thienyl-3'-hydroxypropyl- (1 ')]} - amino-3-phenyi-propane has a boiling point of 235 to 2410 at 2 mm vacuum . The base forms a hydrochloride with a melting point of 1900. 38.7 g (0.1 mol) of this hydroxy derivative are refluxed for 21/2 hours with a mixture of 62 ml CH8COOH, 0.4 g red phosphorus, 1.2 g iodine and 1.2 ml water. After the reaction has ended, the mixture is worked up in a known manner, the ethereal solution is concentrated and the 2- {N- [3'-phenyl-3'-thienyl-propyl- (1 ') l} -amino- 3-phenyl-prop on distilled at 0.5 mm and 280 to 3000. The base can be converted into the hydrochloride which melts at 1740. PATENT CLAIM I. Process for the preparation of new pharmaceutically valuable compounds of the general formula EMI2.3 where allyl is a straight or branched saturated alkylene group with 1 to 4 carbon atoms, in which at least 2 carbon atoms form the chain between the group COH and the group NR4, Alk2 a straight or branched, saturated lower alkylene group with at least 2 carbon atoms as a chain between the group NR4 and the phenyl radical, R2 and R3 are identical or different and are hydrogen, halogen, hydroxyl or alkoxy, R4 is hydrogen or a lower alkyl group, characterized in that a compound of the formula EMI2.4 wherein A denotes a phenyl or a thienyl (2) radical, either with thienyl (2) lithium or with phenylmagnesium bromide. II. Use of compounds of the formula (I) prepared according to patent claim I for the preparation of compounds of the formula EMI3.1 characterized by making the connections. of formula (I) exposed to dehydrating conditions.