CH545296A - 4-amino-6,7,8-trimethoxyquinazolines - Google Patents

Abstract

4-Amino-6,7,8-trimethoxyquinazolines Cpds. of formula (I) (where Y, Y1 and Y2 are 1-3C alkoxy and R and R1 are H, 1-4C alkyl or a group -CH2(CH2)nONO2 (a), -CH2(CH2R2)nONO2 (b) or -CH2(CH2)zN CH2(CH2)zONO2 2 (c) in which R2 is -(CH2)mCH3 or -(CH2)yONO2, n is 1-6, m is 0-4 (7+n is not >6) y is 1-4 (n+y is not >7) and z is 1-4, at least one and not more than two nitrate groups being present and one of R and R1 being H or alkyl when the other is a group (b), or NRR1 is a residue and corr. cpds. in which -ONO2 residues are replaced by OH, have hypotensive and coronary dilating activity, some also have antiarrhythmic activity.

Description

  

  
 



   The invention relates to a process for the preparation of 6,7,84rialkoxyquinazolin-4 + 3H) ones of the formula I,
EMI1.1
 where Y, Y and Y2 can be identical or different and each represent alkoxy having 1-3 carbon atoms.



   The inventive method is characterized in that compounds of the formula II,
EMI1.2
 wherein Y, Y1 and Y2 have the above meanings, condensed with formamide.



   The process is carried out in a manner known per se, for example at the reflux temperature of the reaction mixture.



   The compounds of the formula II are known or can be prepared in a manner known per se. You can get to them, for example, by using compounds of formula III,
EMI1.3
 where Y, Y, and Y2 have the above meanings, reduced.



  The process can be carried out in a conventional manner, for example by catalytic hydrogenation, e.g. using a palladium carbon catalyst.



   The compounds of the formula III are known or can be prepared in a manner known per se.



   The compounds of the formula I represent intermediates and can be used, for example, for the production of valuable pharmaceuticals.



   Example 6,7,8-Trimethoxyquinazolin-4 (3H) -one a) 2-Amino-3,4,5-trimethoxymethylbenzoate
A mixture of 39 g of 2-nitro-3,4,5-trimethoxymethyl benzoate, 100 ml of acetic acid and 2.5 g of 5% palladium on carbon is treated with hydrogen at a temperature of 600 ° C. for 25 hours under a pressure of 3.5 kg / cm2 shaken. It is then filtered off and concentrated in vacuo. The residue obtained is partitioned between methylene chloride and an excess of sodium carbonate solution. The methylene chloride solution is dried and concentrated in vacuo, and after distillation of the oil obtained in this way (105 ° C., 5 × 10-3 mm), an oil of 2-amino-3,4,5-trimethoxymethyl benzoate is obtained.



  b) 6,7,8-TrFrnethoxShiruzolin-4 (3H) -one
A solution of 24.2 g of 2-amino-3,4,5-trimethoxymethylbenzoate in 80 ml of 99% formamide is refluxed for 1.25 hours. The reaction mixture is cooled, 200 ml of ice water are added, the solid is filtered off, washed with water and dried, giving 6,7,8-trimethoxyquinazolin-4 (3H) one with a melting point of 2202220C.

 

      PATENT CLAIM
Process for the preparation of 6,7,8-trialkoxyquin azolin-4 (3H) ones of the formula I,
EMI1.4
 in which Y, Y1 and Y2 can be identical or different and are each alkoxy with 1-3 carbon atoms, characterized in that compounds of the formula II,
EMI1.5
 wherein Y, Y1 and Y have the above meanings, condensed with formamide.

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



   

 

Claims (1)

** WARNING ** Beginning of CLMS field could overlap end of DESC **. The invention relates to a process for the preparation of 6,7,84rialkoxyquinazolin-4 + 3H) ones of the formula I, EMI1.1 where Y, Y and Y2 can be identical or different and each represent alkoxy having 1-3 carbon atoms. The inventive method is characterized in that compounds of the formula II, EMI1.2 wherein Y, Y1 and Y2 have the above meanings, condensed with formamide. The process is carried out in a manner known per se, for example at the reflux temperature of the reaction mixture. The compounds of the formula II are known or can be prepared in a manner known per se. You can get to them, for example, by using compounds of formula III, EMI1.3 where Y, Y, and Y2 have the above meanings, reduced. The process can be carried out in a conventional manner, for example by catalytic hydrogenation, e.g. using a palladium carbon catalyst. The compounds of the formula III are known or can be prepared in a manner known per se. The compounds of the formula I represent intermediates and can be used, for example, for the production of valuable pharmaceuticals. Example 6,7,8-Trimethoxyquinazolin-4 (3H) -one a) 2-Amino-3,4,5-trimethoxymethylbenzoate A mixture of 39 g of 2-nitro-3,4,5-trimethoxymethyl benzoate, 100 ml of acetic acid and 2.5 g of 5% palladium on carbon is treated with hydrogen at a temperature of 600 ° C. for 25 hours under a pressure of 3.5 kg / cm2 shaken. It is then filtered off and concentrated in vacuo. The residue obtained is partitioned between methylene chloride and an excess of sodium carbonate solution. The methylene chloride solution is dried and concentrated in vacuo, and after distillation of the oil obtained in this way (105 ° C., 5 × 10-3 mm), an oil of 2-amino-3,4,5-trimethoxymethyl benzoate is obtained. b) 6,7,8-TrFrnethoxShiruzolin-4 (3H) -one A solution of 24.2 g of 2-amino-3,4,5-trimethoxymethylbenzoate in 80 ml of 99% formamide is refluxed for 1.25 hours. The reaction mixture is cooled, 200 ml of ice water are added, the solid is filtered off, washed with water and dried, giving 6,7,8-trimethoxyquinazolin-4 (3H) one with a melting point of 2202220C. PATENT CLAIM Process for the preparation of 6,7,8-trialkoxyquin azolin-4 (3H) ones of the formula I, EMI1.4 in which Y, Y1 and Y2 can be identical or different and are each alkoxy with 1-3 carbon atoms, characterized in that compounds of the formula II, EMI1.5 wherein Y, Y1 and Y have the above meanings, condensed with formamide.