IE41032B1 - Active derivative of methylamine, therapeutic compositions containing the same and processes for preparing the said derivatives and compositions - Google Patents

Abstract

1467739 1,1-Dialkyl-alkylamines and precursors LABAZ 15 May 1975 [20 May 1974] 20738/75 Heading C2C [Also in Division A5] Compounds of formula 'wherein R 1 and B 3 are H or alkyl, alkenyl or alkynyl of up to 6 C atoms and R 2 is C 2 -C 7 alkyl, alkenyl or alkynyl, other than CH= CHR 4 or C#CR 4 (wherein R 4 is H or C 1 -C 5 alkyl), and the total number of carbon atoms in R 1 , R 2 and R 3 is not more than 13, are prepared by treating an isocyanate or formamide of the general formula wherein A is -N=C=O or -NHCHO, with a strong acid and treating the resulting acid addition salt with a base. The resulting free base may be reacted with an acid to form a pharmaceutically acceptable salt. Compounds of Formula I wherein R 1 and R 3 are C 1 -C 3 alkyl or C 2 -C 3 alkenyl or alkynyl and R 2 is -CH 2 -R 5 , wherein R 1 , R 3 and R 5 are identical, can also be prepared by heating, in an anhydrous ether, a nitrate of formula with an organo-magnesium compound of formula wherein X is Cl, Br or I, and hydrolysing the complex thus formed. Compounds of Formula I wherein R and R 3 , are H or C 1 -C 6 alkyl and R 2 is ethynyl may be prepared by reacting sodamide with a compound of Formula wherein Hal is Cl or Br. Compounds of Formula I wherein R 1 and R 3 or C 1 -C 6 alkyl and R 2 is a radical of formula -C#CR 4 (wherein R 4 is C 1 -C 5 alkyl) are prepared by reacting a compound of formula wherein Me is alkali metal, with a halide of formula wherein Hal is Cl or Br. Compounds of Formula I wherein R 1 and R 3 are H or C 1 -C 6 alkyl and R 2 is alkenyl of formula -CH=CHR 4 (wherein R 4 is H or C 1 -C 5 alkyl) are prepared by hydrogenating in an appropriate solvent, and in the presence of a Lindlar catalyst, a compound of formula Isocyanates (II) are prepared (a) by reacting an amide of formula with chlorine or bromine in an alkaline medium, or (b) by reacting an acid of formula with a chlorinating agent such as thionyl chloride or oxalyl chloride, to obtain the corresponding acyl chloride, which is then treated with a metal azide, or by heating a compound of Formula (X) with hydrogen azide in an acid medium; the isocyanate thus formed being hydrolysed immediately to the corresponding amine. Formamides (II) are prepared by heating an alcohol of formula with an alkali metal cyanide in the presence of an acid. Amides (IX) may be prepared by reacting anhydrous ammonia with acids of Formula X or with the halides thereof. Acids (X) may be prepared by reacting alcohols (XI) with formic acid in a sulphuric acid medium. Alcohols (XI) may be prepared by reacting an organo-lithium compound with an appropriate ketone in an anhydrous ether medium. Halides (V) may be prepared by treating a 1,1 - dialkyl - 1 - ethynylcarbanol with cuprous chloride and HCl in the presence of copperbronze powder and calcium chloride. The pharmaceutically acceptable acid addition salts of the compounds of Formula I are prepared by reacting the free base with an appropriate acid. [GB1467739A]