Fremgangsmåde til fremstilling af benzofuranderivater eller salte heraf.

摘要

1,084,290. Benzofurans. HASSLE, APOTEKARE PAUL NORDSTROMS FABRIKER A.B. Dec. 2, 1964 [Dec. 2, 1963], No. 49068/64. Heading C2C. New compounds of Formula (I) wherein m and n are each 1 or 2, R is lower (i.e. up to 5C) alkyl, lower alkoxystyryl or a phenyl group optionally substituted by lower alkyl, lower alkoxy, lower alkylene dioxy, fluorine, chlorine, bromine or trifluoromethyl, R1 is (when n is 1) hydrogen, fluorine, chlorine, bromine, lower alkyl or lower alkoxy or together with R2 represents benzo, R2 is (when m is 1) hydrogen, fluorine, chlorine, bromine, benzoyl, lower alkyl or lower alkoxy, or (when R1 is hydrogen) nitro, amino, hydroxy, lower acyloxy, lower alkoxybenzoyloxy, lower dialkylamino or lower acylamino and, when n is 2, R1 is methyl and, when m is 2, R2 is chlorine, A is C 1-4 alkylene, R3 is hydrogen or lower alkyl, R4 is lower alkyl, #-phenylethyl or benzyl, or NR3R4 is pyrrolidino, piperidino, hexamethyleneimino, morpholino, lower dialkylmorpholino, piperazino, lower alkylpiperazino, benzylpiperazino or tetrahydropyridino, and their pharmaceutically acceptable acid addition salts, are prepared by condensing a compound of Formula (II) with a compound Y-A1-NQ3Q4 (wherein A1, Q, Q1 and Q2 correspond to A, R, R1 and R2 respectively save that hydroxy and amino groups Q2 are substituted by protecting groups replaceable by hydrogen by hydrolysis or hydrogenation, Q3 is lower alkyl or a said protecting group, Q4 is as R4, NQ3Q4 is as NR3R4 save for the piperazino groups which are substituted in the 4-position by lower alkyl, benzyl or a said protecting group, and X and Y are atoms or groups reactable together to form an ether linkage), and where necessary replacing a said protecting group, optionally followed by acylation of amino or hydroxy groups R2, the optional hydrogenation of nitro to amino groups R2 also being described. Starting materials which are 2-(R.CO)-3- HO-(R1) n (R2)m-benzofurans are preparable by methods (A) forming o-(R.COO)-chloracetophenones by acylation and treating these with NaH, (B) forming o-(R.COO)-acetophenones by acylation, bromination to o-(R.COO)- bromoacetophenones which are ring closed with NaOiPr, (C) treating o-(R.COO)-acetophenones with K 2 CO 3 to form o-(R.CO.CH 2 CO)- phenols which are ring closed with Br 2 /K 2 CO 3 . Additionally, 2 - (p - ethoxybenzoyl) - 3 - hydroxy - 6 - p - ethoxybenzoyloxy benzofuran is prepared from p-EtOPhCOCl and 2,4- diHO- #-chloroacetophenone. Pharmaceutical compositions comprise the new compounds with carriers, oral, rectal and parenteral preparations having analgesic, antipyretic, antiinflammatory, antitussive, anµsthetic and antispasmodic properties being described.