Patent GB-1013224-A (GB)
Title: Heterocyclic aminoethanols
Inventor: HEPWORTH WALTER
IPC: C07D209/08
Filed: 1962-06-21
Abstract: The invention comprises compounds of the formula <FORM:1013224/C2/1> and salts thereof wherein R1 is hydrogen or an alkyl radical, R2 is hydrogen or an alkyl, or cycloalkyl radical optionally bearing hydroxy substituents or an aralkyl radical and A is a heterocyclic ring containing one or more nitrogen, oxygen or sulphur atoms as hetero-atoms optionally substituted by one or more alkyl, alkenyl, hydroxy, or oxo radicals or by the -CH = CH-CH = CH- radical (thus forming a further benzene nucleus) but excluding 2 - amino-, 2 - methylamino-, 2 - dimethylamino-, 2-ethylamino-, 2-diethylamino-, 2-n-propylamino-, 2 - di - n - propylamino-, 2-n-butylamino-, 2 - di - n - butylamino-, 2-n-pentylamino-, 2 - di - n - pentylamino-, 2-isopropylamino- and 2-isobutylamino-, 1-(1,3-benzodioxol - 5 - yl) ethanol, 1 - (1,4 - benzodioxan - 6 - yl) - 2 - methylaminoethanol, 2-amino - 1 - quinol - 6 - yl - ethanol, 2 - diethyl-amino- and 2 - di - n - butylamino - 1 - quinol-8-yl - ethanol, 2 - methylamino - 1 - (2 - methyl-benzimidazol - 5 - yl) - ethanol and 1 - (2 - benzimidazolon - 5 - yl) - 2 - methylaminoethanol. Preferably rings A and B together form a quinoline, 1-alkyl- or 1-alkenyl-4-quinolone, chroman, 3,4 - dihydro - 1,5 - benzodioxepine, 1,4 - benzodioxan, 1,3 - benzodioxole, benzofuran, dihydrobenzofuran, thianaphthen, 2,3-dimethylindole, benzothiazole, benzoxazole, 2-benzimidazolone, dibenzofuran or phenothiazine nucleus.  The compounds are prepared by (a) reducing a haloacetyl derivative of a heterocyclic compound (AB) and reacting the product with an amine NHR1R2; (b) reacting a heterocyclic compound (AB) bearing a substituent group <FORM:1013224/C2/2> or -CHOH.CH2.  Halogen with an amine NHR1R2; (c) reducing the group R1R2N. CH2.CO- in the corresponding ketone to an aminoethanol group; (d) reacting a heterocyclic compound (AB) bearing a substituent group -CO.CH2.NH2 or -CHOH.CH2.NH2 with a carbonyl compound R3.CO.R4 (wherein R3 = H1\t alkyl or hydroxyalkyl and R4 = alkyl, hydroxyalkyl or aralkyl) under reducing conditions to give the corresponding substituted aminoethanol derivatives and (e) reducing a heterocyclic compound (AB) bearing a substituent group -COR5, wherein R5 is a radical -CHO or -CH(OR6)OR7, where R6 and R7 are represent hydrogen or C1-6 alkyl, in the presence of an amine NHR1R2.  The amino derivative used in process (d) is suitably generated in situ, e.g. by reducing corresponding compounds bearing a diazo, azido, O-benzyl, nitro, benzylamino, benzyloxycarbonylamino, hydroxyimino or cyano group.  Glyoxals and glyoxal hydrates of the heterocyclic compounds (AB) are made by oxidizing the corresponding acetyl derivatives with selenium dioxide.  6 - Acetyl - 1 - methyl - quinolone is made by condensing sodium diethyl oxaloacetate with p-aminoacetophenone to give ethyl p-acetylphenyliminosuccinate, heating in diphenyl/diphenylether mixture to give 6-acetyl-2-ethoxycarboxyl - 4 - hydroxyquinoline; hydrolysing the free acid and heating to remove the carboxylic group giving 6-acetyl-4-hydroxyquinoline, and methylating to form the desired product.  5 - Acetyl - 2,3 - dihydrobenzofuran, 6 - acetylchroman, 5 - acetyl - 2 - benzothiazolone and 7 - acetyl - 3,4 - dihydro - 1,5 - benzodioxepine are made by the action of acetyl chloride and aluminum chloride on the appropriate heterocyclic compound.  6 - Bromoacetyl - 1,4 - benzodioxan, 5-bromoacetyl 1,3 - dimethyl - 2 - benzimidazolone, 5-bromoacetyl - 2 - benzothiazolone and 7 - bromoacetyl - 3,4 - dihydro - 1,5 - benzodioxepine are made by brominating the corresponding acetylheterocyclic compounds.  6 - Isopropylaminoacetyl - 1,4 - benzodioxan, 5 - (N - isopropyl - N - methylaminoacetyl)-1,3-benzodioxole and 3,4 - dihydro - 7 - isopropylaminoacetyl - 1,5 - benzodioxepine (hydrochlorides) are made by reaction of the appropriate amine with bromoacetyl derivative of the corresponding heterocyclic compound.  5 - Aminoacetyl - 1,3 - dimethyl - 2 - benzimidazolone, 5 - aminoacetyl - 2 - benzothiazolone 5-aminoacetyl - 2 - benzimidazolone and 6 - aminoacetyl 1,4 - benzodioxan (hydrohalides) are made by treating the corresponding bromoacetyl compounds with hexamine and decomposing the resulting hexaminium salt.