Patent GB-1005025-A (GB)
Title: Naphthalene derivatives
Inventor: CROWTHER ALBERT FREDERICK
IPC: C07C323/25
Filed: 1961-12-22
Abstract: The invention comprises racemic compounds of the general formula <FORM:1005025/C2/1> wherein R1 stands for a hydrogen atom or a straight- or branched-chain alkyl radical of not more than six carbon atoms, R2 stands for an alkyl radical of more than four carbon atoms, a substituted alkyl radical, a cycloalkyl radical, optionally substituted, or an alkenyl radical, optionally substituted, or R1 and R2 are joined together with the adjacent nitrogen atom to form a heterocyclic radical, optionally substituted, and wherein the naphthalene nucleus may optionally bear one or more alkyl substituents, and the acid addition salts thereof, but excluding 1 - (2 - naphthyl) - 2 - benzylaminoethanol, 1 - (2 - naphthyl) - 2 - (2 - phenylethylamino)-ethanol, 1 - (2 - naphthyl) - 2 - cyclohexyl-aminoethanol, 1 - (2-naphthyl)-2-[2-(1,2,3,4-tetrahydronaphthyl)]aminoethanol, 1 - (2 - naphthyl) - 2 - piperidinoethanol, 1 - (2 - naphthyl) - 2 - morpholinoethanol and 1 - (2 - naphthyl) - 2 - [N - (1,2,3,4-tetrahydroisoquinolyl)] -ethanol, and the acid addition salts thereof, pharmaceutical preparations containing them, and their preparation by (a) reducing a compound of the formula <FORM:1005025/C2/2> (wherein X stands for a halogen atom and the naphthalene nucleus may optionally bear one or more alkyl substituents) and reacting the product with NHR1R2, (b) reacting a compound of the formula <FORM:1005025/C2/3> (wherein R stands for the group <FORM:1005025/C2/4> or -CHOH.CH2X and the naphthalene nucleus may optionally bear one or more alkyl substituents) with NHR1R2, (e) reducing a compound of the formula <FORM:1005025/C2/5> (wherein the naphthalene nucleus may optionally bear one or more alkyl substituents) or an acid addition salt thereof, provided that when R2 in the starting material stands for an alkyl radical substituted on the carbon atom adjacent to the nitrogen atom by an aryl, substituted aryl or heterocyclic radical the starting material is used in the free base form, (d)-in the case of compounds wherein R1 stands for a hydrogen atom and R2 stands for -CHR3R4, wherein R3\h stands for a hydrogen atom or an alkyl radical and R4 stands for an alkyl radical, provided that R3 and R4 together contain more than three carbon atoms, or wherein R3 stands for a hydrogen atom or an alkyl or substituted alkyl radical and R4 stands for an alkyl, substituted alkyl or aryl radical, optionally substituted, provided that R3 or R4 or both stands, or stand, for an alkyl radical or radicals, bearing at least one substituent or R4 stands for an aryl radical, optionally substituted, or wherein R3 stands for a hydrogen atom or an alkyl, substituted alkyl, alkenyl, substituted alkenyl, aryl or substituted aryl radical and R4 stands for an alkenyl or substituted alkenyl radical, or wherein R3 and R4 are joined to form together with the adjacent carbon atom a cycloalkyl radical, optionally substituted-reacting a compound (which may be generated in situ) of the formula <FORM:1005025/C2/6> (wherein A stands for the group CO or CHOH and the naphthalene nucleus may optionally bear one or more alkyl substituents) with R3.CO.R4 under reducing conditions, (e)-in the case of compounds wherein R1 stands for a hydrogen atom and R2 stands for -CHR3R4-reducing a compound of the formula <FORM:1005025/C2/7> (wherein the naphthalene nucleus may optionally bear one or more alkyl substituents) in the presence of R3.CO.R4, (f) reducing a compound of the formula <FORM:1005025/C2/8> (wherein R5 stands for an aldehydo radical or a radical of the formula -CH(OR6)OH, wherein R6 stands for a hydrogen atom or an alkyl radical of not more than six carbon atoms, and the naphthalene nucleus may optionally bear one or more alkyl substituents) in the presence of NHR1R2 or an acid addition salt thereof, (g)-in the case of compounds wherein -NR1R2 stands for a heterocyclic radical, optionally substituted-reducing a compound of the formula <FORM:1005025/C2/9> (wherein <FORM:1005025/C2/100> stands for a heterocyclic radical containing at least one carbonyl radical in the ring and the naphthalene nucleus may optionally bear one or more alkyl substituents) or an acid addition salt thereof, or (h)-in the case of compounds wherein R1 stands for a hydrogen atom and R2 stands for an alkyl radical of more than four carbon atoms or a substituted alkyl radical-reducing the corresponding compound wherein R2 stands for an alkenyl or substituted alkenyl radical, optionally followed in each case by acid addition salt formation and/or (in the case of compounds wherein R1 or R2 contains one or more elements of asymmetry) separation of a mixture of two or more racemic diastereoisomeric mixtures into individual racemic mixtures. The following intermediates are prepared from the starting materials indicated in parentheses: 2 - naphthylglyoxal hydrate (2 -naphthacyl bromide); 1 - (2 - naphthyl) - 2 - (2 - methyl - N - pyrrolid - 5 - onyl)ethanol (1 - (2 naphthyl) - 2 - aminoethanol and ethyl laevulinate); 2 - methoxy - 2 - (3 - methoxyphenyl)-ethylamine and its hydrochloride (3 - methoxy - b  - nitrostyrene, via 1-(3-methoxyphenyl)-2-nitroethyl methyl ether); 2-(1-methyl-2-phenyl-ethylaminoacetyl)naphthalene hydrobromide (2 - naphthacyl bromide and 1-methyl-2-phenyl-ethylamine); 6-methyl-2-naphthacyl bromide (6-methyl-2-acetonaphthone). The compounds of the invention are of value in the treatment of prophylaxis of coronary artery disease and may be administered in the form of pharmaceutical preparations (e.g. tablets, capsules, aqueous or oily solutions, aqueous or oily suspensions, emulsions, injectable aqueous or oily solutions or suspensions, and dispersible powders) containing them together with a diluent or carrier. Specification 909,357 is referred to.