US3200132A - Aminomethyl-benzofurans - Google Patents

Aminomethyl-benzofurans Download PDF

Info

Publication number
US3200132A
US3200132A US215530A US21553062A US3200132A US 3200132 A US3200132 A US 3200132A US 215530 A US215530 A US 215530A US 21553062 A US21553062 A US 21553062A US 3200132 A US3200132 A US 3200132A
Authority
US
United States
Prior art keywords
phenylene
group
radical
dihydro
formula
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
US215530A
Other languages
English (en)
Inventor
Werner Lincoln Harvey
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
BASF Corp
Novartis Corp
Original Assignee
Ciba Geigy Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to BE623403D priority Critical patent/BE623403A/xx
Application filed by Ciba Geigy Corp filed Critical Ciba Geigy Corp
Priority to US215530A priority patent/US3200132A/en
Priority to FR911579A priority patent/FR1344997A/fr
Application granted granted Critical
Publication of US3200132A publication Critical patent/US3200132A/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
    • C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • C07D307/81—Radicals substituted by nitrogen atoms not forming part of a nitro radical

Definitions

  • R represents a cycle-aliphatic, a carbocyclic aryl or a heterocyclic aryl radical, or salts of such compounds, as well as process for the preparation thereof.
  • a 2-(2,-3-dihydro-benzofuranyl) group R is particularly a group of the formula:
  • Substituents attached to the 1,2- phenylene radical are, for example, an aliphatic hydrocarbon radical, such as lower alkyl, e.g. methyl, ethyl,
  • n-propyl, isopr-opyl, nabu-tyl and the like, hydroxyl, etheritied hydroxyl, particularly lower alkoxy, e.g.-methoxy, ethoxy, npropyl oxy, isopropyloxy, n-butyloxy and the like, as well as lower al-kenyloxy, e.g. allyloxy, Z-methylallyloxy and the like, lower ialkylene-dioxy, e.-g. methylened-ioxy, L l-ethylenedioxy and the like, cycloalkyloxy, in.
  • cycloalkyl has from five to eight, preferably from five to six, carbon atoms, e.g. cy-clopentyloxy, cyclohexyloxy and the like, carhocyclic aryloxy, such as monocyclic carbocyclic aryloxy, e.g. phenoxy and the like,
  • carbccyclic iaryl-aliphatic et'herified hydroxyl such as monocyclic carbocyclic aryl-lower alk-oxy, for example, phenyl-lower alkoxy, e.g. .benzyloxy, l-phenylethoxy, 2- phenyleth-oxy and the like, esterilied hydroxyl, especially halogeno (representing hydroxyl esterified by a hydrohalic acid), e.g. fluoro, chloro, bromo and the like, trilluoromethyl, mercapto, etherified mercapto, such as lower alkyl-mercapto, e.g.
  • N N-d-i-lower alkyl-am1no, e.g. N,N-.d-imethylarnino, N-ethyl-tN-rnethylamino, N, N-diethylain'ino and the like, or N-acylamino,
  • N-lower alkanoyl-amino e.g. N-acetylam-ino, N- propionylamino and the like
  • N-carbocyclic aroylamino e.g. 'N-benzoylanrino and the like
  • acyl such as, for example, lower alkanoyl, e.g. acetyl, puopionyl, butyryl, isobutyryl, piualoyl and the like
  • car- bocyclic aroyl, such as monocyclic carbocyclic aroyl, e.g.
  • Substituted 1,2 pheny1ene groups are, for example, aliphatic substituted-1, 2phenylene, such as lower alkyl-1,2-
  • phenylene e.-g. methyl-1,2-phenylene (such as 3-methyl- 1,2-phenylene, 4-methy1 1;2-phenylene, 4,5-dimethyl l,2- phenylene and the like), ethyl-.l,2-phenylene (such as 4- ethy1-l;2-phenylene and the like, n-propyl-1,2-phenylene (such as 4-n-propyl-1,2-phenylene and the like), isopropyl-LZ-phenylene (such as 3-isopropyl-1,2-phenylene and the like), or any other analogous lower alkyl-l,2- phenylene radical, hydroxy-l,2phenylene (such as 3-hydroxy 1,2-phenylene, 4-hydroxy-il,2-phenylene and the like), etherified hydroxy-lQ-phenylene (such as 3-meth- 0xy-'1,Q-.phenylene, 4-methoxyl,2-phenylene, 3,4-
  • allyloxy-l,2- phenylene such as 3-iallyloxyl, 2-phenylene, 4-allyl-oxy- 1,2-phenylene and the like
  • any other analogous lower alkenyloxy-1,2-phenylene radical lower alkylenedioxy- 1,2-p'henylene e.g. rnethylenedioxy-1,2-phenylene (such as 3,4-rnethylenedioxy 1,Zaphenylene and the like), or any other analogous lower alkylenedioxy-1,2 phenylene radical, cycloa1-kyloxy-1,-2-phenylene, in which cycloalkyl has from three to eight, preferably from five to six, carbon atoms, e.g.
  • cyclopentyloxy-1,2ephenylene such as 3-cyclopentyl-oxyl-l,2-phenylene and the like
  • cyolohexyloxy-1,2- phenylene such as 4-cyclohexyloxy-1,2-phenylene and the like
  • any other analogous cycloalkyloxy-l,2-phenylene radical monocyclic carhocyclic aryloxy-1,2-phenylene, e.g.
  • phenyloxy-'1,2-phenylene (such as S-phenyloxy- 1,-2-phenylene and the like) or any other analogous monocyclic carbocyclic aryloxy l,2-phenylene radical, monocyclic carhocycl'ic aryl-lo-wer alkoxy-l,2-phenylene, such as phenyl-lower alkoxy-l,2-phenylene, e.g. benzyloxy-1,2-
  • 'phenylene such as 3-benzyloxy-l,Q-phenylene, 4-benzyloxy l, 2-phenylene and the like
  • 2-phenylethoxy-1,2- phenylene such as 3-(2-phenylethoxy)-l,2-phenylene and the like] or any other analogous mon ocyclic carbocyclic .aryl-lower alkoxy-1,2-phcnylene radical, esterified hydroxy-1,2-phenylene, particularly halogeno-xl,2-phenylene, e.g.
  • fluoro1,2-phenylene such as 3- fluoro-1,'2-p henylene, 4-fluo-ro- 1,2-phenylene and the like
  • chloro-LQ- phenylene such as 3-chlor0-l,Z-phenylene, 4-chlo-ro l,2- phenylene, 4,5dichloro-f1,Z- henylene, 3,4,5,6tetrachloro-1,2-phenylene and the like
  • ibromo-l,2-phenylene such as 4-bromo-rl,2-phenylene, 3,6-dibronro-1,2-phenylone and the like
  • mercapto-LQ-phenylene such as 4-mercapto-L'Z phen
  • methylmercapto-l,2-phenylene such as 4-rnethylmercapto-1,2-phenylene and the like
  • ethylmercapt0-1,2-phenylene such as 3-ethylrnercapto-L2- phe-nylene and the like
  • any other analogous lower alkyhnercapito-1, 2-phenylene radical, nitro-l,2-phenylene such as 3-nitro-1,2-phenylene, 4nitro-l,2-phenylene and the like
  • N,Ndimethylanrino41,2-phenylene such as 3-'N,-N- d-imethylamino-l,2-phenylene, 4-N;N-dimethy l-amirro-1,2- phenylene and the like
  • N-ethyl-N-methyl-amino-l,2- phenylene such as 4-N-ethyl-N-rnethylamino-l,2-phenylene and the like
  • N,N-diet-hylamino-l,Z-phenylene radical N-acyhamino-l, 2-phenylene, such as N-lower alkanoyl-amino-1,-2-phenylene, e.g. N-acetylamino-1,2-
  • phenylene such as 4-N-acetyl-amino-l,2-phenylene and the like
  • N-piva'loylaminod,Z-phenylene such as 4-N- pivaloylamino l,2-phenylene and the like
  • N- benzoylarnino-l,Z-phenylene such as 4- N benzoylamino- 1,2-phenylene and the like
  • any other analogous N- acyl-amino-1, 2-phenylene radical, or aCyI-LZ-phenylene such as lower alkanoyl-lfi-phenylene, e.g. ace'tyl-1,2- phenylene (such as 3-acetyll,2-phenylene, 4-acetyl-l,2-
  • p'henylene such as 3-pr-opionyl-1,Z-phenylene and the like
  • butyryI-LZ-phenyIene such as 4.butyryl-1,2-phenylene and the like
  • pivaloyl-1,2-phenylene such as 3- pivaloyl LQ-phenylene and the like
  • any other analog-ous lower alkanoyl-1,2-phenylene radical monocyclic carbocyclic anoyl-1,2-phenylene, e.g.
  • benzoyLLZ-phenylone such as 3abenzoyll,Z-phenylene, 4-benzoyll,2- phenylene and the like
  • monocyclic carbocycli-c aryl-lower alkanbyl-LZ-phenylene such as phenyl-lower alkanoyl-LZ-phenylene, 6.g.
  • phenylacetyl- 1,2-phenylen-e (such as 3-p-henylacetyl-1,2-phenylene and the like) or any other analogous monocyclic aryl-lower .alkanoyl-lgZ-phenylene radical, or any equivalent substituted 1,2-phenylene radical.
  • alkylene radical represented by C,,H in the above formula, in which the letter it may stand for a whole number from one to seven, has preferably from one to four carbon atoms (the letter 11', therefore, stands preferably for-a whole number from one to tour), which carbon atoms may be arranged in a straight or a branched carbon chain.
  • Such alkylene radicals may be represented by methylene, 1,1-cthylene, 1,2-ethylene, 1methyl-1,2-etl1- ylene, 2-methyl-1,2-ethylene, 1,3-propylene, l,4-butylene and the like, as well as 1,4-pentylene, 1,5-pentylene, 1,6-
  • a cycloaliphatic radical R is preferably saturated and represents, therefore, primarily cycloalkyl. However, it
  • a cycloalkyl group may have from five to eight, preferably from five to six, ring carbon atoms and is, therefore, primarily cyclopentyl or 'cyclohexyl, as well as cycloheptyl or cyclo- 4 isobutyl and the like, lower alkoxy, egxmethoxy, ethoxy, n-propyloxy, isopropyloxy,n-butyloxy and the like, halogeno, e.g.,fluoro, chloro, bromo and the like, or any other suitable substituent.
  • Salts of the new compounds of this invention are part1- cularly acid addition salts, such as the non-toxic, pharmaceutically acceptable acid addition salts, forexample, those with inorganic acids, e.g. hydrochloric, hydrobromic, sulfuric, phosphoric acids and the like, with organic carboxylic acids, e.g. formic, acetic, propionic, glycolic,
  • a cycloaliphatic radical having one or more than one double bond is particularly acycloalkenyl group, which has from five to eight, preferably from five to six, carbon atoms; cycloalkenyl groups are, for example, l-cyclopentenyl, 2-cyclopentenyl, 3-cyclopentenyl, l-cyclohexenyl, 2-cycl0hexenyl, 3-cyclohexenyl and the like, as well as 3.-cycloheptenyl, 2-cyclo-octenyl and the like.
  • the cycloaliphatic radicals are preferably unsubstituted, but
  • substituents such as, for example, lower alkyl, e.g. methyl, ethyl, n-propyl, isopropyl and the like, or functional groups, such as halogeno, e.g. chloro, bromo and the like, lower alkoxy, e.g. methoxy, ethoxy and the like, or any other suitable functional group.
  • a carbocyclic aryl radical R is more particularly a monocyclic carbocyclic aryl radical, e.g. phenyl or substituted phenyl, or a bicyclic carbocyclic aryl radical, e.g.
  • substituents may be attached to any of the positions available for substitution in a phenyl or naphthyl radical; such substituents are, for example, lower alkyl, e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl and the like, lower alkoxy, e.g. methoxy, ethoxy, n-propyloxy, isopropyloxy, n-butyloxy'and the like, halogeno,
  • a heterocyclic aryl radical R ' is preferably a monocyclic heterocyclic aryl radical, such as pyridyl, e.g. 2-pyridyl, 3-pyridyl or 4 pyridyl, thienyl, e.g. Z-thienyl and the like, furyl, e.g. 2-furyl and the like; these groups may contain additional substituents, such as, for example, low- .er alkyl, e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl,
  • organic sulfonic acids e.g.. methane sulfonic
  • ethane sulfonic Z-hydroxyethane sulfonic, ethane 1,2-disulfonic' acid, benzene sulfonic, p-toluene sulfonic, naphthalene 2-sulfonic' acid and the like;
  • Other acid addition salts may be useful as intermediates, for example, in the purification of the free compounds or .in the manufacture of other salts, as well as for identification and characterization purposes.
  • Salts which are primarilyused for, identification purposes are particularly those Wlih aCIdIC orin which R, is cycloalkyl having from five to eight carbon atoms and stands primarily for cyclopentyl or cyclohexyl, or phenyl, (lower alkyl)-phenyl, (lower alkoxy)-phenyl,
  • halogeno -phenyl or pyridyl
  • group R stands for hydrogen, lower alkyl, lower alkoxy, halogeno, trifluoromethyl, nitro, N,N-di-lower alkyl-a'mino or lower alkanoyl
  • letter n represents a whole number from one to four, andthe acid addition'salts of such compounds.
  • the new compounds of this invention may be used in the form of compositions for oral or: parenteral use, which contain the new compounds or the salts thereof in admixture with an organic or inorganic, solid or liquid carrier.
  • an organic or inorganic, solid or liquid carrier for making up such compositions there are employed substances. which do not react with the new compounds, such as water, gelatin, lactose, starches, stearic acid, magnesium stearate, stearyl alcohol, talc, vegetable oils, benzyl alcohols, gums, propylene glycol, polyalkylene glycols, petroleum jelly or any other known carrier used for such preparations.
  • the latter may be in solid form, for example, as tablets, dragees, capsules and the like, or in liquid form, for example, as solutions, suspensions, emulsions and the like, and, if desired, may contain auxiliary substances, such as preserving, stabilizing,
  • They may also contain, in combinatiomother useful substances.
  • the compounds of this invention may be prepared according to methods known perse. Iprefer to manufacture these compounds by treating an amine of the formula R -(C,,H2n)NI-I' in which R and the letter 12 have the previously-given meaning, with a compound of the formula R CH X, in which R has the previously-given meaning, and X represents a reactive 'esterified' hydroxyl group, and, if desired, converting a resulting salt into a free compound or into another salt, and/or, if
  • the reactive esterified hydroxyl group X in a compound of the formula R -CH -X is particularly a hydroXyl group esterified with a strong inorganic acid, such as a mineral acid, particularly a hydrohalic acid, e.g. hydrochloric, hydrobromic, hydriodic acid and the like, as well as sulfuric acid and the like, or a strong organic acid, particularly a strong organic sulfonic acid, such as a monocyclic carbocyclic aryl sulfonic acid, e.g. p-toluene sulfonic acid and the like, or a lower alkane sulfonic acid, e.g.
  • a strong inorganic acid such as a mineral acid, particularly a hydrohalic acid, e.g. hydrochloric, hydrobromic, hydriodic acid and the like, as well as sulfuric acid and the like
  • a strong organic acid particularly a strong organic sulfonic acid, such
  • the group X in the above formula is above all represented by halogeno having an atomic weight greater than 19, such as chloro, bromo or iodo.
  • the reaction is preferably carried out by treating the amine with the reactive ester compound in such a way that an excess of the amine is always present.
  • Alcohols such as lower alkanols, e.g. methanol, ethanol and the like, or any other suitable direct diluent may serve as sol- .vents.
  • an alkaline reagent such as an alkali metal carbonate, e.g. sodium or potassium carbonate or hydrogen carbonate and the like, or an organic base, e.g. pyridine and the like, may be used to neutralize the generated acid.
  • the reaction is preferably performed at an'elevated temperature, if necessary, in a closed vessel under pressure and/or in the atmosphere of an inert gas, e.g. nitrogen.
  • an inert gas e.g. nitrogen.
  • the starting materials used in the above reaction are known or may be prepared according to methods used for the preparation of the known compounds.
  • the compounds of this invention may also be prepared by reacting a compound of the formula R -CH -NH in which R has the previously-given meaning, with a compound of the formula R -(C H )X, in which R X and the letter n have the previously-given. meaning, if desired, carrying out the optional steps.
  • the compounds of this invention may also be obtained by converting in a compound of the formula in which R R and the letter n have the previouslygiven meaning, the carbonyl group into methylene, and, if desired, carrying out the optional steps.
  • Conversion of the carbonyl portion of the amide group into methylene is carried out according to known methods, particularly by treatment with a reducing reagent capable of converting the carbonyl portion of the amide grouping into methylene.
  • reducing reagents are especially alkali metal aluminum hydrides or alkaline earth metal aluminum hydrides, particularly lithium aluminum hydride as well as sodium aluminum hydride and the like; if necessary, these reagents may be used in the presence of an activator, for example, aluminum chloride and the like.
  • the reaction is carried out in the presence of a suitable solvent, for example, an ether, e.g.
  • Conversion of the carbonyl group into methylene may also be achieved by electrolytically reducing the amide on a suitable cathode, such as mercury, lead, nickel cathode and the like, using a proper anode and suitable catholyte and anolyte media. Conversion of the carbonyl portion in an amide group into methylene may also be carried out by treatment with hydrogen in the presence of asuitable catalyst, e.g. certain copper catalysts and the like.
  • a suitable cathode such as mercury, lead, nickel cathode and the like
  • the starting materials used in the above reaction may be prepared according to procedures generally used for the preparation of carboxylic acid amides, for example, by treatment of an acid halide, e.g., chloride, with an amine.
  • an acid halide e.g., chloride
  • the compounds of the present invention may also be prepared by converting in a compound of the formula R CSNH(C H )R in which R R and the letter w have the previously-given meaning, the thiocarbonyl group into methylene, and, if desired, carrying out the optional steps.
  • the above conversion of a thiocarbonyl group into a methylene group may be carried out according to known methods, for example, by treating the thioamide compound with freshly prepared Raney nickel in a suitable, particularly in an alcoholic, solvent, e.g., methanol, ethanol and the like, or electrolytically reducing it according to the procedure outlined hereinabove for the reduction of the amides.
  • a suitable particularly in an alcoholic, solvent, e.g., methanol, ethanol and the like
  • the starting materials may be prepared, for example, from the previously-described amides by treatment with liukitable reagents, e.g., phosphorus pentasulfide and the Another method for the preparation of compounds of this invention, particularly of compounds having the formula R -CH NHCH (C,, H )R in which R R and the letter n have the previously-given meaning, comprises converting in a compound having the formula (C 1Hg 2 -R2, in which R R and the letter 11 have the previously-given meaning, the thiocarbonyl group into methylene, and, if desired, carrying out the optional steps.
  • liukitable reagents e.g., phosphorus pentasulfide
  • Another method for the preparation of compounds of this invention comprises converting in a compound having the formula (C 1Hg 2 -R2, in which R R and the letter 11 have the previously-given meaning, the thiocarbonyl group into methylene, and, if
  • the reduction of the Schiff base-type double bond may be carried out by using catalytically activated hydrogen or a di-light metal hydride as hydrogenating agents.
  • Catalysts containing a metal of the eighth group of the periodic system may be used in the presence of hydrogen; for example, palladium, e.g., palladium on charcoal and the like, represents a suitable metal catalyst.
  • the reduction is carried out by treating, for example, a lower alkanol, e.g., methanol, ethanol and the like, solution of the Schiif base with hydrogen, if desired, at an increased pressure, in the presence of the catalyst.
  • the preferred reduction reagents are light metal hydrides, particularly the alkali metal borohydrides,
  • an alcohol such as a lower alkanol, e.g., methanol, ethanol, isopropanol and the like, if desired, aqueous mixtures thereof, and the like, may be used with an alkali metal borohydride; an ether, e.g., diethylether, tetrahydrofurane and the like, is used with an alkali metal aluminum hydride. If desired, the reaction may be promoted by the. addition of an activator, for example, of aluminum chloride and the like.
  • an activator for example, of aluminum chloride and the like.
  • reaction is performed at room temperature or preferably;
  • an elevated temperature for, example, at the boiling temperature of the solvent, and, if necessary, in the atmosphere of an inactive gas, e.g., nitrogen.
  • the Schifl base-type starting materials may be prepared according to methods known per se, for example, by reacting a 2-aminomethyl-2,3-dihydro-benzofuran with an aldehyde, if necessary, in the presence of a solvent, such as an alcohol, for example, a lower alkanol, e.g., methanol, ethanol and the like, and or under cooling at room temperature or at an elevated temperature.
  • a solvent such as an alcohol, for example, a lower alkanol, e.g., methanol, ethanol and the like
  • the compounds of this invention may also be prepared by removing in a compound of the formula in which R R and the letter n have the previouslygiven meaning, the Schitf base-type C N- double bond by reduction, and, if desired, carrying out the optional steps.
  • a resulting salt may be converted into the free base in the customary way,'for example,- by reaction with an alkaline reagent, such as a metal hydroxide, e.g.sodium hydroxide, potassium hydroxide and the like, a metal carbonate, e.g. sodium or potassium carbonate or hydrogen carbonate. and the like, ammonia and the like, or with a suitablehydroxyl ion exchange preparation.
  • an alkaline reagent such as a metal hydroxide, e.g.sodium hydroxide, potassium hydroxide and the like, a metal carbonate, e.g. sodium or potassium carbonate or hydrogen carbonate. and the like, ammonia and the like, or with a suitablehydroxyl ion exchange preparation.
  • a resulting salt may be converted into another salt, for example, by treating it with a metal, e.g. sodium, barium, silver and the like, salt of an acid in the presence of a suitable diluent, in which a resulting inorganic salt is insoluble, or with an anion exchange preparation.
  • a metal e.g. sodium, barium, silver and the like
  • salt of an acid in the presence of a suitable diluent, in which a resulting inorganic salt is insoluble, or with an anion exchange preparation.
  • a free base may be converted into an acid addition salt by reacting it or a solution thereof with the appropriate inorganic or organic acid, such as one of those outlined hereinbefore, or a, solution thereof, and isolating the desired salt.
  • a substituent may be introduced into the carbocyclic aryl portion of the 2,3-dihydro-benzofuran nucleus of a resulting compound.
  • a nitro group may be introduced upon nitration with a suitable nitrating reagent.
  • a resulting compound may be reacted with an organic carboxylic acid halide, e.g.chloride and the like, in the presence of 'a suitable reagent, such as aluminum chloride and the like, and an organic carboxylic acid acyl radical may be introduced.
  • substituents attached to the carbocyclic aryl portion of the 2,3-dihydro-benzofuran nucleus may be converted into other substituents.
  • a nitro group may be reduced to an amino group according to known reduction methods, for example, by controlled treatment with hydrogen in the presence of a suitable cata lyst, e.g. palladium on charcoal and the like, and of an inert solvent, e.g. p-dioxane and the like.
  • An amino group may be converted into a halogeno atom by diazotization, followed by treatment with a cuprous halide according to the Sandmeyer reaction.
  • a-lower alkoxy, e.g. methoxy and the like, group may be converted into a free hydroxyl group, for example, by acidic hydrolysis with The reductive removal of the Schiff base-type double thereon. Temperatures are given in degrees centigrade.
  • The-starting material used in the above example is prepared as follows: A mixture of 124.1 g. of guaiacol, 140 g. of powdered potassium carbonate and 121.0 g. ofallyl bromide in 150 ml. of acetone isrefluxed while stirring for eight hours. After cooling, it is poured into 1000 ml. of Water. and the organic material ,is extracted with diethyl ether. The solvent iseVapOrated, and the residue is distilled under reduced pressure to yield 129.2 g. of 2 allyloxy-anisole, B.P. /7 mm.
  • Example 2 A mixture of 4.9 g. of 2-bromomethyl-7-methoxy-2,3- dihydro-benzofuran and 4.9 g. of 2-phenylethylamine in 15 ml. of ethanol is reacted as shown in Example. 1; the resulting 7-methoxy-2- (2-phenylethyl -aminoethyl-2,3-dihydro-benzofuran of the formula:
  • Example 3 CH2 OCH CH-CHz-NH-CHrCHz- 0011 4101 precipitates and is recrystallized from ethanol, M.P. 19'6- 197.
  • the starting material is prepared according to the procedure described by R. Adams et al., J. Am. Chem. Soc., vol. 41, p. 648 (1919).
  • Example 4 To a solution of 5.1 g. of 5-acetyl-2-bromomethyl-2,3- dihydro-benzofuran in 30 ml. of ethanol is added 4.5 g. of 2-cyclopentylethyl-amine. The reaction is carried out according to the method described in Example 3; the 5 acetyl 2-(2-cyclopentylethyl) -aminoethyl-2,3-dihydrohenzofuran hydrochloride of the formula:
  • CHr-C Hg Ego-CO is recrystallized from isopropanol, M.P. 227-229.
  • the starting material which is prepared according to the method described by R. Adams et al., loc. cit. by starting with 4-hydroxy-benzophenone, has a boiling point of 170/0.05 mrn.
  • Example 5 A solution of 9.72 g. of 2-bromomethyl-7-methoxy-2,3- dihydro-benzofuran in 30 m1. of ethanol is reacted with 14.4 g. of 2-(3,4-dimethoxy-phenyl)-ethylamine according to the procedure described in Example 3; the desired 2 [2-(3,4-dirnethoxy-'pheny1)-ethyl]-aminoethyl-7-methoxy-2,3-dihydro-benzofuran hydrochloride of the formula:
  • Example 6 A solution of 5.1 g. of 5-acetyl-2-bromomethyl-2,3 dihydro-benzofuran and 4.8 g. of Z-phenylethylamine in 30 ml. of ethanol is reacted as described in Example 3 to .10 yield to 5 acetyI-Z-(Z-phenylethyl)-aminomethyl-2,3-dihydrobenzofuran hydrochloride of the formula:
  • R is phenyl
  • the group R is lower alkoxy
  • V the letter n is a whole number from one to four.
  • R is (lower alkoxy)-phenyl
  • the group R is lower alkoxy
  • the letter 11' is a whole number from one to four.
  • R stands for-cycloalkyl having from '5 to 8 ring carbon atoms, the group R is lower alkoxy, and the letter n is a whole number from one to four.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
US215530A 1962-08-08 1962-08-08 Aminomethyl-benzofurans Expired - Lifetime US3200132A (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
BE623403D BE623403A (en, 2012) 1962-08-08
US215530A US3200132A (en) 1962-08-08 1962-08-08 Aminomethyl-benzofurans
FR911579A FR1344997A (fr) 1962-08-08 1962-10-08 Procédé de préparation de benzofurannes, entre autres du 2-(2-cyclopentyléthyl)-aminométhyl-7-méthoxy-2, 3-dihydro-benzofuranne

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US215530A US3200132A (en) 1962-08-08 1962-08-08 Aminomethyl-benzofurans

Publications (1)

Publication Number Publication Date
US3200132A true US3200132A (en) 1965-08-10

Family

ID=22803338

Family Applications (1)

Application Number Title Priority Date Filing Date
US215530A Expired - Lifetime US3200132A (en) 1962-08-08 1962-08-08 Aminomethyl-benzofurans

Country Status (2)

Country Link
US (1) US3200132A (en, 2012)
BE (1) BE623403A (en, 2012)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3457281A (en) * 1965-12-08 1969-07-22 Ward Blenkinsop & Co Ltd 2-(alkoxyalkylaminomethyl)-benzofurans
US3459860A (en) * 1967-06-09 1969-08-05 Ciba Geigy Corp 2-aminomethyl-2,3-dihydrobenzofurans as antihypertensive agents
US4500543A (en) * 1982-06-01 1985-02-19 Abbott Laboratories Substituted 1-aminomethyl-phthalans
US4847254A (en) * 1987-02-26 1989-07-11 H. Lundbeck A/S CNS affecting 5-oxy-3-aminomethyl-dihydro-benzofurans and benzothiophenes

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
None *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3457281A (en) * 1965-12-08 1969-07-22 Ward Blenkinsop & Co Ltd 2-(alkoxyalkylaminomethyl)-benzofurans
US3459860A (en) * 1967-06-09 1969-08-05 Ciba Geigy Corp 2-aminomethyl-2,3-dihydrobenzofurans as antihypertensive agents
US4500543A (en) * 1982-06-01 1985-02-19 Abbott Laboratories Substituted 1-aminomethyl-phthalans
US4847254A (en) * 1987-02-26 1989-07-11 H. Lundbeck A/S CNS affecting 5-oxy-3-aminomethyl-dihydro-benzofurans and benzothiophenes

Also Published As

Publication number Publication date
BE623403A (en, 2012)

Similar Documents

Publication Publication Date Title
HU193161B (en) Process for preparing new n-alkyl-norscopines
US4172095A (en) Novel synthesis of 3-amino-2-methylbenzotrifluoride and the intermediates thereof
US3106564A (en) 1-(2-phenoxy-2-phenylethyl) pyrrolidine
CA1330560C (en) Di- and tetrahydroisoquinoline derivatives
US4978793A (en) Novel process for the preparation of serinol
US3200132A (en) Aminomethyl-benzofurans
SU489322A3 (ru) Способ получени замещенных 3-(2/4-фенил-1-пиперазинил/-этил) индолинов или их солей или их четвертичных аммониевых солей
US3631039A (en) 2-amino ethyl-2-hydroxy - 6-vinyl tetrahydropyrans tautomers and optical enantiomers thereof
US3139455A (en) Phenoxyacetamidoximes
US3551414A (en) 6,7-dihydro-5h-dibenz(c,e)azepin-7-ones
IL25315A (en) O-(2-guanidino-ethyl)-oximes
US3509162A (en) Phenethyl carbamates
Sato Azirines. IV. The photolysis of β-azidovinyl ketones
US3398155A (en) 2, 6-dichloro-isonicotinamide derivatives and a method for their preparation
HU182719B (en) Process for preparing basically substituted aralkyl-amino-alkyl-phenyl-acetonitriles
US3157674A (en) 2-(cycloaliphatic-alkyl-aminomethyl)-benzodioxanes
US3320277A (en) 3-amino-3-hydroxymethylalkynes
US2870164A (en) Process for making d, l-methysticin and d, l-dihydromethysticin
US4506078A (en) 7-Nitroindoles
US3117131A (en) Method for producing indoline-6-sulfonamides
US3832365A (en) Quinone intermediates for synthesis of 6-hydroxydopamine
US4024127A (en) Process for the preparation of 5-alkyl-10-amino-dihydrodibenzoazepines
US3113950A (en) Process for the preparation of cyclohepta [b] pyrrol-8(1h)-one derivatives
US3124598A (en) Aminoalkoxy substituted benzodioxanes
US3694463A (en) 3-vinyl-cyclo penta (fm{11 )benzopyrans