US3157663A - 3-(amino-phenyl)-2-(pyridyl)-acrylonitriles - Google Patents

3-(amino-phenyl)-2-(pyridyl)-acrylonitriles Download PDF

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US3157663A
US3157663A US239089A US23908962A US3157663A US 3157663 A US3157663 A US 3157663A US 239089 A US239089 A US 239089A US 23908962 A US23908962 A US 23908962A US 3157663 A US3157663 A US 3157663A
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pyridyl
amino
phenyl
acid
salt
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Bencze William Laszlo
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BASF Corp
Novartis Corp
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/57—Nitriles

Definitions

  • the pyridyl radical Py represents 3-pyridyl or 4-pyridyl, as well as 2-pyridyl, or substituted pyridyl, such as (lower alkyl)-pyridyl, in which lower alkyl has from one to seven, preferably from one to four, carbon atoms, e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl and the like, (lower alkoxy)-pyridyl, in which lower alkoxy has from one to seven, preferably from one to four carbon atoms, e.g.
  • halogeno has preferably an atomic weight between 19 and 80, e.g. fluoro, chloro or bromo.
  • the amino group Am may stand for unsubstituted amino, N-lower alkyl-amino, e.g. N-methyl-amino, N- ethyl-amino, N-propyl-amino and the like, or N,N-dilower alkylamino, e.g. N,N-dimethyl-amino, N-ethyl-N- methyl-amino, N,N-diethyl-amino and the like.
  • the amino group Am may substitute any of the positions of the phenyl nucleus, but is attached preferably to the 4- position (p-position).
  • Salts of the compounds of this invention are acid addition salts, such as pharmaceutically acceptable, non-toxic acid addition salts with inorganic acids, e.g. hydrochloric, hydrobromic, nitric, sulfuric, phosphoric acids and the like, or with organic acids, such as organic carboxylic acids, e.g. acetic, propionic, glycolic, malonic, succinic, maleic, hydroxymaleic, fumaric, malic, tartaric, citric, benzoic, salicyclic, 4-aminosalicylic, 2-phenoxybenzoic, 2- acetoxybenzoic acid and the like, or with organic sulfonic acids, e.g.
  • inorganic acids e.g. hydrochloric, hydrobromic, nitric, sulfuric, phosphoric acids and the like
  • organic acids such as organic carboxylic acids, e.g. acetic, propionic, glycolic, malonic, succinic, maleic, hydroxymaleic, fumaric,
  • salts for identification purposes are, for example, those with acidic organic nitro compounds, e.g. picric, fiavianic, picrolonic acid and the like, or with complex metal acids, e.g. phosphotungstic, phosphomolybdic, chloroplatinic, Reinecke acid and the like.
  • the compounds of the present invention may be in the form of mixture of isomers (i.e. racem-ates and the like) or of single isomers.
  • the compounds of this invention inhibit certain functions of the adrenal cortex. Thus, they cause a decrease of the secretion of hydrocortisone (Compound F) and an increase of the excretion of corticosterone (Compound B), while the secretion of 11-desoxy-l7a-hydroxycorticosterone (Compound S) remains unchanged; it appears that they inhibit the 17a-hydroxylase enzyme system.
  • the compounds of the present invention possessing the above 3,157,663 Patented Nov. 17, 1964 2 described specific adrenal cortical inhibitory activity, can be used as diagonostic tools for the determination of the functioning of the pituitary gland, or as agents in the treatmerit of conditions due to adrenal cortical hyperf'unction, e.g.
  • the compounds of this invention may be used in the form of composition suitable for enteral or parenteral administration, which contain the pharmacologically active compounds in admixture with a pharmaceutical organic or inorganic, solid or liquid carrier.
  • a pharmaceutical organic or inorganic, solid or liquid carrier for making up the preparations there can be employed substances which do not react with the new compounds, such as water, gelatine, lactose, starches, stearic acid, magnesium stearate, talc, vegetable oils, benzyl alcohols, stearyl alcohol, tragacanth, gums, propylene glycol, polyalkylene glycols or any other known carrier used for pharmaceutical preparations.
  • the latter may be in solid form, for example, as capsules, tablets, dragees and the like, or in liquid form, for example, as solutions, suspensions, emulsions and the like. If desired, they may contain auxiliary substances, such as preserving, stabilizing, wetting, emulsifying, coloring, flavoring agents and the like, salts for varying the osmotic pressure, buffers, etc. They may also contain, in combination, other useful substances.
  • the 3-(amino-phenyl)-2-(pyridyl)-acrylonitrile compounds of this invention having the formula in which Py and Am have the previously-given meaning, or the salts thereof, may be prepared, for example, by treating a pyridyl-acetonitrile of the formula in which Py has the previously-given meaning, with an amino-benzaldehyde, of the formula Am-C H CHO, in which Am has the previously-given meaning, and, if desired, converting a resulting salt into the free compound or into another salt, and/or, if desired, converting a resulting compound into a salt thereof, and/or, if desired, separating a mixture of isomers into the single isomers.
  • the above reaction is carried out according to known methods; preferably, it is performed in the presence of a base, such as, for example, an alkali metal lower alkanolate, e.g. lithium, sodium or potassium methanolate, ethanolate, n-butanolate, tertiary butanolate and the like, a strong quaternary ammonium hydroxide, e.g. benzyl trimethyl ammonium hydroxide and the like, or any other equivalent basic reagent, e.g. piperidine and the like, and of a suitable inert solvent, e.g. methanol, ethanol and the like, if necessary, while cooling or at an elevated temperature, in a closed vessel, and/or in the atmosphere of an inert gas, e.g. nitrogen and the like.
  • a base such as, for example, an alkali metal lower alkanolate, e.g. lithium, sodium or potassium methanolate, ethanolate, n-butanolate,
  • Compounds of this invention may also be prepared by converting in a compound having the formula in which Py has the previously given meaning, or a salt thereof, the nitro group into the desired amino group Am by reduction, and, if desired, carrying out the optional steps.
  • a reducing reagent such as a metal (iron, tin and the like) in the presence of an acid (hydrochloric, sulfuric acid and the like), catalytically activated hydrogen (hydrogen in the presence of Raney nickel, platinum oxide and the like, under controlled conditions), or any other suitable reducing reagent.
  • a nitro' group may be converted into an N-lower alkylamino or an N,N-di-lower alkyl-amino group by reductive alkylation, for example by carrying out the reduction, particularly with catalytically activated hydrogen, in the presence of an aldehyde (e.g. formaldehyde and the like) or a ketone.
  • Methods for the reduction of a nitro group into an amino group Am are referred to by Wagner and Zook, Synthetic Organic Chemistry, p. 653 (Wiley, 1953).
  • the starting material used in the above precedure is prepared according to known methods, such as, for example, one of the previously mentioned procedures.
  • a salt resulting from one of the above procedures may be converted into the free base according to known methods, for example, by treatment with an alkaline reagent, such as an alkali metal hydroxide, e.g. lithium hydroxide, sodium hydroxide, potassium hydroxide and the like, an alkali metal carbonate, e.g. sodium or potassium carbonate or hydrogen carbonate and the like, ammonia, or any other suitable reagent, such as a hydroxyl ion exchange preparation and the like.
  • an alkaline reagent such as an alkali metal hydroxide, e.g. lithium hydroxide, sodium hydroxide, potassium hydroxide and the like, an alkali metal carbonate, e.g. sodium or potassium carbonate or hydrogen carbonate and the like, ammonia, or any other suitable reagent, such as a hydroxyl ion exchange preparation and the like.
  • a resulting salt may be converted into another salt, for example, by reacting the former with an inorganic salt of an inorganic or organic acid, such as a silver, sodium and the like, salt of such acid, or with a suitable anion exchange preparation.
  • an inorganic salt of an inorganic or organic acid such as a silver, sodium and the like, salt of such acid, or with a suitable anion exchange preparation.
  • a free base may be converted into a salt according to known methods, for example, by treating a solution of the base in an inert solvent or solvent mixture with the appropriate acid, such as one of the above-mentioned inorganic or organic acids, if desired, a solution thereof in an inert solvent or solvent mixture, and isolating the desired salt. Salts may be isolated in the form of hydrates.
  • racemates may be resolved into the optically active dand l-forms, for example, by treating a racemic mixture, preferably in solution with an inert solvent or solvent mixture, with one of the optically active forms of an acid containing an asymmetric carbon atom, or a solution thereof, and isolating the resulting salt.
  • optically active forms of salt-forming acids having an asymmetric carbon atom are D-tartaric (l-tartaric) acid of L-tartaric (d-tartaric) acid; the optically active forms of rhalic, mandelic, camphor-lO-sulfonic, quinic acid and the like, may also be used.
  • a resulting salt may be converted into the free and optically active base according to process as outlined hereinbefore, and an optically active base may be converted into an acid addition salt or a quaternary ammonium compound, according to the previously-mentioned methods.
  • Mixtures of other isomers, e.g. diastereoisomers are separated on the basis of physicochemical differences, e.g. solubility and the like.
  • the invention also comprises any modification of the process wherein a compound obtainable as an intermediate at any stage of the process is used as starting material and the remaining step(s) of the process is(are) carried out, as well as any new intermediates.
  • Example 1 To a solution of 6.0 g. of 4-N,N-dimethylaminobenzaldehyde and 6.0 g. of (3-pyridyl)-acetonitrile in 20 ml. of methanol is added approximately 0.1 g. of sodium methanolate while stirring. Within five minutes, the reaction mixture solidifies and is diluted with Water. The solid material is filtered off and washed with water to yield the desired 3-(4-N,N-dimethylaminophenyl)-2-(3-pyridyl) -acrylonitrile of the formula which is recrystallized from aqueous ethanol and a mixture of ethyl acetate and pentane, M.P. 142-143.
  • Example 2 To a solution of 3.0 g. of (4-pyridyl)-acetonitrile in 15 ml. of percent ethanol is added a solution of 3.7 g. of 4-N,N-diyethylamino-benzaldehyde in 10 ml. of 95 percent ethanol while stirring. Small portions of solid sodium methanolate are added until a precipitate is formed, and the mixture solidifies. Water is added, the yellow solid is filtered off and is recrystallized from a mixture of ethanol and water to yield 2.8 g. of 3-(4-N,N-dimethylamino)-2-(4-pyridyl)-acrylonitrile of the formula which melts at l81l82.
  • Example 3 To a solution of 2.5 g. of 3-(4-nitro-phenyl)-2-(4-pyridyl)-acrylonitrile in ml. of p-dioxane is added 1.0 g. of a palladium catalyst (5 percent palladium on charcoal), and the mixture is treated with hydrogen at atmospheric pressure. After the uptake of the theoretical amount of hydrogen, the hydrogenation is interrupted, the catalyst is filtered off and the filtrate is evaporated to dryness. The yellow solid is recrystallized from ethanol to yield the desired 3-(4-amino-phenyl)-2-(4-pyridyl)- acrylonitrile of the formula which melts at 224-227".
  • a palladium catalyst 5 percent palladium on charcoal
  • the starting material used in the above reaction is prepared as follows: To a solution of 3.0 g. of (4-pyridyl)-acetonitrile and 3.8 g. of 4-nitro-benzaldehyde in 95 ethanol are added while stirring small portions of solid sodium methanolate until the solution begins to darken. During the exothermic reaction a solid material precipitates, the reaction mixture is diluted with Water, and the solid material is filtered olf. The desired 3-(4-nitrophenyl) -2-(4-pyridyl) acrylonitrile melts at 199-200 after recrystallization from ethanol.

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Description

United States Patent 3,157,663 3-(AMlN0-PHENYL)-2-(PYRIDYL)- ACRYLONITRILES William Laszlo Bencze, New Providence, N.J., assignor to Ciba Corporation, New York, N.Y., a corporation of in which Py is pyridyl, and Am stands for an amino group, or salts thereof, as well as process for the preparation of these compounds.
The pyridyl radical Py represents 3-pyridyl or 4-pyridyl, as well as 2-pyridyl, or substituted pyridyl, such as (lower alkyl)-pyridyl, in which lower alkyl has from one to seven, preferably from one to four, carbon atoms, e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl and the like, (lower alkoxy)-pyridyl, in which lower alkoxy has from one to seven, preferably from one to four carbon atoms, e.g. methoxy, ethoxy, isopropyloxy, n-butyloxy and the like, (halogeno)-pyridyl, in which halogeno has preferably an atomic weight between 19 and 80, e.g. fluoro, chloro or bromo.
The amino group Am may stand for unsubstituted amino, N-lower alkyl-amino, e.g. N-methyl-amino, N- ethyl-amino, N-propyl-amino and the like, or N,N-dilower alkylamino, e.g. N,N-dimethyl-amino, N-ethyl-N- methyl-amino, N,N-diethyl-amino and the like. The amino group Am may substitute any of the positions of the phenyl nucleus, but is attached preferably to the 4- position (p-position).
Salts of the compounds of this invention are acid addition salts, such as pharmaceutically acceptable, non-toxic acid addition salts with inorganic acids, e.g. hydrochloric, hydrobromic, nitric, sulfuric, phosphoric acids and the like, or with organic acids, such as organic carboxylic acids, e.g. acetic, propionic, glycolic, malonic, succinic, maleic, hydroxymaleic, fumaric, malic, tartaric, citric, benzoic, salicyclic, 4-aminosalicylic, 2-phenoxybenzoic, 2- acetoxybenzoic acid and the like, or with organic sulfonic acids, e.g. methane sulfonic, ethane sulfonic, Z-hydroxyethane sulfonic, ethane 1,2-disulfonic, toluene sulfonic acid and the like. Other acid addition salts may be used as intermediates, for example, in the purification of the free compounds or preparation of other acid addition salts, as well as for identification or characterization purposes. Salts for identification purposes are, for example, those with acidic organic nitro compounds, e.g. picric, fiavianic, picrolonic acid and the like, or with complex metal acids, e.g. phosphotungstic, phosphomolybdic, chloroplatinic, Reinecke acid and the like.
The compounds of the present invention may be in the form of mixture of isomers (i.e. racem-ates and the like) or of single isomers.
The compounds of this invention inhibit certain functions of the adrenal cortex. Thus, they cause a decrease of the secretion of hydrocortisone (Compound F) and an increase of the excretion of corticosterone (Compound B), while the secretion of 11-desoxy-l7a-hydroxycorticosterone (Compound S) remains unchanged; it appears that they inhibit the 17a-hydroxylase enzyme system. The compounds of the present invention, possessing the above 3,157,663 Patented Nov. 17, 1964 2 described specific adrenal cortical inhibitory activity, can be used as diagonostic tools for the determination of the functioning of the pituitary gland, or as agents in the treatmerit of conditions due to adrenal cortical hyperf'unction, e.g. Cushings syndrome, primary aldosteronism, secondary aldosteronism and the like. Futhermore, the preferential inhibition of the 17u-hydroxylase enzyme system makes the compounds of this invention useful as aids in the study of the biosynthetic pathways of c'orticoid hormone formation.
The compounds of this invention may be used in the form of composition suitable for enteral or parenteral administration, which contain the pharmacologically active compounds in admixture with a pharmaceutical organic or inorganic, solid or liquid carrier. For making up the preparations there can be employed substances which do not react with the new compounds, such as water, gelatine, lactose, starches, stearic acid, magnesium stearate, talc, vegetable oils, benzyl alcohols, stearyl alcohol, tragacanth, gums, propylene glycol, polyalkylene glycols or any other known carrier used for pharmaceutical preparations. The latter may be in solid form, for example, as capsules, tablets, dragees and the like, or in liquid form, for example, as solutions, suspensions, emulsions and the like. If desired, they may contain auxiliary substances, such as preserving, stabilizing, wetting, emulsifying, coloring, flavoring agents and the like, salts for varying the osmotic pressure, buffers, etc. They may also contain, in combination, other useful substances.
The 3-(amino-phenyl)-2-(pyridyl)-acrylonitrile compounds of this invention, having the formula in which Py and Am have the previously-given meaning, or the salts thereof, may be prepared, for example, by treating a pyridyl-acetonitrile of the formula in which Py has the previously-given meaning, with an amino-benzaldehyde, of the formula Am-C H CHO, in which Am has the previously-given meaning, and, if desired, converting a resulting salt into the free compound or into another salt, and/or, if desired, converting a resulting compound into a salt thereof, and/or, if desired, separating a mixture of isomers into the single isomers.
The above reaction is carried out according to known methods; preferably, it is performed in the presence of a base, such as, for example, an alkali metal lower alkanolate, e.g. lithium, sodium or potassium methanolate, ethanolate, n-butanolate, tertiary butanolate and the like, a strong quaternary ammonium hydroxide, e.g. benzyl trimethyl ammonium hydroxide and the like, or any other equivalent basic reagent, e.g. piperidine and the like, and of a suitable inert solvent, e.g. methanol, ethanol and the like, if necessary, while cooling or at an elevated temperature, in a closed vessel, and/or in the atmosphere of an inert gas, e.g. nitrogen and the like.
Compounds of this invention may also be prepared by converting in a compound having the formula in which Py has the previously given meaning, or a salt thereof, the nitro group into the desired amino group Am by reduction, and, if desired, carrying out the optional steps.
Conversion of the nitro group into amino carried out according to known methods, for example, by treating the starting material with a reducing reagent, such as a metal (iron, tin and the like) in the presence of an acid (hydrochloric, sulfuric acid and the like), catalytically activated hydrogen (hydrogen in the presence of Raney nickel, platinum oxide and the like, under controlled conditions), or any other suitable reducing reagent. A nitro' group may be converted into an N-lower alkylamino or an N,N-di-lower alkyl-amino group by reductive alkylation, for example by carrying out the reduction, particularly with catalytically activated hydrogen, in the presence of an aldehyde (e.g. formaldehyde and the like) or a ketone. Methods for the reduction of a nitro group into an amino group Am are referred to by Wagner and Zook, Synthetic Organic Chemistry, p. 653 (Wiley, 1953).
The starting material used in the above precedure is prepared according to known methods, such as, for example, one of the previously mentioned procedures.
A salt resulting from one of the above procedures may be converted into the free base according to known methods, for example, by treatment with an alkaline reagent, such as an alkali metal hydroxide, e.g. lithium hydroxide, sodium hydroxide, potassium hydroxide and the like, an alkali metal carbonate, e.g. sodium or potassium carbonate or hydrogen carbonate and the like, ammonia, or any other suitable reagent, such as a hydroxyl ion exchange preparation and the like.
A resulting salt may be converted into another salt, for example, by reacting the former with an inorganic salt of an inorganic or organic acid, such as a silver, sodium and the like, salt of such acid, or with a suitable anion exchange preparation.
A free base may be converted into a salt according to known methods, for example, by treating a solution of the base in an inert solvent or solvent mixture with the appropriate acid, such as one of the above-mentioned inorganic or organic acids, if desired, a solution thereof in an inert solvent or solvent mixture, and isolating the desired salt. Salts may be isolated in the form of hydrates.
Resulting mixtures of isomers may be converted into the single isomers according to known methods. For example, racemates may be resolved into the optically active dand l-forms, for example, by treating a racemic mixture, preferably in solution with an inert solvent or solvent mixture, with one of the optically active forms of an acid containing an asymmetric carbon atom, or a solution thereof, and isolating the resulting salt. Especially useful as optically active forms of salt-forming acids having an asymmetric carbon atom are D-tartaric (l-tartaric) acid of L-tartaric (d-tartaric) acid; the optically active forms of rhalic, mandelic, camphor-lO-sulfonic, quinic acid and the like, may also be used. A resulting salt may be converted into the free and optically active base according to process as outlined hereinbefore, and an optically active base may be converted into an acid addition salt or a quaternary ammonium compound, according to the previously-mentioned methods. Mixtures of other isomers, e.g. diastereoisomers, are separated on the basis of physicochemical differences, e.g. solubility and the like.
The invention also comprises any modification of the process wherein a compound obtainable as an intermediate at any stage of the process is used as starting material and the remaining step(s) of the process is(are) carried out, as well as any new intermediates.
This is a continuation-in-part application of my application Serial No. 165,324, filed January 110, 1962, now abandoned.
The following examples are intended to illustrate the invention and are not to be construed as being limitations thereon. Temperatures are given in degrees centigrade.
Example 1 To a solution of 6.0 g. of 4-N,N-dimethylaminobenzaldehyde and 6.0 g. of (3-pyridyl)-acetonitrile in 20 ml. of methanol is added approximately 0.1 g. of sodium methanolate while stirring. Within five minutes, the reaction mixture solidifies and is diluted with Water. The solid material is filtered off and washed with water to yield the desired 3-(4-N,N-dimethylaminophenyl)-2-(3-pyridyl) -acrylonitrile of the formula which is recrystallized from aqueous ethanol and a mixture of ethyl acetate and pentane, M.P. 142-143.
Other 3 (amino-phenyl)-2-(pyridyl)-acrylonitriles, such as 3-(4-arnino-phenyl)-2-(3-pyridyl)-acrylonitrile, 3-(4-N-methyl-amino=phenyl)-2-(2 pyridyl) acrylonitrile, 3 (3 -N,N-dimethylamino-phenyl)-2-(4-pyridyl)- acrylonitrile and the like, may be prepared according to the above procedure.
Example 2 To a solution of 3.0 g. of (4-pyridyl)-acetonitrile in 15 ml. of percent ethanol is added a solution of 3.7 g. of 4-N,N-diyethylamino-benzaldehyde in 10 ml. of 95 percent ethanol while stirring. Small portions of solid sodium methanolate are added until a precipitate is formed, and the mixture solidifies. Water is added, the yellow solid is filtered off and is recrystallized from a mixture of ethanol and water to yield 2.8 g. of 3-(4-N,N-dimethylamino)-2-(4-pyridyl)-acrylonitrile of the formula which melts at l81l82.
Example 3 To a solution of 2.5 g. of 3-(4-nitro-phenyl)-2-(4-pyridyl)-acrylonitrile in ml. of p-dioxane is added 1.0 g. of a palladium catalyst (5 percent palladium on charcoal), and the mixture is treated with hydrogen at atmospheric pressure. After the uptake of the theoretical amount of hydrogen, the hydrogenation is interrupted, the catalyst is filtered off and the filtrate is evaporated to dryness. The yellow solid is recrystallized from ethanol to yield the desired 3-(4-amino-phenyl)-2-(4-pyridyl)- acrylonitrile of the formula which melts at 224-227".
The starting material used in the above reaction is prepared as follows: To a solution of 3.0 g. of (4-pyridyl)-acetonitrile and 3.8 g. of 4-nitro-benzaldehyde in 95 ethanol are added while stirring small portions of solid sodium methanolate until the solution begins to darken. During the exothermic reaction a solid material precipitates, the reaction mixture is diluted with Water, and the solid material is filtered olf. The desired 3-(4-nitrophenyl) -2-(4-pyridyl) acrylonitrile melts at 199-200 after recrystallization from ethanol.
What is claimed is:
1. A member selected from the group consisting of a compound of the formula in which Py is pyridyl, and Am is a member selected from the group consisting of amino, N-lower alkyl-arnino and N,N-di-lower alkyl-amino, and a pharmaceutically acceptable, non-toxic acid addition salt thereof.
2. 3-(4-N,N-dimethy1a.mino-phenyl) 2 (3-pyridy1)- References Cited in tha file of this patent acrylonitrile.
3. 3- 4 N,N dimethylamino-phenyl)-2-(4-pyridy1)- UNITED STATES PATENTS acrylonitflle, 2,567,245 Sperber et a1. Sept. 11, 1951 4. 3-(4-amino-phenyl)-2-(4-pyridyl)-acry1onitrile. 5 2,727,895 Sperber et a1. Dec. 20, 1955

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1. A MEMBER SELECTED FROM THE GROUP CONSISTING OF A COMPOUND OF THE FORMULA
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US20090308670A1 (en) * 2008-06-17 2009-12-17 The Board Of Trustees Of The University Of Alabama Hybrid dinghy pusher
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US7662461B2 (en) 2006-03-31 2010-02-16 Milliken & Company Synthetic leather articles and methods for producing the same
US20070231546A1 (en) * 2006-03-31 2007-10-04 Jusong Xia Synthetic leather articles and methods for producing the same
US7872069B2 (en) 2006-03-31 2011-01-18 Milliken & Company Coated substrates and polymer dispersions suitable for use in making the same
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US8431648B2 (en) 2006-03-31 2013-04-30 Milliken & Company Coated substrates and polymer dispersions suitable for use in making the same
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US20080113198A1 (en) * 2006-11-10 2008-05-15 Jusong Xia Leather articles and methods for producing the same
US20080229519A1 (en) * 2007-03-20 2008-09-25 Karel Jozef Maria Depoot Liquid treatment composition
US20090308670A1 (en) * 2008-06-17 2009-12-17 The Board Of Trustees Of The University Of Alabama Hybrid dinghy pusher
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