GB2024223A - Process for the preparation of N,N'-disubstituted 2- naphthaleneethanimidamides and intermediates used therein - Google Patents
Process for the preparation of N,N'-disubstituted 2- naphthaleneethanimidamides and intermediates used therein Download PDFInfo
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- GB2024223A GB2024223A GB7922870A GB7922870A GB2024223A GB 2024223 A GB2024223 A GB 2024223A GB 7922870 A GB7922870 A GB 7922870A GB 7922870 A GB7922870 A GB 7922870A GB 2024223 A GB2024223 A GB 2024223A
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- salt
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- hydrogen
- disubstituted
- alkyl
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- 229910052757 nitrogen Inorganic materials 0.000 title claims abstract description 13
- 238000000034 method Methods 0.000 title claims description 14
- LHYUMRWJTVKTPD-UHFFFAOYSA-N 2-naphthalen-2-ylethanimidamide Chemical class C1=CC=CC2=CC(CC(=N)N)=CC=C21 LHYUMRWJTVKTPD-UHFFFAOYSA-N 0.000 title claims description 6
- 239000000543 intermediate Substances 0.000 title description 6
- 238000002360 preparation method Methods 0.000 title description 3
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- 150000003973 alkyl amines Chemical class 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims description 12
- -1 imido ester salt Chemical class 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 6
- 150000002825 nitriles Chemical class 0.000 claims description 6
- 239000012458 free base Substances 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000000129 anionic group Chemical group 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 17
- LPCWDVLDJVZIHA-UHFFFAOYSA-N 2-naphthalen-2-ylacetonitrile Chemical compound C1=CC=CC2=CC(CC#N)=CC=C21 LPCWDVLDJVZIHA-UHFFFAOYSA-N 0.000 abstract description 4
- 125000000217 alkyl group Chemical group 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 3
- 238000006136 alcoholysis reaction Methods 0.000 abstract description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 239000011541 reaction mixture Substances 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- GTTGADPSPVSIJG-UHFFFAOYSA-N ethyl 2-naphthalen-2-ylethanimidate;hydrochloride Chemical compound Cl.C1=CC=CC2=CC(CC(=N)OCC)=CC=C21 GTTGADPSPVSIJG-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- ISAQFJCVYKEERB-UHFFFAOYSA-N 2-naphthalen-1-ylethanimidamide Chemical class C1=CC=C2C(CC(=N)N)=CC=CC2=C1 ISAQFJCVYKEERB-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 101100037762 Caenorhabditis elegans rnh-2 gene Proteins 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 150000002463 imidates Chemical class 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- DIEOESIZLAHURK-UHFFFAOYSA-N n-naphthalen-2-ylacetamide Chemical compound C1=CC=CC2=CC(NC(=O)C)=CC=C21 DIEOESIZLAHURK-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C15/00—Cyclic hydrocarbons containing only six-membered aromatic rings as cyclic parts
- C07C15/20—Polycyclic condensed hydrocarbons
- C07C15/24—Polycyclic condensed hydrocarbons containing two rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C239/00—Compounds containing nitrogen-to-halogen bonds; Hydroxylamino compounds or ethers or esters thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C241/00—Preparation of compounds containing chains of nitrogen atoms singly-bound to each other, e.g. hydrazines, triazanes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C257/00—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
- C07C257/04—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines without replacement of the other oxygen atom of the carboxyl group, e.g. imino-ethers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C257/00—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
- C07C257/04—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines without replacement of the other oxygen atom of the carboxyl group, e.g. imino-ethers
- C07C257/06—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines without replacement of the other oxygen atom of the carboxyl group, e.g. imino-ethers having carbon atoms of imino-carboxyl groups bound to hydrogen atoms, to acyclic carbon atoms, or to carbon atoms of rings other than six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C257/00—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
- C07C257/10—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines
- C07C257/14—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines having carbon atoms of amidino groups bound to acyclic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
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- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
An N,N'-disubstituted 2- naphthaleneethanimidamine salt is prepared by the conversion of a 2- naphthylacetonitrile into a novel alkyl 2-napthaleneethanimidate salt intermediate by alcoholysis, followed by treatment of the intermediate with an alkylamine. The products can have CNS activity.
Description
SPECIFICATION
Process for the preparation of N,N'-disubstituted 2-naphthaleneethanimidamides and intermediates used therein
The invention relates to a process for preparing N,N'-disubstituted 2-naphthaleneethanimidamide salts of formula
wherein R is C13 alkyl; R1 and R2 (which may be at any of positions 1 and 3 to 8 of the ring) are the same or different and are each hydrogen, chlorine, bromine, fluorine, hydroxy, C1 3 alkoxy or C1 3 alkyl; and Xis the anionic portion of a salt-forming acid.
U. S. Patent Specification No. 3,903,163 describes various N,N'-disubstituted 2- naphthaleneethanimidamides and their pharmaceutically acceptable salts as displaying central nervous system activity. The compounds are particularly useful as antidepressant and antianxiety agents. The active compound were prepared by reacting a 2-naphthylacetonitrile with a selected primary amine and primary ammonium ion. Alternatively, the acitve compounds were prepared by the reaction of the corresponding substituted naphthylacetamide with trialkyloxonium fluoroborate to prepare the N-alkyl substituted arylinitrilium fluoroborate salt. This was followed by the reaction of the fluoroborate salt with a primary alkylamine.Neither of these methods is entirely satisfactoryforthe production of large batches of material for commercial purposes.
According to the present invention, a compound of formula I is prepared in a step reaction. In the first step, a nitrile of formula II:
wherein R1 and R2 are as defined above, is converted into the corresponding imido ester salt of formula ill
wherein R1, R2 and X are as defined above and R3 is C1-8 alkyl (preferably C13 alkyl) by alcoholysis using an absolute alkanol of formula R3OH and an anhydrous acid of formula HX. In the second step, the imido ester salt is treated with excess anhydrous alkylamine of formula RNH2 (R is as defined above) to give the
N,N'-disubstituted naphthaleneethanimidamide salt (I).
The N,N'-disubstituted 2-naphthaleneethanimidamine salt may be separated by conventional procedures such as filtration or centrifugation. The free base may be prepared by neutralisation of the salt in an aqueous base. For example, the salt may be mixed with an equivalent molar amount of sodium hydroxide in, for example, water or excess aqueous sodium carbonate, after which the free base is separated by extraction with an organic solvent. The free base may then be converted to any desired pharmaceutically acceptable salt thereof. The salt or free base may also be further purified, if desired, by using conventional procedures such as washing or recrystallisation.
The present invention also provides the novel alkyl 2-naphthaleneethanimidate salts of formula III which serve as intermediates in the above reaction sequence. Particularly preferred compounds of formula Ill are those wherein R1 and R2 are both hydrogen and those in which there is one substituent, at the 1-3- or 4position of the naphthalene ring, most preferably 1-chloro.
In practising the first step of the process of the invention, the 2-naphthylacetonitrile is dissolved in a non-hydrolytic solvent, such as toluene, chloroform, or ether, and treated with the absolute alkanol which may be, for example, methyl alcohol, ethyl alcohol or propyl alcohol. Per equivalent of the nitrile, from about 1 to 1.4 equivalents of alcohol are usually used, with about 1.15 equivalents of alcohol being preferred.
An anhydrous strong acid of formula HX, generally a hydrogen halide such as hydrogen chloride or hydrogen bromide, is then added at such a rate that the reaction temperature does not exceed 40"C. The minimum reaction temperature is 0 C. The preferred temperature for carrying out this step of the reaction is between 0 and 30"C. At least one equivalent of acid is required for complete reaction and greater quantities may be added up to the saturation point without significantly affecting the reaction. The reaction is allowed to run until substantially all of the nitrile is converted to the imidate. This generally takes about 15 hours. The reaction may be monitored by thin layer chromatography and the disappearance of the starting nitrile is indicative of complete reaction.The imido ester salt (III) usually crystallises from the reaction mixture and may be collected by filtration. The reaction should not be run above atmospheric pressure since undesirable side reactions may take place which effect the purity of the product.
In the second step of the process according to the invention, the imido ester salt (III) is reacted with a selected anhydrous C13 alkylamine in an inert solvent such as methanol, ethanol or diemthylfuran. This step may be carried out in a pressurised vessel, if desired. The reaction is run for a time sufficient to convert substantially all of the imido ester salt to the final product. An excess of alkylamine, at least two equivalents over the starting nitrile of formula II, ensures satisfactory yields of product.
The following two Examples illustrate the process of the invention. In these Examples, R is methyl, R1 and R2 are each hydrogen, Rg is ethyl and Xis chlorine.
Example 1
Ethyl 2-naphthaleneethanimidate hydrochloride A reaction vessel was charged with 40.0 grams (0.239 mol.) or 2-naphthylacetonitrile,12.7 12.7 grams (0.274 mol.) of absolute alcohol, and 400 ml of toluene. The resulting mixture was cooled at 20C, and anhydrous hydrogen chloride was sparged in until the temperature reached 10 C. Atotal of 17.4 grams (0.477 mol.) of hydrogen chloride was added. After the addition was complete, the reaction mixture was stirred at 2 C to 10"C for about two hours. The cooling bath was removed, and the reaction mixture allowed to warm to room temperature. The reaction mixture was stirred overnight during which time a white solid formed until the mixture was a thick slurry. The excess hydrogen chloride was sparged out with a stream of nitrogen.The solid was filtered off, washed with toluene, air dried, and vacuum dried to yield 57.7 grams (97% yield) of the title intermediate. The melting point was found to be 202 - 204"C, although the imidate salt rearranges on heating to form 2-naphthylacetamide.
Elerrientat analysis showed carbon 67.3%, hydrogen 6.70% and nitrogen 5.62% compared to theoretical values of carbon 67.3%, hydrogen 6.46%, and nitrogen 5.16%.
Example 2
N,N'-Dimethyl 2-naphthaleneethanimidate hydrochloride
In a 100 ml. reaction vessel, equipped with a stirrer, a thermometer, a pressure-equalising adition funnel, and a reflux condenser fitted with a drying tube, 11.95 grams (0.048 mol.) of ethyl 2naphthaleneethanimidate hydrochloride were placed. A solution of 21.20 grams (0.683 mol.) of methylamine in 35 ml. of absolute ethanol was rapidly added to the reaction mixture. The temperature quickly rose to 65 C and dropped to about 30"C after all of the solution was added. The reaction mixture was kept between about 50-53"C for 21 hours. The reaction mixture was cooled to 2"C and the white crystalline product was filtered off.The product was wahed with toluene and dried to give 10.2 grams (85% yield) of the title compound. The crude product was recrystallised from absolute ethanol to yield 8.97 grams of the title compound. The melting point was 225.5 - 227"C.
Other novel substituted ester salt intermediates of formula Ill may be prepared using the general procedure in Example 1. These compounds are suitable for use in the process described above for the preparation of the corresponding N,N'-disubstituted 2-naphthaleneethanimidamide.
Examples of such intermediates are as follows:ethyl 1 -chloro-2-naphthaleneethan imidate hydrochloride ethyl 6-methoxy-2-naphthaleneethanimidate hydrochloride ethyl 6-methyl-2-naphthaleneethanimidate hydrochloride ethyl 3-methyl-2-naphthaleneethanimidate hydrochloride ethyl 1 -hydroxy-2-naphthaleneethanimidate hydrochloride ethyl 6-hydroxy-2-naphthaleneethanimidate hydrochloride
Claims (9)
1. A process for preparing an N,N'-disubstituted 2-naphthaleneethanimidamide salt of formula I:
wherein R is C1-3 alkyl; R1 and R2 are the same or different and are each hydrogen, chlorine, bromine, fluorine, hydroxy, Cur 3 alkoxy or C1-3 alkyl; and X is the anionic portion of a salt-forming acid, which comprises the steps of
(I) reacting a nitrile of formula II
wherein R1 and R2 are as defined above, with an absolute C1-8 alkanol and an acid of the formula HX, wherein Xis as defined above, at between 0 and 40 C, to give an imido ester salt of formula Ill
wherein R1, R2 and X are as defined above, and F3 is C1-8 alkyl; and
(2) reacting the imide ester salt with at least two equivalents of an anhydrous Cur 3 alkylamine at from 45 to 1200C.
2. A process according to claim 1 comprising the additional step of converting the salt of formula I to the corresponding free base.
3. A process according to claim 1 or claim 2 in which step (1) is conducted at between 0 and 30"C.
4. A process according to any preceding claim in which step (2) is conducted between 50 and 80"C.
5. A process according to claim 1 substantially as described in the Examples.
6. A compound of formula Ill as defined in claim 1.
7. A compound as claimed in claim 6 wherein R1 and R2 are each hydrogen.
8. A compound as claimed in claim 6 wherein R1 is in the 1-3-or 4-position and is other than hydrogen and R2 is hydrogen.
9. A compound as claimed in claim 8 wherein R1 is 1-chloro.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US92169078A | 1978-07-03 | 1978-07-03 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB2024223A true GB2024223A (en) | 1980-01-09 |
| GB2024223B GB2024223B (en) | 1982-07-14 |
Family
ID=25445831
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB7922870A Expired GB2024223B (en) | 1978-07-03 | 1979-07-02 | Process for the preparation of n,n'-disubstituted 2 - naphta - leneethan - imidamides and intermediates used therein |
Country Status (12)
| Country | Link |
|---|---|
| JP (1) | JPS559095A (en) |
| AR (1) | AR230619A1 (en) |
| BE (1) | BE877449A (en) |
| CA (1) | CA1130305A (en) |
| CH (1) | CH641764A5 (en) |
| DE (1) | DE2926828A1 (en) |
| DK (1) | DK273079A (en) |
| ES (1) | ES482113A1 (en) |
| FR (1) | FR2430414A1 (en) |
| GB (1) | GB2024223B (en) |
| IT (1) | IT1121792B (en) |
| NL (1) | NL7904774A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0119799A1 (en) * | 1983-03-11 | 1984-09-26 | E.I. Du Pont De Nemours And Company | Process for preparing dialkyl propanediimidate dihydrohalides |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5180379A (en) * | 1991-04-04 | 1993-01-19 | Minnesota Mining And Manufacturing Company | Electrode with pre-wired leads |
| JPH08293371A (en) * | 1995-04-20 | 1996-11-05 | Nippon Denki Factory Eng Kk | Ic socket |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR1434131A (en) * | 1964-07-31 | 1966-04-08 | Usines Rhone Poulenc Soc D | New acetamidine derivatives |
| GB1243186A (en) * | 1967-11-29 | 1971-08-18 | Orsymonde | Improvements in or relating to mandelamidine derivatives |
| ZA696719B (en) * | 1968-10-17 | 1971-04-28 | Lilly Co Eli | 13-manphthylacetamidine and salts thereof |
| FR2036973A1 (en) * | 1969-04-24 | 1970-12-31 | Orsymonde | |
| US3742000A (en) * | 1969-06-03 | 1973-06-26 | Grace W R & Co | Imidoether and amidine derivatives of substituted fatty amides |
| JPS5246949B2 (en) * | 1973-10-19 | 1977-11-29 | ||
| DD109864A1 (en) * | 1973-11-20 | 1974-11-20 | ||
| US3903163A (en) * | 1974-10-02 | 1975-09-02 | Dow Chemical Co | N,N-Disubstituted naphthaleneacetamidines |
| JPS5198201A (en) * | 1975-02-18 | 1976-08-30 | n22 chikan omega amijino arufua aminosanjudotaimataha sonosanfukaenno seizoho |
-
1979
- 1979-06-13 IT IT23509/79A patent/IT1121792B/en active
- 1979-06-19 NL NL7904774A patent/NL7904774A/en not_active Application Discontinuation
- 1979-06-28 DK DK273079A patent/DK273079A/en not_active Application Discontinuation
- 1979-06-29 FR FR7917017A patent/FR2430414A1/en active Granted
- 1979-06-29 CA CA330,828A patent/CA1130305A/en not_active Expired
- 1979-07-02 CH CH616579A patent/CH641764A5/en not_active IP Right Cessation
- 1979-07-02 GB GB7922870A patent/GB2024223B/en not_active Expired
- 1979-07-02 ES ES482113A patent/ES482113A1/en not_active Expired
- 1979-07-03 AR AR277173A patent/AR230619A1/en active
- 1979-07-03 JP JP8437179A patent/JPS559095A/en active Granted
- 1979-07-03 DE DE19792926828 patent/DE2926828A1/en not_active Ceased
- 1979-07-03 BE BE0/196104A patent/BE877449A/en not_active IP Right Cessation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0119799A1 (en) * | 1983-03-11 | 1984-09-26 | E.I. Du Pont De Nemours And Company | Process for preparing dialkyl propanediimidate dihydrohalides |
Also Published As
| Publication number | Publication date |
|---|---|
| FR2430414A1 (en) | 1980-02-01 |
| IT7923509A0 (en) | 1979-06-13 |
| JPS559095A (en) | 1980-01-22 |
| CH641764A5 (en) | 1984-03-15 |
| AR230619A1 (en) | 1984-05-31 |
| BE877449A (en) | 1980-01-03 |
| GB2024223B (en) | 1982-07-14 |
| CA1130305A (en) | 1982-08-24 |
| FR2430414B1 (en) | 1984-06-08 |
| ES482113A1 (en) | 1980-04-01 |
| DK273079A (en) | 1980-01-04 |
| DE2926828A1 (en) | 1980-01-17 |
| NL7904774A (en) | 1980-01-07 |
| IT1121792B (en) | 1986-04-23 |
| JPS6343382B2 (en) | 1988-08-30 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PCNP | Patent ceased through non-payment of renewal fee |
Effective date: 19930702 |