GB587244A - Improvements relating to the synthesis of amino acid derivatives and salts thereof - Google Patents
Improvements relating to the synthesis of amino acid derivatives and salts thereofInfo
- Publication number
- GB587244A GB587244A GB1399844A GB1399844A GB587244A GB 587244 A GB587244 A GB 587244A GB 1399844 A GB1399844 A GB 1399844A GB 1399844 A GB1399844 A GB 1399844A GB 587244 A GB587244 A GB 587244A
- Authority
- GB
- United Kingdom
- Prior art keywords
- methyl
- hydroxy
- alaninium
- ethyl
- ester
- 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
Links
- 150000003839 salts Chemical class 0.000 title abstract 3
- 150000003862 amino acid derivatives Chemical class 0.000 title 1
- 230000015572 biosynthetic process Effects 0.000 title 1
- 238000003786 synthesis reaction Methods 0.000 title 1
- -1 methylenedioxy Chemical group 0.000 abstract 25
- 125000004432 carbon atom Chemical group C* 0.000 abstract 17
- 125000004494 ethyl ester group Chemical group 0.000 abstract 11
- 239000002253 acid Substances 0.000 abstract 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 abstract 9
- 125000000217 alkyl group Chemical group 0.000 abstract 9
- 125000003545 alkoxy group Chemical group 0.000 abstract 5
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 abstract 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 abstract 4
- 229910052736 halogen Inorganic materials 0.000 abstract 4
- 150000002367 halogens Chemical class 0.000 abstract 4
- 238000000034 method Methods 0.000 abstract 4
- 150000001875 compounds Chemical class 0.000 abstract 3
- 150000002148 esters Chemical class 0.000 abstract 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 abstract 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 abstract 2
- 229910019142 PO4 Inorganic materials 0.000 abstract 2
- 125000002947 alkylene group Chemical group 0.000 abstract 2
- 229910052799 carbon Inorganic materials 0.000 abstract 2
- 150000001721 carbon Chemical group 0.000 abstract 2
- XWBDWHCCBGMXKG-UHFFFAOYSA-N ethanamine;hydron;chloride Chemical compound Cl.CCN XWBDWHCCBGMXKG-UHFFFAOYSA-N 0.000 abstract 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 abstract 2
- 229940049920 malate Drugs 0.000 abstract 2
- 229910052757 nitrogen Inorganic materials 0.000 abstract 2
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract 2
- 239000010452 phosphate Substances 0.000 abstract 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 abstract 2
- 229910021653 sulphate ion Inorganic materials 0.000 abstract 2
- XZXYQEHISUMZAT-UHFFFAOYSA-N 2-[(2-hydroxy-5-methylphenyl)methyl]-4-methylphenol Chemical compound CC1=CC=C(O)C(CC=2C(=CC=C(C)C=2)O)=C1 XZXYQEHISUMZAT-UHFFFAOYSA-N 0.000 abstract 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 abstract 1
- 101100295738 Gallus gallus COR3 gene Proteins 0.000 abstract 1
- 229910002651 NO3 Inorganic materials 0.000 abstract 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 abstract 1
- 235000004279 alanine Nutrition 0.000 abstract 1
- 125000001931 aliphatic group Chemical group 0.000 abstract 1
- 150000001350 alkyl halides Chemical class 0.000 abstract 1
- 125000005233 alkylalcohol group Chemical group 0.000 abstract 1
- 229910052782 aluminium Inorganic materials 0.000 abstract 1
- 239000004411 aluminium Substances 0.000 abstract 1
- 150000001408 amides Chemical class 0.000 abstract 1
- 150000001414 amino alcohols Chemical class 0.000 abstract 1
- SWLVFNYSXGMGBS-UHFFFAOYSA-N ammonium bromide Chemical compound [NH4+].[Br-] SWLVFNYSXGMGBS-UHFFFAOYSA-N 0.000 abstract 1
- 150000003868 ammonium compounds Chemical class 0.000 abstract 1
- 229940107816 ammonium iodide Drugs 0.000 abstract 1
- 150000001450 anions Chemical class 0.000 abstract 1
- 150000001540 azides Chemical class 0.000 abstract 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 abstract 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 abstract 1
- 125000005191 hydroxyalkylamino group Chemical group 0.000 abstract 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 abstract 1
- FEWJPZIEWOKRBE-LWMBPPNESA-N levotartaric acid Chemical compound OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 abstract 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 abstract 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- VDUIPQNXOQMTBF-UHFFFAOYSA-N n-ethylhydroxylamine Chemical compound CCNO VDUIPQNXOQMTBF-UHFFFAOYSA-N 0.000 abstract 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 abstract 1
- VMLAEGAAHIIWJX-UHFFFAOYSA-N propan-2-amine hydroiodide Chemical compound [I-].C(C)(C)[NH3+] VMLAEGAAHIIWJX-UHFFFAOYSA-N 0.000 abstract 1
- ISYORFGKSZLPNW-UHFFFAOYSA-N propan-2-ylazanium;chloride Chemical compound [Cl-].CC(C)[NH3+] ISYORFGKSZLPNW-UHFFFAOYSA-N 0.000 abstract 1
- 239000000376 reactant Substances 0.000 abstract 1
- 238000010992 reflux Methods 0.000 abstract 1
- 239000002904 solvent Substances 0.000 abstract 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/58—Radicals substituted by nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Phenalkyl compounds of general formula <FORM:0587244/IV/1> wherein R1 represents H or alkyl (1 to 2 carbon atoms), R2 represents alkyl (1 to 5 carbon atoms), R3 represents alkoxy or hydroxyalkylamino (1 to 5 carbon atoms), R4 and R5 each represent H, alkyl (1 to 2 carbon atoms) or alkoxy (1 to 5 carbon atoms), or R4 and R5 together are methylenedioxy, R6 represents H or halogen, n is either zero or 1 and X represents alkylene (2 to 5 carbon atoms of which at least 2 are in the direct chain connecting the nitrogen atom with the COR3 group), and salts thereof, are obtained by treating a secondary phenalkyl amino alcohol having at least 2 carbon atoms in the chain between the phenyl group and the nitrogen atom and with the OH- group attached to the carbon atom in said chain next the ring, with an aliphatic acid ester (3 to 6 carbon atoms) which acid is either substituted by halogen on a carbon atom at least once removed from the carboxy group, or which is an a b -unsaturated acid. Preferably, the reactants are dissolved in a mutual solvent, being refluxed after standing for at least 2 hours; and the desired amino-ester salt is isolated by adding an alkyl alcohol (1 to 5 carbon atoms) and a strong acid to the mixture after refluxing. Conversion of the foregoing esters to the corresponding amides is effected by customary methods, e.g. by treatment with an alkylolamine; advantageously, b -alanine derivatives are amidated by the Stoll method, viz., converting the ester to the corresponding azide, prior to treating with an alkylolamine. Specified compounds obtained according to the invention are: N - methyl - N - (b - hydroxy - b - phenyl) isopropyl b -alanine methyl ester hydrochloride, l - N - methyl - N - (b - hydroxy - b - phenyl) isopropyl b -alanine ethyl ester hydrochloride, N - methyl - N - (b - hydroxy - b - 2 : 5 - dimethoxyphenyl) ethyl b -alanine methyl ester hydrochloride, N - methyl - N - (b - hydroxy - b - 2 : 5 - dimethoxyphenyl) ethyl-b -alanine n-amyl ester hydrochloride, N - methyl - N - (g -carbomethoxypropyl - b - hydroxy - b - 2 : 5 - dimethoxyphenyl) ethylamine hydrochloride, N - methyl - N - (b - hydroxy - b - 2 : 5 - dimethoxyphenyl) ethyl - b - alanine hydroxy ethyl amide acid oxalate, N - methyl - N - (b - hydroxy - b - 3 : 4 - dimethoxyphenyl) ethyl-b -alanine methyl ester hydrochloride, N - methyl - N - (g - carbethoxypropyl - b - hydroxy - b - 3 : 4 - methylenedioxy - 6 - bromo - phenyl) isopropylamine hydrochloride, N - ethyl - N - (b - hydroxy - a - ethyl - b - p - tolyl) ethyl b -alanine-methyl ester hydroiodide, N-methyl-N-(b -hydroxy-b -2-methoxy-5-methyl phenyl) ethyl b -alanine hydrochloride, N-n-amyl-N-(g -hydroxy - g - 3 : 4 - diethoxyphenyl) propyl b -alanine methyl ester phosphate, N-ethyl-N-(e -carbethoxy - n - amyl - b - hydroxy - 4 - methoxy - phenyl) ethyl amine sulphate, N-methyl-N-(g -hydroxy-g -3-amyloxyphenyl) propyl b -alanine methyl ester malate. Many examples are given of the process. The Provisional Specification describes also compounds of general formula <FORM:0587244/IV/2> wherein A represents an anion corresponding to an acid, X represents alkylene (2 to 6 carbon atoms) of which at least 2 are in the direct chain connecting N and -CO-, n is an integer (1 to 5), R1 represents hydroxy or methoxy and alkyl (1 to 5 carbon atoms), R3 represents alkyl (1 to 5 carbon atoms), R4 represents H or alkyl (1 to 5 carbon atoms), R5 represents alkoxy (1 to 5 carbon atoms), R6 represents H or -OH, or alkoxy or alkyl (1 to 5 carbon atoms), R6 represents H, -OH, halogen or alkoxy or alkyl (1 to 5 carbon atoms) or R6 and R7 together represent methylenedioxy, and R8 represents H, halogen or alkyl (1 to 5 carbon atoms). Quaternary salts are obtained by treating the corresponding tertiary bases with alkyl halides or sulphates. Specified phenalkyl ammonium compounds are: N - methyl - N - phenethyl - b - alaninium ethyl ester bromide, N-methyl-N-(b -hydroxy-b -phenylisopropyl)-b -alaninium ethyl- and the corresponding methyl-ester chlorides, N-ethyl-N-(b -2 : 5-dimethylphenylisopropyl)-b -alaninium methyl ester chloride, methyl n-butyl-b - (2 - methyl - 5 - isopropylphenyl) - isopropyl-g -carbomethoxypropyl ammonium iodide, N-ethyl - N - benzyl - N - (b - 3 : 4 - dimethoxyphenylpropyl) - b - alaninium methyl ester chloride, N - methyl - N - (3 : 4 - dimethoxyphenethyl) - b - alaninium ethyl ester chloride, N-methyl-N-(2 : 5 - dimethoxyphenethyl) - b - alaninium ethyl ester chloride, N - methyl - N - homopiperonyl - b - alaninium ethyl ester acid oxalate, methyl-2 : 5-dimethoxyphenethyl - g - carbomethoxypropyl ammonium chloride, l-N-methyl-N-(b -hydroxy-b - 3 : 4 - dimethoxyphenyl) - ethyl - b - alaninium methyl ester chloride, d - N - methyl - N - (b - hydroxy-b -3 : 4-dimethoxyphenyl) isopropyl-b -alaninium methyl ester bromide, N-ethyl-N-methyl-N-(b -hydroxy-b -3 : 4-dimethoxyphenyl) isopropyl b -alaninium ethyl ester iodide, N,N-dimethyl-N-(b -hydroxy-b -3 : 4-dimethoxy-6-chlorophenylisopropyl) - b - alaninium methyl ester chloride, dimethyl-g -carbethoxypropyl-b -hydroxy-b -(3 : 4-methylenedioxy-6-bromophenyl) isopropyl ammonium iodide, N,N-diethyl-N-p-chlorophenethyl - b - alaninium ethyl ester chloride, N-methyl-N-n-propyl-N-(g -hydroxy-g - p - bromophenyl - n - propyl) - b - alaninium methyl ester chloride, N-n-amyl-N-(#s-hydroxy-#s - p - tolylbutyl) - b - alaninium methyl ester malate, l-N-methyl-N-(b -2-hydroxy-5-bromophenylheptyl) - b - alaninium ethyl ester d-tartrate, N-methyl-N-(a -3 : 4-dihydroxybenzyl-n-hexyl)-b -alaninium methyl ester sulphate, methyl - a - (3 - methoxy - 4 - hydroxy - 5 - bromobenzyl) - n - propyl, e - carbethoxy amyl ammonium acid phosphate, N-methyl-N-(3 : 4-dimethoxyphenethyl)-b -alaninium n-amyl ester acid oxalate, N - methyl - N - (4 - methoxy - 3 - chlorophenethyl) - b - alaninium - n - butyl ester chloride, methyl-2 : 3-dimethoxyphenethyl-a -methyl - b - carboisobutoxyethyl ammonium bromide, N - methyl - N - (b - 3 : 4 - dimethoxyphenylisopropyl) - b - alaninium, ethanolamide acid oxalate, N : N - dimethyl - N - (b - hydroxy - b - 3 : 4 - dimethoxyphenylethyl) - b - alaninium b -hydroxyisopropylamide chloride, N-n-butyl-N - (4 - methoxy - 3 - bromophenylisopropyl) - b - alaninium ethanolamide bromide, N-n-propyl-N - (b - methoxy - b - 4 - n - butylphenylethyl) - b - alaninium ethyl ester chloride, N-methyl-N-(#z - hydroxy - #z - 3 : 4 - diethoxyphenylhexyl)-b -alaninium methyl ester bromide, methyl-g -hydroxy - g - mesityl - n - propyl - b - methyl - b -carbomethoxy ethyl ammonium chloride, methyl-2 : 5-dimethylphenethyl-a -n-butyl-b -carbethoxy ethyl ammonium bromide, N - methyl-N-(b -methoxy-b -4-n-propoxyphenylethyl) - b - alaninium methyl ester bromide, methyl - 3 : 4 - dimethoxyphenethyl - #z - carbo - methoxy hexyl ammonium bromide, N-methyl-N-(2-methoxy-5-n-amylphenethyl)-b -aluminium methyl ester nitrate, g - (ethyl - 3 : 4 - dimethoxyphenethylamino) - butyric acid ethanolamide ethochloride, N-methyl-N-(b -4-hydroxy - 3 : 5 - diiodophenylisopropyl) - b - alaninium ethyl ester chloride, dimethyl-3-hydroxy-4-methoxy-6-iodophenethyl-g -carbomethoxy - n - propyl ammonium bromide, N - methyl - N - (p-hydroxyphenethyl) - b - alaninium ethyl ester chloride, N : N - dimethyl - N - (p - hydroxyphenethyl) - b - alaninium ethyl ester chloride. Many examples of the process are also included.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB1399844A GB587244A (en) | 1944-07-21 | 1944-07-21 | Improvements relating to the synthesis of amino acid derivatives and salts thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB1399844A GB587244A (en) | 1944-07-21 | 1944-07-21 | Improvements relating to the synthesis of amino acid derivatives and salts thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB587244A true GB587244A (en) | 1947-04-18 |
Family
ID=10033156
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB1399844A Expired GB587244A (en) | 1944-07-21 | 1944-07-21 | Improvements relating to the synthesis of amino acid derivatives and salts thereof |
Country Status (1)
| Country | Link |
|---|---|
| GB (1) | GB587244A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2786045A (en) * | 1953-01-21 | 1957-03-19 | Tee Pak Inc | Hydroxyacyl-amino acids and their polymers |
| US2886594A (en) * | 1954-12-27 | 1959-05-12 | Sterling Drug Inc | N-(2-carbamylalkyl)-aralkylamines |
| US3936492A (en) * | 1969-10-20 | 1976-02-03 | The Kendall Company | Monomeric emulsion stabilizers |
| EP0289070A1 (en) * | 1987-04-10 | 1988-11-02 | Duphar International Research B.V | Tertiary arylethyl amine derivatives having opiate-antagonistic activity |
| US5393788A (en) * | 1990-07-10 | 1995-02-28 | Smithkline Beecham Corporation | Phenylalkyl oxamides |
-
1944
- 1944-07-21 GB GB1399844A patent/GB587244A/en not_active Expired
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2786045A (en) * | 1953-01-21 | 1957-03-19 | Tee Pak Inc | Hydroxyacyl-amino acids and their polymers |
| US2886594A (en) * | 1954-12-27 | 1959-05-12 | Sterling Drug Inc | N-(2-carbamylalkyl)-aralkylamines |
| US3936492A (en) * | 1969-10-20 | 1976-02-03 | The Kendall Company | Monomeric emulsion stabilizers |
| EP0289070A1 (en) * | 1987-04-10 | 1988-11-02 | Duphar International Research B.V | Tertiary arylethyl amine derivatives having opiate-antagonistic activity |
| US5393788A (en) * | 1990-07-10 | 1995-02-28 | Smithkline Beecham Corporation | Phenylalkyl oxamides |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES516131A0 (en) | A PROCEDURE FOR THE PREPARATION OF NEW N- (4-PIPERIDINYL) BENZAMIDES. | |
| ES8307719A1 (en) | "PROCEDURE FOR PREPARING N-SUBSTITUTED AMIDO AMINO ACIDS". | |
| ATE229522T1 (en) | SUBSTITUTED OXIME DERIVATIVES APPLICABLE AS NEUROKININ ANTAGONISTS | |
| BR9608269A (en) | Hydrazone and olefin oxides substituted as neurokinin antagonists | |
| GB1164192A (en) | Tetrahydroisoquinolines and process for preparing them | |
| US3846427A (en) | 1-(phthalimido-alkyl)-1,2,3,4-tetrahydroquinazolinones and analogues thereof | |
| GB587244A (en) | Improvements relating to the synthesis of amino acid derivatives and salts thereof | |
| US2520264A (en) | Substituted 3, 1-benz-2, 3, 4, 5-tetrahydroazepines | |
| ES8801903A1 (en) | Cinnoline derivatives. | |
| GB1092921A (en) | Anthranilic acid derivatives | |
| US3423512A (en) | Treatment of emesis in mammals with substituted methylenedioxy benzamides | |
| US2759933A (en) | Derivatives of aralkylbenzoic acid | |
| US2844585A (en) | Quaternary ammonium alkylamino-benzoquinones | |
| GB1426514A (en) | Basic esters and process for the preparation thereof | |
| US2623045A (en) | N-(substituted-aminoethyl) 4-aminobenzoic acid diethylaminoethyl esters | |
| US2674615A (en) | 1-arylcycloalkane 1-thiocar-boxylates | |
| IT8621857A1 (en) | KINNAMYLAMINES, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS THAT CONTAIN THEM | |
| US2447195A (en) | Diamides of alkane dicarboxylic acids | |
| US2555917A (en) | N-(tertiary-aminoalkylmercaptoalkyl) diphenyl-acetamides and their preparation | |
| AT163197B (en) | Process for the production of new amines | |
| GB1201221A (en) | N-(tertiary amino-alkyl)-2-alkenyl (or alkynyl) oxy-benzamides and a process for the preparation thereof | |
| JPS6075464A (en) | Aminoisoquinolinium derivative and its preparation | |
| US3052684A (en) | 4-aryl-4-alkanoyloxy-n-cyano substituted piperidines | |
| FI60552C (en) | NYTT FOERFARANDE FOER FRAMSTAELLNING AV 2-AMINO-3,5-DIBROM-BENZYLAMINER | |
| GB997039A (en) | New polypeptide compounds |