MXPA99006217A - PREPARATION OF ACYLATED&agr;-AMINO CARBOXYLIC ACID AMIDES - Google Patents
PREPARATION OF ACYLATED&agr;-AMINO CARBOXYLIC ACID AMIDESInfo
- Publication number
- MXPA99006217A MXPA99006217A MXPA/A/1999/006217A MX9906217A MXPA99006217A MX PA99006217 A MXPA99006217 A MX PA99006217A MX 9906217 A MX9906217 A MX 9906217A MX PA99006217 A MXPA99006217 A MX PA99006217A
- Authority
- MX
- Mexico
- Prior art keywords
- aminonitrile
- carboxylic acid
- acylated
- aqueous solution
- amide
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title description 5
- 125000005219 aminonitrile group Chemical group 0.000 claims abstract description 24
- 150000001266 acyl halides Chemical class 0.000 claims abstract description 10
- 150000001408 amides Chemical class 0.000 claims abstract description 9
- 150000002825 nitriles Chemical class 0.000 claims abstract description 3
- 230000003301 hydrolyzing Effects 0.000 claims abstract 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- 239000002585 base Substances 0.000 claims description 7
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 230000000875 corresponding Effects 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
- XGISHOFUAFNYQF-UHFFFAOYSA-N pentanoyl chloride Chemical group CCCCC(Cl)=O XGISHOFUAFNYQF-UHFFFAOYSA-N 0.000 claims description 4
- BGTOWKSIORTVQH-UHFFFAOYSA-N Cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 claims description 3
- 238000005917 acylation reaction Methods 0.000 claims description 3
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 238000010992 reflux Methods 0.000 claims description 3
- 239000011541 reaction mixture Substances 0.000 claims description 2
- 238000005755 formation reaction Methods 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 238000001914 filtration Methods 0.000 abstract description 4
- 238000003436 Schotten-Baumann reaction Methods 0.000 abstract description 3
- 239000002244 precipitate Substances 0.000 abstract 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea Chemical class NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 15
- -1 ester hydrochloride Chemical class 0.000 description 8
- 239000002253 acid Substances 0.000 description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
- 238000006460 hydrolysis reaction Methods 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- 150000001263 acyl chlorides Chemical class 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- XPXMKIXDFWLRAA-UHFFFAOYSA-N hydrazinide Chemical class [NH-]N XPXMKIXDFWLRAA-UHFFFAOYSA-N 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N methylene dichloride Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N n-butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000002194 synthesizing Effects 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- ZMANZCXQSJIPKH-UHFFFAOYSA-N triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 2
- YGVGITVCEHRBDK-UHFFFAOYSA-N 1-aminocyclopentane-1-carboxamide Chemical compound NC(=O)C1(N)CCCC1 YGVGITVCEHRBDK-UHFFFAOYSA-N 0.000 description 1
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Natural products CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 1
- 102000005862 Angiotensin II Human genes 0.000 description 1
- 229950006323 Angiotensin ii Drugs 0.000 description 1
- 101800000733 Angiotensin-2 Proteins 0.000 description 1
- 208000008787 Cardiovascular Disease Diseases 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II dizwitterion Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 1
- NUJOXMJBOLGQSY-UHFFFAOYSA-N Manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 206010038435 Renal failure Diseases 0.000 description 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Substances CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001348 alkyl chlorides Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 230000003042 antagnostic Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 125000004432 carbon atoms Chemical group C* 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- 125000003074 decanoyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(*)=O 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 125000000268 heptanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 125000000400 lauroyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910000468 manganese oxide Inorganic materials 0.000 description 1
- YZTQKMVBEGUONQ-UHFFFAOYSA-N manganese(4+) Chemical compound [Mn+4] YZTQKMVBEGUONQ-UHFFFAOYSA-N 0.000 description 1
- AMWRITDGCCNYAT-UHFFFAOYSA-L manganese(II,III) oxide Inorganic materials [Mn].O[Mn]=O.O[Mn]=O AMWRITDGCCNYAT-UHFFFAOYSA-L 0.000 description 1
- QDHHCQZDFGDHMP-UHFFFAOYSA-N monochloramine Chemical compound ClN QDHHCQZDFGDHMP-UHFFFAOYSA-N 0.000 description 1
- 125000001419 myristoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- 125000001402 nonanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002801 octanoyl group Chemical group C(CCCCCCC)(=O)* 0.000 description 1
- 125000002811 oleoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])/C([H])=C([H])\C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000003389 potentiating Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 125000003696 stearoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 230000000033 vasopressor Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Abstract
A method of preparing acylated&agr;-amino carboxylic acid amides directly from aminonitriles in high yield and purity. The method involves acylating the aminonitrile with an acyl halide under Schotten-Baumann conditions, and hydrolyzing the resulting nitrile to the amide. The resulting acylated amino carboxylic acid amide precipitates and can be isolated by filtration in high purity.
Description
PREPARATION OF AMIDAS ACILADAS OF THE ACID ALPHA-AMINO CARBOXILICO
Field of Invention
The present invention relates to processes for producing acylated amides of α-amino carboxylic acid. Such amides are useful as intermediates for heterocyclic N-substratified pharmaceutical compositions useful in the treatment of cardiovascular disorders including hypertension, or glaucoma, diabetic retinopathy and renal insufficiency. In particular, the pharmaceutical compositions demonstrate antagonistic action against angiotensin II, a potent vasopressor.
Background of the Invention
Conventional processes for the preparation of the a-amino carboxylic acid amides suffer from several disadvantages, including low yields, low purity, the requirements of many steps in the synthetic route, and complex isolation schemes. Ref .: 30218 Thus, a route for the amides is described in Abramov, et al., Zhurnal Orgna. Khimii, 20 (7), pages 1243-1247 (1984) where the preparation of the a-aminoamides and a-amino acids is taught from the corresponding α-aminoni tory using manganese (IV) in the form of manganese oxide . Reaction times are critical, since longer reaction times lead to the amino acid. Additionally, a reversion may occur for the starting cyanohydrin and ketone.
Other somewhat analogous synthetic schemes are described in Johnson, et al., J. Org. Chem. 27, pages 798-802 (1962). This method involves the reaction of an aminonitrile with anhydrous HCl in the presence of an alcohol. The aminonitrile is dissolved in n-butanol and then treated with anhydrous HCl and stirred at room temperature for 24 hours. The reaction mixture is then refluxed for one hour. The immediate ester hydrochloride is formed as an intermediate, and is decomposed with the application of heat to the corresponding amide and an alkyl chloride.
U.S. Patent No. 5,352,788 discloses a synthesis involving hydrolysis of the oxalate salt of aminonitrile using concentrated sulfuric acid, followed by treatment with ammonia and then extracting with chloroform containing 5% methanol.
Conventional synthesis routes for the acylated amides of α-amino carboxylic acid involve acylating the amide, such as cycloleucine amide, with acyl chloride in THF with triethylamine. However, this is desirable to eliminate the use of organic solvents and to provide a simple, inexpensive process for preparing acylated amines of a-amino carboxylic acid directly from the amino nitrile.
It is therefore an object of the present invention to provide a method for producing acylated aminoamides directly from the corresponding amino nitrile.
It is a further object of the present invention to provide a method for producing acylated aminoamides from amino nitriles in high yields and without the concomitant production of potentially hazardous co-products.
It is still yet another object of the present invention to provide a method for producing acylated aminoamides from amino nitriles are the required complex isolation steps.
Description of the invention.
The problems of the prior art are then overcome by the present invention, which provides a method for preparing α-amino carboxylic acid amides acylated directly from amino nitriles in high and pure product. The method involves acylating the amino nitrile with an acyl halide, preferably acyl chloride, under Schotten-Baumann conditions. The resulting acylated amine-carboxylic acid amine can be hydrolyzed, precipitated and isolated by filtration in high purity.
Detailed description of the invention
The amino nitrile can be virtually any a-amino-nyl ryl corresponding to the acylated amine of a-amino carboxylic acid, and can be prepared from the corresponding ketone or aldehyde by conventional means well known to those skilled in the art. For example, the ketone in an appropriate solvent such as methanol, can react with a source of ammonia (such as ammonia and ammonium chloride) and a source of cyanide (such as alkali metal cyanide), and the resulting amino nitrile can be coated by Extraction with methylene chloride and drying. Dialkyl aminonitriles such as acetone aminonitrile, acetophenone aminonitrile, methyl ethyl aminonitrile are suitable, are as monoalkyl aminoni trils such as banzaldehyde aminonitrile and acetonide aldehyde. N-subsituted amino acids are also suitable, including N-methyl glycononitrile, N-butyl aminonitrile and N-phenyl aminonitrile. Cyclopentanone aminonitrile is particularly preferred.
Suitable acyl groups for the acyl halide are straight or branched aliphatic or aromatic groups containing from 1 to 40 carbon atoms, preferably acyl group which are carboxylic acid derivatives. Examples of preferred acyl groups are valeroyl, pentanoyl, hexanoyl, heptanoyl, octanoyl, nananoyl, decanoyl, lauroyl, myristoyl, palmitoyl, oleoyl, stearoyl, nonanoyl, neopent, anilyl, neohethylene, neodecanoyl, iso-oct, anilyl, iso-nananoyl. , isotridecanoi, benzoyl and naphthoyl. Varyl chloride is particularly preferred.
In accordance with the present invention, the pH of an aqueous amino nitrile solution is adjusted within a range of 9-12 (standard Schotten-Baumann conditions) to effect acylation, and the temperature is maintained between about 0 and 30 °. C, preferably around 10 ° C. The amino nitrile can be used slightly in excess for the acid halide, preferably 1.05 or less / 1.00. Excesses of amino nitrile are operable but excessive. The acyl halide is slowly added to the aqueous solution of amino nitrile in a range such that the average temperature of the reaction is stored up to 20 ° C or lower. The average pH of the reaction is preferably maintained in the above range, more preferably in a range between 9.5-10.5, by co-feeding a base, preferably alkali metal hydroxide, to the reaction medium with the acyl halide. The base serves to purify the acid (HCl in the case of acyl chloride) generated from the acylation and thus maintaining the pH within the operable range. As a result, operable amounts of base may vary depending on the amount of acid generated, but are generally between 1-2 times the number of equivalents of acid halide. The failure to co-feed the base with the acyl halide results in the hydrolysis of the acyl halide as a complete reaction.
Preferably, the reaction is stirred at 20 ° C and then maintained for at least two hours while the pH is maintained within the aforementioned range. The hydrolysis is then carried out by adjusting the pH, preferably to at least about 0.5 with an appropriate acid, such as HCl, sulfuric or phosphoric acid, preferably HCl, to hydrolyze the nitrile to the carboxylic acid amide. Higher pHs in the range of 0.5-4 can be used, but result in longer reaction times. Alternatively, the hydrolysis can be conducted under basic conditions, such as with the addition of 0.1 to 4 equivalents of alkali metal hydroxide. The reaction is then heated to reflux to completely affect the hydrolysis of the carboxylic acid nitrile. Temperatures of 30-100 ° C are appropriate, with the highest end of the range being preferred in order to minimize reaction times. The hydrolysis is generally completed in two hours. The resulting solids (amino acylated carboxylic acid amide) are isolated and can be collected by filtration.
The theoretical reaction mechanism can be illustrated as follows by the preparation of the cycloleucine valerate amide:
Example 1
The amino nitrile of cyclopentanone is prepared using methods commonly found in the literature. The amino nitrile of cyclopentanone (30.00 g, 0.273 mol) and water are added to a 5-necked 5-necked round bottom flask equipped with a mechanical stirrer, a pH meter, a thermometer, and two additional funnels. The pH is then adjusted to 10.00 with 50% NaOH and the reaction is cooled to 10 ° C. Valeryl chloride (31.60 g, 0.262 mol) is then slowly added to the reaction at a range such as to maintain the temperature at 20 ° C or less. The pH of the reaction is maintained from 9.5-10.5 by co-feeding 25% NaOH (10.91 g, 0.272 mol) to the reaction with valeryl chloride. The reaction was stirred at 20 ° C for one hour maintaining the pH of 9.5-10.5 with 25% NaOH. After one hour, the pH was adjusted to 0.5 with concentrated HCl, the reaction was heated to reflux for one hour, cooled to room temperature, and the resulting solids were collected by filtration.
E jem lo 2.
The aminonitrile was acylated as previously described on a scale of 0.455 moles. 0.437 moles of NaOH (50% aqueous) was then added and the reaction was warmed to 70 ° C for ten hours. The resulting solution contained approximately 50% conversion to the cycloleucine valerate amide.
It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.
Having described the invention as above, the content of the following is claimed as property.
Claims (9)
1. A process for preparing an acylated amide of a-amino carboxylic acid, characterized in that it comprises: preparing an aqueous solution of a-aminonitrile; acylating the a-aminonitrile in the aqueous solution by adding an acyl halide and sufficient base to the aqueous solution to maintain the pH of the aqueous composition in the range of 9-12; and hydrolyzing the resulting acylated nitrile for the corresponding carboxylic acid amide by adjusting the pH of the aqueous solution in the range of 0-4 under reflux, the amide being precipitated from the aqueous solution in formation.
2. The process of claim 1, characterized in that the a-aminonitrile is selected from the group consisting of aminoni triles dialkyl, aminoni trilos monoalquilo and aminonit rilos N-subs tu tiidos.
3. The process of claim 1, characterized in that the α-aminonitrile is aminonitrile cyclopentanone.
4. The process of claim 1, characterized in that the acyl halide is valeryl chloride.
5. The process of claim 3, characterized in that the acyl halide is valeryl chloride.
6. The process of claim 1, characterized in that it additionally comprises lowering the pH of the reaction mixture to at least about 0.5 to complete the acylation reaction.
7. The process of claim 1, characterized in that the base is an alkali metal hydroxide.
8. The process of claim 1, characterized in that the base is sodium hydroxide.
9. The process of claim 1, characterized in that the pH is adjusted in the range of 0-4 with hydrochloric acid.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08783924 | 1997-01-17 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA99006217A true MXPA99006217A (en) | 2000-01-01 |
Family
ID=
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5284972A (en) | N-acyl-N,N',N'-ethylenediaminetriacetic acid derivatives and process of preparing same | |
| US5849950A (en) | Preparation of glycine-N,N-diacetic acid derivatives | |
| US3979449A (en) | Preparation of an asparagine or a glutamine | |
| CA2497062A1 (en) | Preparation of amino acid amides | |
| JP5536087B2 (en) | Method for producing iodinated contrast agent | |
| US5763661A (en) | Preparation of acylated α-amino carboxylic acid amides | |
| JP3440129B2 (en) | Method for producing glutamine derivative | |
| JP3054163B2 (en) | Phosphinic acid ester-containing N-acyl-2-amino acid amide, process for producing the same and N-acyl-2-amino acid nitrile as precursor | |
| MXPA99006217A (en) | PREPARATION OF ACYLATED&agr;-AMINO CARBOXYLIC ACID AMIDES | |
| US5068416A (en) | Preparation of β-alaninediacetic acid or its alkali metal or ammonium salts | |
| JP5618306B2 (en) | Novel synthesis of substituted 4-amino-pyrimidines | |
| AU728197B2 (en) | Preparation of alpha-amino carboxylic acid amides | |
| US5530159A (en) | Preparation of α-alaninediacetic acid or its alkali metal or ammonium salts | |
| WO2022169747A1 (en) | Method for preparing levetiracetam and intermediates thereof | |
| SU526285A3 (en) | The method of obtaining derivatives of 3-and / or 2-butenoic acid | |
| US20220324801A1 (en) | Method for preparing levetiracetam and intermediates thereof | |
| JPH0114226B2 (en) | ||
| CA2570255A1 (en) | 4-t-butylgabapentin and its synthesis | |
| JPS62178556A (en) | Manufacture of alpha-amino-alpha-hydrogen-carboxylic acid amide | |
| JPH09301941A (en) | Production of n-long-chain acylamino acid and its salt | |
| JP2001163845A (en) | Method of producing amino acid amide | |
| JPH0468304B2 (en) | ||
| FR2508037A1 (en) | ||
| WO2010058577A1 (en) | Method for producing unsaturated aminocarboxylic acid derivative | |
| JP2002088047A (en) | Method for producing n-substituted cyanoglycine alkyl ester |