DEY0000127MA - - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY

Registration date: December 23, 1954 Made famous on September 20, 1956

GERMAN PATENT OFFICE

PATENT APPLICATION

CLASS 12q GROUP 601 INTERNAT. CLASS C 07 c-

Y127IVb / 12q

Michimasä Izumi, Oita (Japan)

has been named as the inventor

Yoshitomi Pharmaceutical Industries, Ltd., Osaka (Japan)

Representative: Dr.-Ing. A. von Kreisler, Dr.-Ing. K. Schönwald, Dipl.-Chem. Dr. phil. H. Siebeneicher and Dr.-Ing. Th. Meyer, patent attorneys, Cologne 1

Process for the preparation of N-substituted aminocarboxylic acid esters

The priority of the application in Japan of December 25, 1953 has been claimed

By the method according to the invention are N - bis - (/ J-chloroethyl) -aminocarbonsäureester ι following general formula

, CH ₉ -CH ₉ -Cl

XH ₉ -CH ₉ -Cl

receive. In the formula, R denotes hydrogen or a lower alkyl group and R ₁ ■ denotes a lower alkyl group.

The free aminocarboxylic acid esters obtained by the process according to the invention are im general oily substances which are sparingly soluble in water and in benzene, ether and others. are soluble.

The aminocarboxylic acid esters give salts with inorganic or organic acids. The salts are soluble in water, acetone, methyl alcohol, ethyl alcohol, but are relatively sparingly soluble in ethyl acetate and chloroform in the cold and also sparingly soluble in ether and benzene.

609 619/406

Y 127 IYbIUq

The compounds prepared according to the invention are effective against malignant tumors and have a lower toxicity than previously known similar compounds.

The esters are obtained by esterifying N-bis (chloroethyl) aminocarboxylic acids or their derivatives with the following formula:

υ - c - n;

XH ₉ -CH ₉ -Cl

XH ₂ -CH ₂ -Cl

in which R denotes hydrogen or a lower alkyl group and Y denotes a carboxyl, carboxamide, nitrile or carboxylic acid halide group which can be converted into carboxylic acid esters by esterification in a manner known per se.
If an aminocarboxylic acid is used as the starting material, the esterification can easily be carried out in the customary manner. If, on the other hand, an aminocarboxylic acid derivative is used, hydrolysis and esterification are carried out at the same time.

The compounds obtained are expediently isolated as salts. Of course you can they can also be obtained in unbound form. They are usually used for medical purposes in the form of salts.

Example ι

20 g of N-bis (/ S-chloroethyl) -glycinnitrile hydrochloride are heated with 120 ecm of alcoholic hydrochloric acid (30%) and 1.6 g of water on a water bath for 2 hours. The ammonium chloride which separates out after cooling is filtered off and the filtrate is distilled in vacuo. Yield: 19 g. Recrystallized from ethyl acetate, needle-shaped crystals of N-bis (/? - chloroethyl) - glycine ethyl ester hydrochloride are obtained. F. 115 ⁰ . Insoluble in ether and benzene, easily soluble in acetone, methanol, ethanol, sparingly soluble in ethyl acetate and chloroform. The picrate forms needle-shaped crystals that melt ^{at 89 to 90 0.}

B e ί s ρ i e 1 2

20 g of N-bis (/? - chloroethyl) -glycine hydrochloride are heated to 60 ° for about 6 hours with 100 cm of alcoholic hydrochloric acid (30%) and left to stand for one night. The solution is then ^{distilled at about 40 0} under reduced pressure. The crystals obtained in this way are recrystallized from ethyl acetate. Yield 15 g N-bis (/ J-chloräthy ^ -glycine ethyl ester hydrochloride. F. 115 ^0th

Example 3

log N-bis - (/? - chloroethyl) -alaninamide-hydrochlo-

R ₁ OOC-CN;

, CH ₉ -CH ₉ -Cl

XH ₉ -CH ₉ -Cl

R. CH ₂ -CH ₂ -Cl Y- -C-N: ..ι,.
H CH ₂ -CH ₂ -Cl

rid are heated to 60 ° for 8 hours with 100 ecm of alcoholic hydrochloric acid (30%) in a water bath. * The ammonium chloride which has separated out is filtered off. The filtrate is distilled under reduced pressure. Yield 3 g of N-bis (/? - chloroethyl) alanine ethyl ester hydrochloride. The picryl sulfonate melts at 157 to 158 ⁰ .

Example 4

10 g of N ^ bis (/ 3-chloroethyl) glycine amide hydrochloride are heated to 60 ° for 8 hours with 100 ecm of alcoholic hydrochloric acid (30%). The precipitated ammonium chloride is filtered off and the filtrate is distilled in vacuo. Recrystallization from acetone gives 5 g of N-bis (/? - chloroethyl) glycine ethyl ester hydrochloride. F. 113 ⁰ .

Claims (1)

PATENT CLAIM: Process for the preparation of N-substituted aminocarboxylic acid esters of the general formula in which R is hydrogen or a lower alkyl group and R _{1 is} a lower alkyl group, characterized in that compounds of the general formula in which R is hydrogen or a lower alkyl group and Y is a carboxylic acid, carboxamide, Carboxylic acid nitrile or Cafbonsäurehalogenid group means, in per se known Way converted into carboxylic acid ester.