Process for the preparation of enantiomeric forms of 2,3-diaminopropionic acid derivatives

1. A process for obtaining a compound of formula III or a salt thereof:

wherein R1 is a hydrogen atom, F, Cl, I, Br, (C 1 -C 4 )-alkyl or —CN;

and R2 is a heteroaryl residue selected from the series consisting of pyrrole, furan, thiophene, imidazole, pyrazole, oxazole, isoxazole, thiazole, isothiazole, tetrazole, 1,2,3,5-oxathiadiazole-2-oxides, triazolones, oxadiazolone, isoxazolone, oxadiazolidinedione, triazole, 3-hydroxypyrrole-2,4-diones, 5-oxo-1,2,4-thiadiazoles, pyridine, pyrazine, pyrimidine, indole, isoindole, indazole, phthalazine, quinoline, isoquinoline, quinoxaline, quinazoline, cinnoline and β-carboline, wherein the heteroaryl residue is unsubstituted or is substituted once, twice or three times, independently of each other, by substituents selected from the series consisting of (C 1 -C 5 )-alkyl, (C 1 -C 5 )-alkoxy, halogen, nitro, amino, trifluoromethyl, hydroxy, hydroxy-(C 1 -C 4 )-alkyl-, methylenedioxy, ethylenedioxy, formyl, acetyl, cyano, hydroxycarbonyl-, aminocarbonyl- and (C 1 -C 4 )-alkoxycarbonyl-, or an aryl residue selected from the series consisting of phenyl, naphthyl, 1-naphthyl, 2-naphthyl, biphenylyl, 2-biphenylyl, 3-biphenylyl, 4-biphenylyl, anthryl and fluorenyl, wherein the aryl residue is unsubstituted or is substituted once, twice or three times, independently of each other, by substituents selected from the series consisting of (C 1 -C 5 )-alkyl, (C 1 -C 5 )-alkoxy, halogen, nitro, amino, trifluoromethyl, hydroxy, hydroxy-(C 1 -C 4 )-alkyl-, methylenedioxy, ethylenedioxy, formyl, acetyl, cyano, hydroxycarbonyl-, aminocarbonyl- and (C 1 -C 4 )-alkoxycarbonyl-;

R5 is —NH 2 , —N(H)-R6 or —N(R6) 2 , wherein R6 is (C 1 -C 4 )-alkyl or aryl, wherein the aryl residue is selected from the series consisting of phenyl, naphthyl, 1-naphthyl, 2-naphthyl, biphenylyl, 2-biphenylyl, 3-biphenylyl, 4-biphenylyl, anthryl and fluorenyl;

said process comprising

a) mixing a compound of formula II:

wherein R1 and R2 are as defined above, and R3 is a hydrogen atom,

or (C 1 -C 4 )-alkyl,

or an aryl residue selected from the series consisting of phenyl, naphthyl, 1-naphthyl, 2-naphthyl, biphenylyl, 2-biphenylyl, 3-biphenylyl, 4-biphenylyl, anthryl and fluorenyl, wherein the aryl residue is unsubstituted or is substituted, independently of each other, once, twice or three times by substituents selected from the series consisting of —NO 2 , —O—(C 1 -C 4 )-alkyl, F, CI and Br,

or —O—C(CH 3 ) 3 ,

or —O—CH(R7)-aryl, wherein the aryl residue is selected from the series consisting of phenyl, naphthyl, 1-naphthyl, 2-naphthyl, biphenylyl, 2-biphenylyl, 3-biphenylyl, 4-biphenylyl, anthryl and fluorenyl and is unsubstituted or is substituted, independently of each other, once, twice or three times by substituents selected from the series consisting of —NO 2 ,—O—CH 3 , F, Cl and Br, and wherein R7 is a hydrogen atom or (C 1 -C 4 )-alkyl;

in an organic solvent or a mixture of organic solvents with an enantiomerically pure auxiliary;

b) separating the salt composed of enantiomerically pure auxiliary and compound of formula I:

by fractional crystallization;

c) isolating the compound of formula I from the salt composed of enantiomerically pure auxiliary and compound of formula I;

d) converting the resulting compound of formula I with ammonia or an amine of the formula H 2 N-R6 or HN(R6) 2 , wherein R6 is (C 1 -C 4 )-alkyl or aryl, wherein the aryl residue is selected from the series consisting of phenyl, naphthyl, 1-naphthyl, 2-naphthyl, biphenylyl, 2-biphenylyl, 3-biphenylyl, 4-biphenylyl, anthryl and fluorenyl, into a compound of formula IV:

or a salt thereof; and

e) converting the resulting compound of formula IV or salt thereof into the compound of formula III or a salt thereof.

2. The process as claimed in claim 1 , wherein a compound of formula III or a salt thereof is obtained, wherein

R1 is a hydrogen atom, F, CI, I or Br;

R2 is phenyl, pyridinyl, pyrimidinyl or thiazolyl, wherein phenyl, pyridinyl, pyrimidinyl and thiazolyl are unsubstituted or substituted by fluorine or chlorine;

R5 is —NH 2 , —N(H)-R6 or —N(R6) 2 , wherein R6 is (C 1 -C 4 )-alkyl or aryl, wherein the aryl residue is selected from the series consisting of phenyl, naphthyl, 1-naphthyl, 2-naphthyl, biphenylyl, 2-biphenylyl, 3-biphenylyl, 4-biphenylyl, anthryl and fluorenyl.

3. A compound of formula III, selected from the series consisting of (S)-2-amino-3-(phenyl-pyrimidin-2-ylamino)-propanoic acid amide (formula IIIa), or a salt thereof, and (R)-2-amino-3-(phenyl-pyrimidin-2-ylamino)-propanoic acid amide (formula IIIb), or a salt thereof: