Basf Aktiengesellschaft

Wolfgang Littmann

Joachim Paust

Hartmut Leininger

Hansgeorg Ernst

Wolfgang Bewert

Walter Trautmann

2-Amino-3-cyano-5-dialkoxymethylpyrazine derivatives of the general formula III ##STR1## where R.sup.1 and R.sup.2 are each hydrogen or a protective group usually employed for amino groups and R.sup.5 and R.sup.6 are each alkyl of 1 to 4 carbon atoms, or together form an ethylene or propylene radical which is unsubstituted or substituted by methyl, are prepared starting from a novel 3-halomethyl-5-dihalomethyl-2-aminopyrazine derivative of the formula IV ##STR2## where X is Cl or Br, via a novel intermediate of the general formula I ##STR3## where R.sup.3 is --CH.sub.2 --O--CO--CH.sub.3 (a), --CH.sub.2 OH (b), ##STR4## or --C.tbd.N (d) and R.sup.4 is --CHCl.sub.2 or --CHBr.sub.2 or, where R.sup.1 and R.sup.2 are each a protective group, R.sup.4 may furthermore be ##STR5##

Preparation of 2-amino-3-cyano-5-dialkoxymethylpyrazines and

.alpha.-(o-Chlorophenyl)-aminomethylene-.beta.-formylaminopropionitrile, process for its preparation by reacting a metal salt of .alpha.-formyl-.beta.-formylaminopropionitrile with a salt of o-chloroaniline in an aqueous medium, and use of the product to prepare the compound of the formula ##STR1## by reaction with acetamidine. The pyrimidine thus obtained is an intermediate for the preparation of vitamin B.sub.1.

.alpha.-(o-chlorophenyl)-aminomethylene-.beta.-formylaminopropionitrile

2-Amino-3,5-di-(halomethyl)-pyrazines of the general formula I ##STR1## where X is either chlorine or bromine, m and n may each be 0, 1, 2 or 3 and R.sup.1 and R.sup.2 are each hydrogen or a protective group or may furthermore be bonded to one another, in particular those compounds of the formula I in which m is 1 and n is 2 and/or R.sup.1 and R.sup.2 together form a phthaloyl radical, are useful intermediates for the pteridine building block of folic acid or folic acid analogs. They are obtained by a method in which a 2-amino-3,5-dimethylpyrazine of the general formula II ##STR2## is treated with a chlorinating or brominating agent and, where R.sup.1 and/or R.sup.2 are protective groups, these are, if desired, eliminated when the chlorination or bromination is complete.

2-amino-3,5-di-(halomethyl)-pyrazines and their preparation

An improved method of manufacture of 2-methyl-4-amino-5-formylaminomethylpyrimidine (II), wherein a N-substituted or unsubstituted .alpha.-aminomethylene-.beta.-formylaminopropionitrile (I) is reacted with acetamidine. Compound II is an intermediate for the manufacture of vitamin B.sub.1.

Growing community of inventors

Mannheim, Germany

Wolfgang Littmann