DD279016A1 - PROCESS FOR PREPARING 6-CHLORO-3-CYAN-2-DIMETHYLAMINO-METHYLENAMINO-5- (PYRID-4-YL) -PYRIDINE - Google Patents

Abstract

The invention relates to a process for preparing 6-chloro-3-cyano-2-dimethylaminomethyleneamino-5- (pyrid-4-yl) -pyridine by reacting 2-amino-5- (pyrid-4-yl) -nicotinic acid nitrile 1-oxide with POCl3 in DMF as a solvent. Areas of application of the invention are the pharmaceutical and the agrochemical industry.

Description

Field of application of the invention

The invention relates to a process for the preparation of e-chloro-S-cyan ^ -dimethylaminomethylenamino-S-ipyrid ^ -yO-pyridine Jer formula I.

The compound has significance as an intermediate for the production of biologically active substances, in particular of pharmaceuticals and pesticides.

The invention is applicable in the pharmaceutical and agrochemical industry.

Characteristic of the known state of the art

2-Amino-3-cyano-5- (pyrid-4-yl) -pyndine as well as 6-alkyl-2-amino-3-cyano-5- (pyrid-4-yl) -pyridines are known.

Also described are 6-unsubstituted and 6-methyl-substituted 2-alkylamino-3-cyaii-5- (pyrid-4-yl) -pyridines

(G.Y. Lesher et al., US Pat. No. 4,362,734) and corresponding 2 oxaalkylamino or 2-aminoalkylamino derivatives (Hagen, V. et al.

EP-PS 0200024). .

It is generally known that pyridine-N-oxides can be converted into 2-chloro-pyridines by reaction with POCl ₃ (see, for example, US Pat.

E. Ochiai: Aromatic Amine Oxides. [19671). Frequently here are Vilsmeier-Haack conditions, d. H. For example, the presence of DMF necessary. In the case of 2-amino-pyridine N-oxides, reactions under these conditions may be expected at the amino group. JL Miesel (US Patent 4508722) describes the formation of 6-chloro-5- (4-chloro-phenyl) -2-formamido-3-pyridinecarboxylic acid ethyl ester in the reaction of the corresponding 2-amino-N-oxide with POCl3 / DMF.

J. B. Neilsen et al. (Heterocycl J. Chem., 24, 1621 j 1987]) obtained in the Dosoxychlorierung of 2-amino-3-cyano-5-phenylpyrazin-1-oxide under Vilsmeier-Haack conditions e-chloro-S-cyan ^ -Dimethylaminomethylenamino -S-phenyl-pyrazine, while EC Taylor et al. (J. Organ. Chemistry 40,2341 [1975]) showed that under similar conditions 2-amino-3-cyano-5-methyl-pyrazine-1-oxide 2-amino-6-chloro-3-cyano-6 Methyl pyrazine is formed.

6-Chloro-3-cyano-2-dimethylaminomethyleneamino-5- (pyrid-4-yl) -pyridine is not known.

Object of the invention

It is the object of the invention to make available for the production of new biologically active substances harmful 6-chloro-3-cyano-2-dimethylaminomethyleneamino-5- (pyrid-4-yl) -pyridine, starting from easily accessible starting materials should.

Explanation of the nature of the invention

The invention has for its object to develop an ancestor for the preparation of 6-chloro-3-cyano-2-dimethylaminomethylenamino-5- (pyrid-4-yl) pyridine.

According to the invention this object is characterized g host that 2-amino-5- (pyrid-4-yl) -nicotinsäurenitril-1-oxide of the formula II with

POCl ₃ in rjmethylformamid (DMF) at 60-95 ⁰ Ca or preferably at 75-95 ⁰ C is reacted and the formed 6-chloro-3-cyano-2-dimethyiaminmethylenamino-5- (pyrid-4-yl) pyridine after pouring the Reaction solution in water by immediate

Neutralization with bases we obtained J.

The process of the present invention makes it possible to prepare hitherto undescribed e-chloro-S-cyano-dimethylaminomethyleneamino-5- (pyrid-4-yl) -pyridine in a simple manner and with high purity.

The compound shown is a valuable intermediate for the synthesis of biologically active compounds, e.g. B. those with cardiotonic activity.

The invention will be explained in more detail below with reference to an embodiment.

embodiment

example 1

e-Chloro-S-cyano ^ -dimethylaminomethylenamino-S-fpyrid ^ yo-pyridine

to 4.24 g (20 mmol) of 2-amino-3-cyano-5- (pyrid-4-yl) -nicotinsäurenitrll-1-oxide in 40 ml of DMF are added dropwise at 80-95 ° C 6.4ml POCl ₃ with stirring and cooling , It is stirred for 5 min. At 80-95 ⁰ C, poured onto ice water and immediately neutralized with dilute NaOH. The precipitate is filtered off, dried, dissolved in CHCl ₃ , mixed with silica gel, filtered, concentrated, filtered off with suction and recrystallized from butyl acetate.

C ₁₄ H ₁₂ N ₅ Cl, (285.7). M .: 211-214 ⁰ C

C, 58.85 H, 4.23 N, 24.51, Cl, 12.41

gef. C, 59.02, H, 4.31, N, 24.66, Cl, 12.24

Yield: 3.27 g (57.2% of theory).

Claims (4)

1. A process for the preparation of e-chloro-S-cyano-dimethyl-aminomethyleneamino-6-pyridyl) -pyridine of the formula I, characterized in that 2-amino-5- (pyrid-4-yl) -nicotinsäurenitril-1-oxide is reacted with POCl ₃ in DMF. 2. The method according to claim 1, characterized in that DMF is used both as a reactant and as a solvent. 3. The method according to claim 1, characterized in that the reaction with POCl ₃ at temperatures of 60-95 ⁰ C, preferably at 75-95 ⁰ C. 4. The method according to claim 1, characterized in that the reaction mixture is neutralized immediately after pouring into ice water.