DE1116668B - Process for the preparation of pyridyl or quinolyl ketones of the 4-oxycoumarin series - Google Patents

Description

GERMAN

PATENT OFFICE

K27479IVd / 12p

REGISTRATION DATE: DECEMBER 1, 1955

NOTICE THE REGISTRATION DND OUTPUT EDITORIAL: NOVEMBER 9, 1961

The invention is concerned with the production of new pyridyl- or quinolyl- [4-oxy-coumarinyl- (3)] - ketones following constitution:

OH

R ₂ {

X \ / ^ | - CO - R ₁

C = O

. . "/ ίο

s / ο

where R _{1 represents} a substituted or unsubstituted pyridyl or quinolyl radical. R ₂ can mean H or various substituents, such as. B. - CH ₃ or - Cl.

Connections in this body class have not yet been established.

The surprising observation was made that this body class is light, comfortable according to the invention and in good yields by conversion of 4-oxycoumarin or one substituted in the benzene nucleus 4-oxycoumarin with a pyridine or quinoline carboxylic acid is accessible in the presence of phosphorus oxychloride. Instead of 4-oxycoumarin you can also use Derivatives of 4-oxycoumarins with substituents in the aromatic ring are used, such as. B. 6-chloro-4-oxycoumarin or 6-methyl-4-oxycoumarin. The present is a prerequisite for implementation of phosphorus oxychloride, which apparently plays the role of a catalyst.

Phosphorus oxychloride is described as a catalyst for ketone syntheses in the 4-oxycoumarin series (J. Klosa, Arch. Pharm., Ber. dtsch. pharmaz. Ges., Vol. 288, pp. 356 to 361 [1955]). The action of acetic acid on 4-oxycoumarin in Presence of phosphorus oxychloride 3-aceto-4-oxycoumarin can be obtained (Arch. Pharmaz., Ber. Dtsch. pharmacy Ges., Vol. 286, p. 42, para. 3 [1953]), but the transfer of this synthesis method to the implementation of benzoic acid or other carboxylic acids such as cyanoacetic acid, lactic acid and mandelic acid, does not lead to the desired ketones (J. Klosa, Arch. Pharmaz., Ber. German pharmacy Ges., Vol. 289, pp. 104 to 110 [1956]. Cinnamic acid also results in this Investigation not the expected ketone. Since now the pyridine carboxylic acids on the one hand solid substances with are high melting points and, on the other hand, are subject to numerous tautomerisms, so that too the 1 position of the pyridine is able to react as an imino group, it was not to be expected that [pyridyl] - [4-oxy-coumarinyl- (3)] - ketones would result would form, especially in manufacturing processes

of pyridyl or quinolyl ketones

the 4-oxycoumarin series

Applicant:

Dipl.-Chem. Dr. Josef Klosa,
Berlin-Zehlendorf, Jänickestr. 13th

Dipl.-Chem. Dr. Josef Klosa, Berlin-Zehlendorf,
has been named as the inventor

an analogous ketone formation has never been known to pyridine chemistry.

Representatives of the new class of bodies produced according to the invention have some interesting pharmacodynamic ones Properties; so is [pyridyl- (β)] - [4-oxycumarinyl- (3)] - ketone in a dilution of 1: 5000 Up to 1: 10,000 hyperaemic effective. This hyperaemic effect lasts for about 30 to 60 minutes. The effect thus differs from that of the strongly and persistently hyperaemic pyridine-3-carboxylic acid esters (see, for example, German Patent 839 036) by a short duration; also are the new products insoluble in water. The [pyridyl- (4)] - [4-oxy-coumarinyl- (3)] - ketone unfolds on the other hand an anticoagulant effect that sets in quickly (about the same speed as with dicumarinyl acetic acid ethyl ester) and is also long-lasting and uniform, so that a trough-like curve results.

Representatives of the present new group of compounds are said to be used as remedies or as intermediates for remedies Find use.

The production of the new body class according to the invention is explained using an exemplary embodiment:

example
[Pyridyl- (| S)] - [4-oxy-cumarmyl- (3)] - ketone

5 g of 4-oxycoumarin are triturated with 7 to 8 g of nicotinic acid and 15 to 20 ml of phosphorus oxychloride are added. An immediate reaction sets in with strong evolution of hydrogen chloride and warming, see above that initially it is cooled until the warming subsides. After the main reaction has subsided, is taking the reaction mixture on the water bath

109 738/400

Heated to reflux for a further 15 to 30 minutes. The result is a slightly mobile, brownish liquid which, after cooling, is poured into 5 times the amount of ice water while stirring. There are pale brown needles which, after dissolving in a little alcohol and adding water, give colorless needles. M.p .: 91 to 93 ⁰ C. Yield: 85 to 90%.

The following are obtained analogously:

2. [Pyridyl- (y)] - [4-oxycumarinyl- (3)] - ketone, m.p .: 102 to 104 ⁰ C,

3. [Pyridyl - («)] - [4-oxycumarinyl- (3)] - ketone, m.p .: 97 to 99 ° C,

4. [6-methyl-pyridyl- (2)] - [4-oxycumarinyl- (3)] - ketone, m.p .: 87 to 89 ⁰ C, 15

5. [quinolyl - ( ")] - [4-oxycumarinyl- (3)] - ketone, m.p .: 96 to 98 ⁰ C,

6. [quinolyl (y)] - [4-oxycumarinyl- (3)] - ketone, m.p .: 98 to 100 ⁰ C,

7. [Pyridyl - («)] - [4-oxy-6-chloro-coumarinyl- (3)] - 20 ketone, m.p .: 156 to 58 ° C,

8. [PyridyK ^ - ^ - oxy-o-chloro-coumarinyHS)] - ketone, m.p .: 140 ⁰ C,

9. [Pyridyl- (y)] - [4-oxy-6-chloro-coumarinyl- (3)] - ketone, M.p .: 160 to 162 ° C, 25

10. [3-Methyl-pyridyl- (2)] - [4-oxy-6-chloro-coumarinyl- (3)] - ketone, m.p .: 161 to 163 ° C,

11. [Pyridyl- (a)] - [4-oxy-6-methyl-coumarinyl- (3)] - ketone, M.p .: 116 to 118 ° C,

12. pyridyl - (/?)] - [4-oxy-6-methyl-coumarinyl- (3)] - ketone, M.p .: 117 to 19 ° C,

13. Pyridyl- (y)] - [4-oxy-6-methyl-coumarinyl- (3)] - ketone, M.p .: 120 to 122 ° C,

14. [6-Methyl-pyridyl- (2)] - [4-oxy-6-methyl-coumarinyl- (3) 3-ketone, M.p .: 115 to 117 ° C.

Claims (1)

Claim: Process for the preparation of pyridyl or quinolyl ketones of the 4-oxycoumarin series, characterized in that a pyridine or quinolinecarboxylic acid in the presence of phosphorus oxychloride with 4-oxycoumarin or a 4-oxycoumarin substituted in the benzene nucleus, such as 4- Oxy-6-chloro-coumarin or 4-oxy-6-methyl-coumarin. Publications considered: Arch. D. Pharmazie, Vol. 286, p. 42 (1953). © 109 738/400 10.61