DD236310A1 - PROCESS FOR PREPARING 2,6-DIARYL SUBSTITUTED 4-ARYLAMINO-PYRIMIDIN-5-CARBOXYLIC ACID ESTERS - Google Patents

Abstract

The invention relates to a process for the preparation of 2,6-diaryl-substituted 4-arylamino-pyrimidine-5-carboxylic acid esters. It is the object of the invention to produce these previously unknown compounds. The task is to find a technically feasible synthetic route. The object is achieved by the reaction of 2-cyano-3-aryl-3-thioaroylamido acrylic acid esters with arylamines. The compounds obtained are of pharmaceutical interest.

Description

wherein R ¹ , R ² and R ^{3 have} the meaning given above, are reacted.

Field of application of the invention

The invention relates to a process for the preparation of 2,6-diaryl-substituted 4-arylamino-pyrimidine-5-carboxylic acid esters. Such compounds may gain importance for the preparation of pharmaceuticals.

Characteristic of the known technical solutions -

2,6-diaryl-substituted 4-arylamino-pyrimidine-5-carboxylic acid esters are hitherto unknown. 4-Arylamino-pyrimidine-5-carboxylic acid esters with other substituents in the 2- and 6-position are described in the literature. They can be obtained by reacting the corresponding 4-halo-pyrimidine-5-carboxylic acid esters with aromatic amines. (JA Barone, E. Peters, H. Tieckelmann, J. Org Chem 24, 198 (1959); K. Grohe, H. Heitzer, Liebigs Ann. Chem., 1973, 1025; PF Juby, TW Hudyma, FRG Off VK Karp, VA Portnyagina, IS Barkova, Khim, Geterotsikl Soedin 1977, 1252, ref .: CA 88, 22827 (1978); HK Dong, A. Santilli, AR Fieber, J. Heterocycl. Chem. 1972, 1347). This process has the disadvantage that the starting compounds required for this purpose are only accessible in low yield or via a complicated synthetic route or only 4-arylamino-pynmidine-5-carboxylic acid esters having a specific substituent pattern can be prepared.

Object of the invention

The aim of the invention is to produce such compounds from readily available starting materials in a simple manner.

Explanation of the essence of the invention

The object of the invention is to produce 2,6-diaryl-substituted 4-arylamino-pyrimidine-5-carboxylic acid esters from readily available starting compounds in a technically applicable synthesis route. According to the invention this object is achieved in that 2-cyano-3-aryl-3-thioaroylamido-acrylic acid ester of the type II,

WC i

j C S

Il

where R ^{1 is} an alkyl radical (C ₁ to C ₆ ) - and R ^{2 is} a substituted or unsubstituted aryl radical, with arylamines of the type IH ₂ NR ³ IM

wherein R ^{3 represents} a substituted or unsubstituted aryl radical, to the 2,6-diaryl-substituted 4-arylamino-pyrimidine-5-carboxylic acid ester of type I,

R ² -

wherein R ', R ² and R ^{3 have} the meaning given above, are reacted. The invention will be explained in more detail below by exemplary embodiments.

example 1

Compound I with R '= C ₂ H ₅ and R ² = R ³ = C ₆ H ₅ (meaning always parts by weight) The mixture of 1 part II (R' = C ₂ H ₅ , R ² = C ₆ H ₆ ) and 0.28 part III (R ³ = C ₆ H ₅ ) in 20 parts of methyl glycol is allowed to stand at room temperature for 7 days. Subsequently, 6 parts of water are added. The precipitate is sucked off. This gives 0.62 parts (52%) of the product, which has a melting range of 99-105 ⁰ C (acetonitrile).

Example 2

Compound I with R ¹ = C ₂ H ₅ , R ² = C ₆ H ₅ and R ³ = C ₆ H ₄ (m) CH ₃ 0.32 part III (R ³ = C ₆ H ₄ (m) CH ₃ ) are reacted analogously to Example 1. This gives 0.40 parts (33%) of the product, which has a melting range of 107-113 ° C (gasoline.

Example 3

Compound I with R ¹ = C ₂ H ₅ , R ² = C ₆ H ₅ and R ³ = C ₆ H ₄ (p) OCH ₃ 0.37 parts III (R ³ = C ₆ H ₄ (p) OCH ₃ ) are reacted analogously to Example 1. This gives 0.67 parts (53%) of the product, which has a melting range of 150-151 ° C (acetonitrile).

Example 4

Compound I with R '. = C ₂ H ₅ , R ² = C ₆ H ₅ and R ³ = C ₆ H ₄ (p) OH 0.33 part III (R ³ = C ₆ H ₄ (p) OH) implemented analogously to Example 1. This gives 0.42 parts (34%) of the product, which has a melting range of 155-161 ⁰ C (benzene / gasoline).

Example 5

Compound I with R ¹ = C ₂ H ₅ , R ² = C ₆ H ₅ and R ³ = C ₆ H ₄ (p) Cl The mixture of 1 part II (R ¹ = C ₂ H ₅ , R ² = C ₆ H ₅ ) and 0.38 part III (R ³ = C ₆ H ₄ (p) Cl) in 20 parts of methyl glycol is allowed to stand at room temperature for 7 days. The precipitate is sucked off. This gives 0.80 parts (62%) of the product, which has a melting range of 144-145 ° C (acetonitrile).

Example 6

Compound I where R '= C ₂ H _5, R ² = C ₆ H ₅ and R ³ = C ₀ H ₇ (naphth-1-yl) 0,43Teile III (R ³ = C ₁₀ H ₇₎ (Napht- 1-ylamine) are reacted analogously to Example 5. This gives 0 ^ 56 parts (42%) of the product, which has a melting range of 160-161 ⁰ C (benzene / gasoline).

Example 7

Compound I with R ¹ = C ₂ H ₅ , R ² = C ₆ H ₄ (m) CH ₃ and R ³ = C ₆ H ₄ (P) OCH ₃ The mixture of 1 part II (R ¹ = C ₂ H ₅ R ² = C ₆ H ₄ (rn) CH ₃ ) and 0.33 part III (R ³ = C ₆ H ₄ (p) OCH ₃ ) in 3 parts of methyl glycol is allowed to stand at room temperature for 2 days. The precipitate is sucked off. This gives 0.57 parts (46%) of the product, which has a melting range of 97-103 ⁰ C (acetonitrile).

Example 8

Compound I with R ¹ = C ₂ H ₅ , R ² = C ₆ H ₄ (P) CH ₃ and R ³ = C ₆ H ₄ (P) OCH ₃ 1 part II (R ¹ = C ₂ H ₅ , R ² = C ₆ H ₄ (p) CH ₃ ) is reacted analogously to Example 7. This gives 0.57 parts (46%) of the product, which has a melting range of 153-156 ⁰ C (acetonitrile).

Example 9

Compound I with R ¹ = C ₂ H ₅ , R ³ = C ₆ H ₄ (P) OCH ₃ and R ³ = C ₆ H ₄ (P) OCH ₃ 1 part II (R ¹ = C ₂ H ₅ , R ² = C ₆ H ₄ (p) OCH ₃ ) is reacted analogously to Example 7. This gives 0.44 parts (36%) of the product, which has a melting range of 159-160 ° C (acetonitrile).

Example 10

Compound I with R ¹ = C ₂ H ₅ , R ² = C ₆ H ₄ (p) Cl and R ³ = C ₆ H ₄ (P) OCH ₃ 1 part II (R ¹ = C ₂ H ₅ , R ² = C ₆ H ₄ (p) Cl) is reacted analogously to Example 7. This gives 0.74 parts (60%) of the product, which has a melting range of 150-156 ° C (acetonitrile).

Claims (2)

- I - UYiY T Invention claim: A process for the preparation of 2,6-diaryl-substituted 4-arylamino-pyrimidine-5-carboxylic acid esters, characterized in that 2-cyano-3-aryl-3-thioaroylamido-acrylic ester of type II, NC COOP / CS II Il where R ^{1 is} an alkyl radical (C, to C ₆ ) - and R ^{2 is} a substituted or unsubstituted aryl radical, with arylamines of the type IH ₂ NR ³ IM where R ^{3 represents} a substituted or unsubstituted aryl radical, to the 2,6-diaryl-substituted 4-arylaminopyrimidine-5-carboxylic acid esters of type I,