DD293820A5 - PROCESS FOR THE PREPARATION OF 3-HYDROXY-3- (2-ACETAMINO) -THIEN-3-YL] ACRYLIC ACID ESTERS AND NITRILES - Google Patents

Abstract

The invention relates to a process for the preparation of * and -nitriles of the general formula I, wherein R 1 is R 2 alkyl, polymethylene; R 3 R 4 alkoxycarbonyl, cyano, acetyl, phenyl mean. These compounds are potential drugs and at the same time intermediates of the pharmaceutical industry. The object of the invention is, starting from 2-aminothiophene-3-carboxylic acids of the general formula III, in which R 1 R 2 denotes alkyl, polymethylene, by reaction with acetic anhydride * of the general formula II in which R <1> R <2> denote alkyl, polymethylene and then prepare these by reaction with C-H acidic structures in compounds of the general formula I in which R <1>, R <2>, R <3> and R <4> have the above significance {Pharmacy; Synthesis; Substitution; Drug development; thiophene carboxylic acids; acrylate; acrylonitriles; *}

Description

embodiments

The invention will be explained below with reference to the following embodiment:

example

Preparation of 3-hydroxy-2-methoxycarbonyl-3-t (2-acetamino-4,5-tetramethylene) -thien-3-yl] -acrylic Acid Methyl Ester

0.006 mol of NaH and 0.006 mol of dimethyl malonate are stirred in 20 ml of dry DMF for 30 minutes until the evolution of hydrogen has ended. After addition of the 2-methyl-5,6-tetramethylene-thieno [2,3-d] [1,3] oxazin-4-one, the reaction mixture is stirred for about 2 hours. Subsequently, 1 ml of methanol is added dropwise and the reaction solution is poured into 50 ml of water. After neutralization with dilute HCl, the mixture is filtered off with suction and crystallized from methanol or ethanol.

C ₁₆ H ₁₉ NO ₆ S (353.4) Melting range: 187-19O ⁰ C; Yield: 76%

In an analogous manner, the compounds of general structure I listed below in the table are shown:

table

R ¹ R ²

- (CH ₂ I ₄ -

CH ₃ CH ₃

- (CHj) ₄ - (CHj) ₄ -

CH ₃ CH ₃

- (CHj) ₄ -

CH ₃ CH ₃

- (CHj) ₄ - - (CHj) ₄ -

^RJ R ' to hum formula COOC ₂ H ₅ COOC ₂ H ₆ C ₁₈ H ₂₃ NO ₆ S COOCH ₃ COOCH ₃ C ₁₄ H ₂₃ NO ₆ S COOCH ₃ CN Ci ₆ H ₁₆ N ₂ O ₄ S COOC ₂ H ₆ CN C ₁₆ H ₁₈ N ₂ O ₄ S COOCH ₃ CN C ₁₃ H ₁₄ N ₂ O ₄ S CN CN C ₁₄ H ₁₃ N ₃ O ₂ S CN CN C ₁₂ H ₁₁ N ₃ O ₂ S CN COCH ₃ C ₁₇ H ₂₂ NO ₆ S CN C ₆ H ₆ C ₁₉ H ₂₃ NO ₄ S

mol Schmb. yield Dimensions CO (%) 381.4 156-160 37 327.4 170-173 82 320.4 234-237 62 334.4 228-231 66 294.3 240-244 34 287.3 210-212 62 261.3 215-218 71 352.4 125-128 42 361.4 118 (dec.) 29

Formula sheet

Forme ?! I i

Shaped ?! ill

hormel I

OH

, R ~

II> R ^J - R ^v - alkyl, polymet.hyIen

R ³ - R ⁴ = alkoxycarbonyl 1, cyano, acetyl, phenyl

R · ¹

R ¹ = R ^a = alkyl, polymethylene

r COOH

F \ ^lj - = R ^M = alkyl, polymethyl len

Claims (3)

A process for the preparation of 3-hydroxy-3 - [(2-acetamino) -thien-3-yl] -acrylic acid esters and nitriles of general formula I wherein R ¹ = R ² = alkyl, polymethylene R ³ = R ⁴ = alkoxycarbonyl, cyano, acetyl, phenyl mean, characterized in that first 2-aminothiophene-3-carboxylic acids of general formula III wherein R ¹ = R ² = alkyl, polymethylene mean, with acetic anhydride to compounds of general formula II, wherein R ¹ = R ² = alkyl, polymethylene mean, cyclized and then these 2-methyl-thieno [2,3-d] [1,3] oxazin-4-ones by reaction with CH-acidic structures in compounds of general formula I are transferred. For this 1 page formulas Field of application of the invention The invention relates to a process for the preparation of 3-Hydroxy-3 - [(2-acetamino) thien-3-yl-acrylic acid esters and nitriles, wherein R ¹ = R ² = alkyl, polymethylene R ³ = R ⁴ = alkoxycarbonyl, cyano, acetyl, phenyl mean. Compounds of the general formula I represent potential drugs and at the same time intermediates of the pharmaceutical industry. Characteristic of the known state of the art Compounds of the general formula I have hitherto been described more wildly in the patent literature, but in the literature comparative reactions of 4H-3,1-benzoxazin-4-ones with N-containing dianions are reported (F. Clemence et J. Heterocycl Chem 21, 1345 (1984)). Object of the invention The aim of the invention is to develop a simple process for the synthesis of 3-hydroxy-3 - [(2-acetamino) thien-3-yl] -aryl acid esters and nitriles. The presentation of a series of such substituted aryl acid derivatives expands the range of potential drugs. Explanation of the essence of the invention The object of the invention is a process for the synthesis of 3-hydroxy-3 - [(2-acetamino) thien-3-yl) acrylic acid esters and nitriles of the general formula I, in which V = R ² = alkyl, polymethylene R ³ = R ⁴ = alkoxycarbonyl, cyano, acetyl, phenyl mean. According to the invention the object is achieved in that 2-aminothiophene-3-carboxylic acids of the general formula III, wherein R ¹ = R ² = alkyl, polymethylene mean with acetic anhydride to 2-methylthieno [2,3-d] [1,3] oxazin-4-ones of the general formula II, wherein R ¹ = R ² = alkyl, polymethylene mean cyclized and then converted by reaction with CH-acidic compounds in structures of general formula I. The workup of the resulting products is carried out in a conventional manner.