DD240013A1 - PROCESS FOR THE PREPARATION OF N- (1H-PYRAZOL-3-YL) -OXAMATES - Google Patents

Abstract

The invention relates to a process for the preparation of N- (1H-pyrazol-3-yl) oxamates of the general formula I in which R 1 is H, alkyl, alkenyl, aralkyl, R 2 H, alkoxycarbonyl, carbamoyl. These compounds are potential drugs with antiallergic effect. They can also serve as intermediates for the synthesis of other drugs. The aim of the invention is, starting from 3-amino-1H-pyrazoles of the general formula II in which R 1 is H, alkyl, alkenyl, aralkyl, R 2 H, alkoxycarbonyl, carbamoyl, hydroxycarbonyl, N- (1H-pyrazol-3-yl) - represent oxamates of general formula I. The synthesis of the compounds of the general formula I is carried out with reaction of the compounds of the general formula II with diethyl oxalate or oxalic acid half-ester chloride.

Description

Application of the invention

The invention relates to a process for the preparation of N- (1H-pyrazol-3-yl) -oxamates according to the general formula I in which R ^{1 is} H, alkyl, alkenyl, aralkyl,

R ² = H, alkoxycarbonyl, carbamoyl.

These compounds are potential drugs with antiallergic activity or may serve as intermediates for further pharmaco-syntheses.

Characteristic of the known technical solutions

Compounds of the general formula I have not yet been shown. Analogous N-substituted oxamates have been described several times as having antiallergic activity, i.a. a. N- (pyrid-2-yl) oxamates, N- (thien-2-yl) oxamates, N- (thiazol-2-yl) oxamates, N- (quinolin-2-yl) oxamates, and numerous N -aryl-substituted oxamates.

They are usually obtained by reacting the heterocyclic or arylamines with oxhalerihalide chloride (J.Med.Chem.22, (1979), US Pat. No. 4 054 656, US Pat. No. 4,439,445, EP 44 442, JP 80 130 961):

As intermediates, the oxamates of S-amino ^ -cyano-ö-cyanomethyl ^ -methyl- or -2-phenyl-2H-pyrazole were mentioned (J.

Amer. Chem. Soc. 81, 2456 (1959), in which, however, a 3-amino-2H-pyrazole structure is present instead of the 3-amino-1H-pyrazole structure shown in formula I.

Object of the invention

The aim of the invention is to develop a process for the synthesis of N- (1H-pyrazol-3-yl) oxamates. The presentation of a number of such substances expands the range of anti-allergic drugs.

Explanation of the essence of the invention

The essence of the invention consists in the preparation of N- {1 H-pyrazol-3-yl) oxamates of the general formula I in which R ^{1 is} H, alkyl, alkenyl, aralkyl,

R ² = H, alkoxycarbonyl, carbamoyl.

According to the invention the object is achieved in that 3-amino-pyrazoles of the general formula II, wherein R ¹ = H, alkyl, alkenyl, aralkyl,

R ² = H, alkoxycarbonyl, carbamoyl, hydroxycarbonyl, be reacted with diethyl oxalate or Oxalsäurehalbesterchlorid.

embodiments

The invention will be explained in more detail below with reference to three exemplary embodiments.

example 1 Preparation of N- (1-benzyl-4-methoxycarbonyl-1H-pyrazol-3-yl) oxamate, C ₁₆ H ₁₇ N ₃ O ₅ (331.3)

4.6 g (0.02 mol) of methyl S-amino-i-benzylMH-pyrazolecarboxylate and 27 ml (0.2 mol) of diethyl oxalate are heated to boiling for 1 hour. After cooling, the precipitate is filtered off and recrystallized from methanol.

Melting point: 142-145 ⁰ C, yield: 52%.

In an analogous way are shown:

N- (4-methoxycarbonyl-1H-pyrazol-3-yl) oxamate, C ₉ H ₁₁ N ₃ O ₅ (241.2), Melting point: 198-200 ⁰ C, yield: 40% N- (4-ethoxycarbonyl -1H-pyrazol-3-yl) -oxamate, C ₁₀ H ₁₃ N ₃ O ₅ (255.2), m.p .: 192-193.5 ° C, yield: 60% N- (1-benzyl-4-carbamoyl -1H-pyrazol-3-yl) oxamate, C ₁₅ H ₁₆ N ₄ O ₄ (316.3) mp: 126-131 ⁰ C, yield: 60%

Example 2

Preparation of N- (pyrazol-3-yl) oxamate, C ₇ H ₉ IN ₃ O ₃ (183.2) 2.54 g (0.02 mol) of 3-aminopyrazole-4-carboxylic acid (15 ml 0 , 11 mol) of diethyl oxalate are boiled in an open flask for about 20 minutes. The precipitate formed after cooling the reaction mixture is filtered off, washed with ether and recrystallized from ethanol.

Melting point: 192-195 ⁰ C, yield: 70%.

In an analogous way is shown:

N- (1-Benzyl-1H-pyrazol-3-yl) -oxamate, C ₁₄ H ₁₆ N ₃ O ₃ (273.3), m.p .: 95-97.5 ° C, Yield: 21%

Example 3

Preparation of N-Cl-crotyl-ethoxycarbonyMH-pyrazol-S-ylJ-oxamate, C ₁₄ H ₁₉ N ₃ O ₅ (309.5) 4.18 g (0.02 mol) of S-amino-i-crotyl- IH-pyrazole ^ -carboxylic acid ethyl ester in abs. Ether with 2.76 ml (0.02 mol) of triethylamine and stirred until dissolved. 2.3 ml (0.02 mol) of oxalic acid half-ester chloride are added to this solution at room temperature with stirring. After stirring for 1 hour, the precipitated triethylamine hydrochloride is filtered off and the filtrate is washed with water. The ethereal phase is dried over sodium sulfate and evaporated to dryness in vacuo. The residue obtained is recrystallized from ether-petroleum ether. Melting point: 48.5 to 51 ⁰ C, yield: 34%.

fformelblaffr ~ "

/ R ² B ¹ = H, .alkyl, alkenyl,

aralkyl.

SL, alkoxycfjbonyl,

carbamoyl

Formula I

R ¹ = H, alkyl, alkenyl,

aralkyl

2 R ss H, alkoxycarbonyl,

carbamoyl, carbamoyl! Formula II

Claims (1)

Claim: A process for the preparation of N- (1H-pyrazol-3-yl) oxamates of general formula I in which R ^{1 is} H, alkyl, alkenyl, aralkyl, R ^{2 is} H, alkoxycarbonyl, carbamoyl, characterized in that 3-amino-1H-pyrazoles of the general formula II in which R 'is H, alkyl, alkenyl, aralkyl, R ² = H, alkoxycarbonyl, carbamoyl, hydroxycarbonyl, be reacted with diethyl oxalate or Oxalsäurehalbesterchlorid, whereby the compounds of general formula I are formed with elimination of 'ethanol or hydrogen chloride.