Synthetic method of pharmaceutical intermediate pyrano [2, 3-d] [1, 3] thiazolo [3, 2-a] pyrimidine derivative

A technology of pyrimidine derivatives and synthesis methods, which is applied in the field of derivative synthesis, can solve the problems of increasing production costs, waste liquid, difficult recovery and reuse of reaction solvents, and continuous production of synthesis processes, achieving broad market potential and application prospects , the effect of good industrialized large-scale use value

Pending Publication Date: 2022-05-13
南京欣久医药科技有限公司
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Problems solved by technology

[0004] But above-mentioned synthesis method also has the following problems: 1, the used organic base catalyst can not be recycled, also produces a large amount of waste liquids while increasing production cost, causes the rise of environmental pollution and treatment difficulty; 2, is lost in the environment The removed organic base catalyst is not easy to be degraded by microorganisms; 3, the selectivity of the catalyst is not high, so that a large amount of by-products are left in the reaction solvent, causing the reaction solvent to be difficult to recycle and reuse; 4, because the catalyst and the reaction solvent cannot be recycled, The whole synthesis process cannot be produced continuously, but can only be produced intermittently

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  • Synthetic method of pharmaceutical intermediate pyrano [2, 3-d] [1, 3] thiazolo [3, 2-a] pyrimidine derivative
  • Synthetic method of pharmaceutical intermediate pyrano [2, 3-d] [1, 3] thiazolo [3, 2-a] pyrimidine derivative
  • Synthetic method of pharmaceutical intermediate pyrano [2, 3-d] [1, 3] thiazolo [3, 2-a] pyrimidine derivative

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preparation example Construction

[0034] As a technical optimization scheme of the present invention, the synthesis method comprises the following steps:

[0035] Step 1: Add the pre-prepared mixed solvent into the one-necked bottle, and then add aldehyde, malononitrile, 7-hydroxy-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidine - 5-ketone and alkaline ionic liquid catalyst, magnetic stirring at room temperature to form a reaction solution;

[0036] Step 2: uniformly heat the above-mentioned reaction solution in a water bath to 35-50°C, and magnetically stir the reaction at this temperature for 4-8 minutes, then immediately stop stirring and heating, and the reaction is completed;

[0037] Step 3: Cool the mixture obtained after the reaction to room temperature naturally to obtain a large amount of solids, which are left to stand and filtered with suction, and the filter residue is washed with absolute ethanol and vacuum-dried to obtain the target product pyrano[2,3-d][ 1, 3] Thiazolo [3, 2-a] pyrimidine derivat...

Embodiment 1

[0049]

[0050] In this example, 8-amino-6-phenyl-5-oxo-2,3-dihydro-5H,6H-pyrano[2,3-d][1,3]thiazolo[3, 2-a] the steps of pyrimidine-7-carbonitrile (IV) are as follows:

[0051] (1) At room temperature, add 1.0 mmol benzaldehyde ( I), 1.0 mmol malononitrile (II) and 1.0 mmol 7-hydroxy-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one (III), Stir magnetically until evenly mixed, and then add 0.05 mmol of basic ionic liquid catalyst.

[0052] (2) The three-necked flask was heated in a water bath, and the temperature was evenly raised to 39°C, and the reaction was stirred at this temperature for 6 minutes.

[0053] (3) After the reaction, the reaction solution was naturally cooled to room temperature, and a large amount of solids were precipitated, left to age for 2 hours, filtered under reduced pressure, and separated to obtain the filtrate and filter residue: the filter residue was crushed and washed with absolute ethanol (5mL×3) , 0.30 g of white solid was obtained afte...

Embodiment 2

[0057]

[0058] In this example, 8-amino-6-(4-chlorophenyl)-5-oxo-2,3-dihydro-5H,6H-pyrano[2,3-d][1,3] was synthesized The steps of thiazolo[3,2-a]pyrimidine-7-carbonitrile (IV) are as follows:

[0059] (1) At room temperature, add 1.0mmol p-chlorobenzene to a 50mL three-necked flask with a spherical condenser, a thermometer and a magnetic stirrer containing 8mL of a mixed solvent (the volume ratio of ethanol and [Bmim]Br is 8:1.0) Formaldehyde (I), 1.0mmol malononitrile (II) and 1.0mmol 7-hydroxy-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one (III ), magnetically stirred until uniformly mixed, and then added 0.05mmol alkaline ionic liquid catalyst.

[0060] (2) The three-necked flask was heated in a water bath, and the temperature was uniformly raised to 37°C, and the reaction was stirred at this temperature for 5 minutes.

[0061] (3) After the reaction, the reaction solution was naturally cooled to room temperature, and a large amount of solids were precipitated, l...

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Abstract

The invention relates to the field of pharmaceutical chemical industry, and particularly discloses a synthetic method of a pharmaceutical intermediate pyrano [2, 3-d] [1, 3] thiazolo [3, 2-a] pyrimidine derivative, which comprises the following steps: in a catalytic system consisting of a basic ionic liquid catalyst and a mixed solvent, taking aldehyde, malononitrile and 7-hydroxy-2, 3-dihydro-5H-[1, 3] thiazolo [3, 2-a] pyrimidine-5-ketone as raw materials, and reacting at the temperature of 60-80 DEG C to obtain the pyrano [2, 3-d] [1, 3] thiazolo [3, 2-a] pyrimidine derivative. And reacting at the temperature of between 35 and 50 DEG C for 4 to 8 minutes, and preparing to obtain the pyrano [2, 3-d] [1, 3] thiazolo [3, 2-a] pyrimidine derivative medical intermediate. According to the synthesis method, through selection of a plurality of elements such as catalyst, reaction solvent and catalytic system regeneration, the target product can be obtained at high yield, and the synthesis method has good industrial large-scale use value in the technical field of medical intermediate synthesis.

Description

technical field [0001] The invention relates to a synthesis method of derivatives, in particular to a synthesis method of a pharmaceutical intermediate pyrano[2,3-d][1,3]thiazolo[3,2-a]pyrimidine derivatives, belonging to the field of medicine and chemical industry . Background technique [0002] Pyrimidine derivatives are a very important class of active substances in the fields of pesticides and biomedicine, and have broad-spectrum biological activities, such as insecticidal, bactericidal, herbicidal, antiviral, and anticancer. The thiazolopyrimidine compound containing two important active unit structures of thiazole and pyrimidine is an important analogue of purine, which has biological activities such as anti-virus and anti-tumor, and has a wide range of uses in the field of medicine. Thiazolo[3,2-a]pyrimidine derivatives, as the most studied class of nitrogen and sulfur heterocyclic compounds with various important biological activities among thiazolopyrimidine compou...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D513/14
CPCC07D513/14
Inventor 沈智培卢蓉蓉陈智豪
Owner 南京欣久医药科技有限公司
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