Method for synthesizing pyrazole [3,4-d] pyrimidine-4(5H)-ketone compounds

Abstract

The invention relates to a method for synthesizing pyrazole [3, 4-d] pyrimidine-4(5H)-ketone heterocyclic compound, which uses o-anisidine pyrazole cyanide to be reacted with ketone, to generate target compound. The reaction formula is represented as pattern, wherein R1 and R2 are substituents, as aryl, alkyl, halide, nitro, nitroso or alkoxy, while the number and positions of the substituents are not limited, R3 and R4 are alkyl, cycloalkyl or aromatic group, the catalyst is Lewis acid, protonic acid or alkali, while the best embodiments are anhydrous zinc chloride, anhydrous aluminum chloride, copper chloride, copper chloride, alcaine, sulfuric acid, pyridine, sodium carbonate, caustic soda (or caustic potash), and sodium alcoholate (potassium alcoholate), the reaction uses generate heating method, and the purification uses recrystallization or column chromatography separation. The invention has easily accessible starting materials, simple process, mild reaction condition and wide reaction application range, which can use different substrates to synthesize various pyrazole [3, 4-d] pyrimidine-4(5H)-ketone heterocyclic compounds.

Description

technical field [0001] The invention relates to a synthesis method for preparing pyrazolo[3,4-d]pyrimidin-4(5H)-one heterocyclic compounds through the reaction of o-aminocyanopyrazole and ketone. Background technique [0002] Pyrazolo[3,4-d]pyrimidin-4(5H)-ketone condensed ring compounds are a class of polynitrogen-containing heterocyclic compounds with good physiological activity, such as adenosine receptor antagonists (J.Med .Chem., 1985,28:423-427; J.Med.Chem., 1987,30:91-96; J.Med.Chem., 1991,34:2892-2898), cyclin-dependent kinase inhibitor (J.Med.Chem., 2004, 47:5894-5911; J.Med.Chem., 2005, 48:4535-4546), phosphodiesterase inhibitors (J.Med.Chem., 1997, 40: 4372-4377), antiviral drugs (J.Med.Chem., 1989, 32: 746-756; J.Med.Chem., 1985, 28: 982-987), herbicides (Organic Chemistry, 2004, 24: 1563-1568), etc., have important research value. [0003] There are few known methods for synthesizing pyrazolo[3,4-d]pyrimidin-4(5H)-one condensed ring compounds, mainly includin...

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Problems solved by technology

[0003] There are few known methods for synthesizing pyrazolo[3,4-d]pyrimidin-4(5H)-one condensed ring compounds, mainly including: (1) using o-aminopyrazole carboxylic acid or ester and formamide via The Niementowski reaction is used to synthesize pyrazolo[3,4-d]pyrimidin-4(5H)-one (J.Heterocyclic Chem., 1971,8:699-672). This method has few steps, but the reaction temperature is high, and the by-product many, difficult to control

(2) Under the catalysis, o-aminopyrazole amide and ethylsulfonate (J.Med.Chem., 1990, 33: 2174-2178) or carboxylate (J.Med.Chem., 2004, 47, 5894 -5911) reaction, this method has mild reaction conditions and high yield, but it is not applicable to the preparation of some compounds

However, in these methods, there are disadvantages that intermediates are difficult to prepare or unstable

[0004] In summary, in the existing synthetic methods of pyrazolopyrimidinones condensed ring compounds, most of them adopt o-aminoamide as reactant, and there are many preparation steps of this intermediate (Heterocycles, 1999, 50: 227 -242; J.Heterocycl.Chem.2001, 38:1045-1050), not conducive to industrial implementation

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