34 results about "Formamidine hydrochloride" patented technology

The invention discloses a method for preparing 2,4-di-substituted-1,3,5-triazine. The method comprises the specific step: with substituted formamidine hydrochloride as a reaction substrate an iodine-containing compound as a catalyst, tert-butyl hydroperoxide as an oxidant, inorganic base as an acid binding agent and aliphatic ether as an organic solvent (also used as a carbon source), carrying outcarbon-hydrogen and carbon-oxygen bond deletion, nucleophilic addition, deaminizing condensation and oxidative aromatization reaction to obtain a 2,4-di-substituted-1,3,5-triazine compound, wherein achemical structural general formula of the substituted formamidine hydrochloride is shown in the description; the iodine-containing compound is selected from one of potassium iodide (KI), tetrabutylammonium iodide (TBAI), elemental iodine (I2) and N-iodosuccinimide (NIS); the inorganic base is selected from one of anhydrous potassium carbonate, anhydrous sodium carbonate, cesium carbonate, potassium hydroxide and potassium tert-butoxide; and the aliphatic ether is selected from one of methyl tert-butyl ether, ethyl ether and ethylene glycol dimethyl ether. The preparation method disclosed bythe invention has the characteristics of easily-obtained raw materials, low price and low toxicity of a catalyst, wide range of the substrate, simplicity and convenience in operation, greenness, environmental protection and the like.

The invention discloses a preparation method of riociguat. The preparation method comprises the steps of firstly, taking 1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-formamidine hydrochloride and 2-aminopropanediamide as basic raw materials, adding strong base and a solvent to perform a reflux reaction, so as to prepare 2-[1-(2-fluorobenzyl) -1H-pyrazolo[3,4-b]pyridine-3-yl]pyrimidine-4,5,6-triamine, namely a compound 3; then taking the compound 3 and dimethyl carbonate as basic raw materials, dissolving the same into methyl alcohol for reaction, so as to prepare 4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]-5-pyrimidinyl methyl carbamate, namely a compound 5, finally, dissolving the compound 5 and the strong base into the methyl alcohol, and adding methyl iodide for reacting, so as to prepare a riociguat crude product, and performing recrystallization on the riociguat crude product to obtain a riociguat refined product. The preparation method provided by the invention is relatively high in total recovery, simplified in operation and easy to industrialize.

The invention discloses a preparation method for 3-[(4-amino-5-pyrimidinyl)methyl]-5-(2-hydroxyethyl)-4-methylthiazole nitrate. The method comprises the following steps: contacting liquid sodium alkoxide with formamidine hydrochloride and then contacting an obtained substance with a compound represented by a formula (1) so as to obtain 4-amino-5-formylaminomethylpyrimidine; contacting 4-amino-5-formylaminomethylpyrimidine with an alkaline aqueous solution and then contacting an obtained substance with carbon disulfide and gamma-chloroacetyl propanol so as to obtain a compound represented by a formula (2); contacting an acidic aqueous solution with the compound represented by the formula (2) so as to obtain a compound represented by a formula (3); and contacting the compound represented by the formula (3) with hydrogen peroxide, then contacting an obtained substance with nitrate, carrying out neutralization with alkali and then carrying out solid-liquid separation so as to obtain 3-[(4-amino-5-pyrimidinyl)methyl]-5-(2-hydroxyethyl)-4-methylthiazole nitrate. With 3-[(4-amino-5-pyrimidinyl)methyl]-5-(2-hydroxyethyl)-4-methylthiazole nitrate prepared in the invention, accurate qualitative and quantitative analysis of demethylated thiamine can be realized.

A method for preparing 5-(4-bromophenyl)-4,6-dichloropyrimidine is provided. The method comprises the steps of: preparing methyl p-bromophenylacetate (Intermediate I) by catalytic esterification of p-bromophenylacetic acid, and then reacting with dimethyl carbonate to synthesize 2-(4-bromophenyl)-malonic acid-1,3-dimethyl ester (Intermediate 2), cyclizing with formamidine hydrochloride to obtain 5-(4-bromophenyl)-4,6-dihydroxypyrimidine (Intermediate 3), and then chlorinating to give the product 5-(4-bromophenyl)-4,6-dichloropyrimidine. In the process of preparing Intermediate 1 in the present invention, a solid acid is used as a catalyst. Moreover, in the process of preparing Intermediate 2, sodium methoxide is used as a base in place of sodium hydride or sodium amide used in the prior art. Furthermore, Intermediate 3 is prepared by a one-pot process.