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2,4-dichloro-6,7-dimethoxyquinazoline solvate and preparation method thereof

A technology of dimethoxyquinazoline and solvate, applied in the field of chemical synthesis, can solve problems such as chemically unstable synthesis problems, and achieve the effects of low cost, simple process and high yield

Inactive Publication Date: 2020-05-12
CHONGQING WORLD HAORUI PHARM CHEM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There are certain limitations in the above-mentioned synthetic method and its products, and the disadvantage is that (formula Ⅰ-1) itself is easily hydrolyzed. When the ice water quenching time is long, the water temperature exceeds 10~15 ℃, and the drying of the filter cake obtained by filtering And during storage, a part in (formula I-1) will be hydrolyzed into raw material intermediate (formula VIII), 2,4-dichloro-6,7-dimethoxyquinazoline (formula I-1) Chemical instability poses a problem for the synthesis of oxazinoids

Method used

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  • 2,4-dichloro-6,7-dimethoxyquinazoline solvate and preparation method thereof
  • 2,4-dichloro-6,7-dimethoxyquinazoline solvate and preparation method thereof
  • 2,4-dichloro-6,7-dimethoxyquinazoline solvate and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0031] Preparation of 2,4-dichloro-6,7-dimethoxyquinazoline n-propanol solvate:

[0032] Add 66.6g (0.3mol) of 6,7-dimethoxy-2,4-(1H,3H)-quinazolinedione (Formula VIII) and 380g of phosphorus oxychloride in a dry and clean 1000mL three-neck flask (2.5mol) and DMF3mL, heated to reflux at 105°C, reacted for 4h, controlled the temperature of the reaction solution below 80°C by vacuum distillation, and evaporated excess phosphorus oxychloride; cooled the residue of vacuum distillation to 15°C, and distilled the residue Pour into 500g of crushed ice for quenching; when extracting, use 300mL of dichloromethane x 2 times, wash the extract with tap water once, then wash with saturated brine once, dry with 50g of anhydrous sodium sulfate; remove by suction Sodium sulfate, dichloromethane was distilled off under reduced pressure to obtain 81g of 2,4-dichloro-6,7-dimethoxyquinazoline concentrate; first add 80mL of n-propanol to the obtained concentrate, and stir at 20°C 30min, then add ...

Embodiment 2

[0034] Preparation of 2,4-dichloro-6,7-dimethoxyquinazoline n-propanol solvate:

[0035] Add 66.6g (0.3mol) of 6,7-dimethoxy-2,4-(1H,3H)-quinazolinedione (Formula VIII) and 380g of phosphorus oxychloride in a dry and clean 1000mL three-neck flask (2.5mol) and DMF3mL, heated to reflux at 105°C, reacted for 4h, controlled the temperature of the reaction solution below 80°C by vacuum distillation, and evaporated excess phosphorus oxychloride; cooled the residue of vacuum distillation to 15°C, and distilled the residue Pour into 500g of crushed ice for quenching; when extracting, use 300mL of dichloromethane x 2 times, wash the extract with tap water once, then wash with saturated brine once, dry with 50g of anhydrous sodium sulfate; remove by suction Sodium sulfate, dichloromethane was distilled off under reduced pressure to obtain 79.5 g of 2,4-dichloro-6,7-dimethoxyquinazoline concentrate; first add 60 mL of n-propanol to the obtained concentrate, and Stirring at low temperatu...

Embodiment 3

[0037] Preparation of 2,4-dichloro-6,7-dimethoxyquinazoline n-propanol solvate:

[0038]Add 66.6g (0.3mol) of 6,7-dimethoxy-2,4-(1H,3H)-quinazolinedione (Formula VIII) and 380g of phosphorus oxychloride in a dry and clean 1000mL three-neck flask (2.5mol) and DMF3mL, heated to reflux at 105°C, reacted for 4h, controlled the temperature of the reaction solution below 80°C by vacuum distillation, and evaporated excess phosphorus oxychloride; cooled the residue of vacuum distillation to 15°C, and distilled the residue Pour into 500g of crushed ice for quenching; when extracting, use 300mL of dichloromethane x 2 times, wash the extract with tap water once, then wash with saturated brine once, dry with 50g of anhydrous sodium sulfate; remove by suction Sodium sulfate, dichloromethane was distilled off under reduced pressure to obtain 80.7g of 2,4-dichloro-6,7-dimethoxyquinazoline concentrate; Stir for 45min, then add 95mL of chloroform, and stir to precipitate crystals. After filt...

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Abstract

The invention provides a 2,4-dichloro-6,7-dimethoxyquinazoline solvate. The 2,4-dichloro-6,7-dimethoxyquinazoline solvate has a chemical structure as shown in a formula I which is described in the specification. The preparation method comprises the following specific steps: adding a first solvent, namely n-propanol into a 2,4-dichloro-6,7-dimethoxyquinazoline concentrate, and carrying out stirringat a temperature of minus 5 DEG C to 60 DEG C; and adding a second solvent, carrying out stirring for crystallization, and carrying out filtering and drying so as to obtain faint yellow crystalline solid powder, namely the 2,4-dichloro-6,7-dimethoxyquinazoline solvate. The 2,4-dichloro-6,7-dimethoxyquinazoline n-propanol solvate synthesized by using the method provided by the invention is not easy to be hydrolyzed into an intermediate in the drying and storage processes, and the problem of trouble to synthesis of azolizine drugs due to chemical instability of conventional 2,4-dichloro-6,7-dimethoxyquinazoline is solved.

Description

technical field [0001] The invention belongs to the technical field of chemical synthesis, in particular to a 2,4-dichloro-6,7-dimethoxyquinazoline solvate and a preparation method thereof Background technique [0002] Azosin-type α-receptor blockers are a common class of antihypertensive drugs, which selectively block α1 receptors on the post-synaptic membrane of vascular smooth muscle, and then dilate blood vessels to produce an antihypertensive effect. This type of drug can be used for hypertension complicated with benign prostatic hyperplasia, hypertension complicated with abnormal glucose and lipid metabolism, refractory hypertension, hypertensive emergencies, etc. The commonly used oxazin class α-receptor blockers in clinic include Prazosin Hydrochloride (Formula A), Terazosin Hydrochloride (Formula B), Doxazosin Mesylate (Doxazosin mesylate) ( Formula C), Bunazosin hydrochloride (Bunazosinhydrochloride) (Formula D), Alfuzosin Hydrochloride (Alfuzosinhydrochloride) (F...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D239/96
CPCC07B2200/13C07D239/96
Inventor 邵劲松封杰任彦荣林国跃
Owner CHONGQING WORLD HAORUI PHARM CHEM