Background and overview[1]
4-Bromoquinoline-6-carboxylic acid can be used as a pharmaceutical synthesis intermediate. Such as preparing scutellarin intermediate scutellarin aglycone. Erigerm breviscapus (Vant.) Hand-Mass, commonly known as Erigerm breviscapus, is the dried whole plant of the Asteraceae plant Erigermbreviscapus (Vant.) Hand-Mass. It was first seen in “Southern Yunnan Materia Medica” written by Lan Zhi’an, a medical scientist in the Ming Dynasty. Bitter, warm in nature, it can cure rheumatic pain.” “Yunnan Chinese Herbal Medicine” clearly states that Erigeron is mainly used to dispel cold, relieve external symptoms, activate blood circulation and relax muscles, colds, headaches, nasal congestion, bruises, etc. Breviscapine is the general name for the flavonoid active ingredients extracted from breviscapus. The scutellarin drugs currently used clinically use scutellarin as the main active ingredient. Its main pharmacological ingredient is scutellarin (1-1, also known as scutellarin, molecular formula: C21H18O12, molecular weight: 462.37, CAS:27740-01-8). According to the quality standards for scutellarin recorded in the 2015 edition of the Chinese Pharmacopoeia, scutellarin raw materials for injection contain no less than 98.0% scutellarin, and scutellarin raw materials for oral use contain no less than 90.0% scutellarin. %. Modern pharmacological research shows that scutellarin has the effects of increasing cerebral blood flow, reducing vascular resistance, anti-platelet and red blood cell aggregation, and reducing blood viscosity.
Preparation[1]
The preparation of 2,6-dimethoxyhydroquinone is as follows:
Step 1): In a 500mL Erlenmeyer flask, dissolve K3Fe(CN)6 (2.0g, 7.0mmol) in water (10.0g), add acetone (100g) and 1,3,5-trimethyl to it Oxybenzene (2-3) (16.4g, 100mmol), stir evenly at 25°C, add H2O2 (30%, 34g, 300mmol) to it, stir for 20h at 25°C, yellow-green solid precipitates, add to the above reaction system water (200 mL), and suction filtration to obtain 13.8 g of yellow solid 2,6-dimethoxybenzoquinone, yield 82%, m.p. 252-255°C.
Step 2): In a 250mL single-mouth bottle, add water (100mL) and 2,6-dimethoxybenzoquinone (2-4, prepared in Example 1) (13.3g, 80mmol) in sequence, and then add Add sodium dithionite Na2S2O4 (20.1g, 120mmol), heat the system to reflux for 1 hour (the system changes from turbid to clear), cool, a large amount of white solid precipitates, filter, and vacuum dry to obtain the product 2,6-dimethoxyhydroquinone. 11.7g, yield 86%, m.p. 160-162°C.
Application
4-Bromoquinoline-6-carboxylic acid can be used as a pharmaceutical synthesis intermediate. For example, to prepare scutellarin intermediate and scutellarin aglycone synthesis intermediate, add 2,6-dimethoxy-4-hydroxyphenol (11.3g, 66.5mmol), dichloromethane ( 80mL), acetic anhydride (54g), BF3·Et2O (33g, 232mmol), stir and heat to reflux for 3 hours. At this time, a large amount of yellow solid precipitates. Cool and filter to obtain 17.5g of yellow solid, yield 87%, m.p.207- 209℃.
Main reference materials
[1] CN201610897971.X An intermediate of scutellarin and its preparation method and application
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