Al technical title is built by PatSnap Al team. It summarizes the technical point description of the patent document.
A synthetic method and phthalazine technology, which are applied in the field of synthesis of 6-bromophthalazine, can solve the problems of harsh reaction conditions, low reaction yield, unsuitable amplification, etc., and achieve mild reaction conditions, high yield, and improved yield Effect
Pending Publication Date: 2020-11-13
上海毕得医药科技股份有限公司
View PDF3 Cites 0 Cited by
Summary
Abstract
Description
Claims
Application Information
AI Technical Summary
This helps you quickly interpret patents by identifying the three key elements:
Problems solved by technology
Method used
Benefits of technology
Problems solved by technology
[0011] The purpose of the present invention is to provide a synthetic method of 6-bromophthalazine, which solves the technical defects of low reaction yield, expensive raw materials, harsh reaction conditions and unsuitable scale-up in the prior art
Method used
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more
Image
Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
Click on the blue label to locate the original text in one second.
Reading with bidirectional positioning of images and text.
Smart Image
Examples
Experimental program
Comparison scheme
Effect test
Embodiment 1
[0037]
[0038] 4-Bromo-1,2-xylene (200g, 1.08mol, 1.0eq), NBS (500g, 2.81mol, 2.6eq) and AIBN (19.7g, 0.12mol, 0.11eq) were added to 2L of tetrachloride In carbon, the temperature was raised to reflux, reacted under this condition for 3 hours, cooled to room temperature, filtered, and the filtrate was spin-dried and then slurried with 400 mL of petroleum ether, filtered, and the solvent was removed under reduced pressure to obtain compound III (297 g, yield 80.1%);
Embodiment 2
[0040]
[0041] Compound III (280g, 0.82mol, 1.0eq) and tert-butyl hydrazinodicarboxylate (189.7 g, 0.82mol, 1.0eq) were dissolved in 2.8L of toluene, and a phase transfer catalyst TEAB (5.8g, 0.04 mol, 0.05eq) and 1.4L of 50% sodium hydroxide aqueous solution, then heated up to 100°C, reacted for 10 hours, after the reaction was completed, lowered to room temperature, separated, washed the organic phase with water, washed with saturated saline and dried, and then spin-dried , adding 500mL of methyl tert-butyl ether to the crude product, beating for 0.5 hours, filtering and drying to obtain compound IV (310g, yield 91.8%).
Embodiment 3
[0043]
[0044] Compound IV (300g, 0.73mol, 0.0eq) was dissolved in 1.5L of ethyl acetate, the temperature was lowered to 0°C, the temperature was controlled at 0-5°C, and 1.5L of ethyl acetate / HCl solution (4M) was added dropwise thereto , after the dropwise addition was completed, it was slowly raised to room temperature, reacted for 2 hours, and was filtered to obtain compound V (198 g, yield 95.4%).
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more
PUM
Login to view more
Abstract
The invention relates to a synthetic method of 6-bromophthalazine. The synthetic method comprises the following steps: 1) taking 4-bromo-1,2-xylene as a raw material, and adopting a free radical reaction to synthesize a compound III; 2) generating a compound IV from the compound III obtained in the step 1) and tert-butyl carbazate under the action of a sodium hydroxide water solution (50%) and a phase transfer catalyst TEAB; 3) generating a compound V from the compound IV obtained in the step 2) under the action of EA/HCl; and 4) generating a compound I from the compound V obtained in the step3) under the action of triethylamine and DDQ. The problems that in the prior art, the intermediates are unstable, and process amplification is difficult are solved. The shortages that the reaction conditions are severe, and the requirements on equipment and operators are very high, and the overall reaction yield is low are overcome. The synthesis method has the advantages of mild reaction conditions, high yield in each step, simple post-treatment, easiness in operation and suitability for process amplification.
Description
technical field [0001] The invention relates to the technical field of synthesis of organic chemical intermediates, in particular to a synthesis method of 6-bromophthalazine. Background technique [0002] 6-Bromophthalazine is a heterocyclic compound of phthalazines, which is an extremely important class of pharmaceutical intermediates with broad application prospects. The intermediate and its derivatives are used to construct many pharmaceutical active molecules. Such as the preparation of protein kinase inhibitors for the treatment of proliferative diseases, Eph receptor regulators for the treatment of nervous disorders, PI3 kinase inhibitors for the treatment of cancer, etc. [0003] At present, the synthetic route of synthetic 6-bromophthalazine mainly contains two kinds of methods: [0004] 1. Preparation with 4-bromophthalic acid as raw material [0005] [0006] This method is based on 4-bromophthalic acid as raw material, through three steps: 1) sodium borohydr...
Claims
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more
Application Information
Patent Timeline
Application Date:The date an application was filed.
Publication Date:The date a patent or application was officially published.
First Publication Date:The earliest publication date of a patent with the same application number.
Issue Date:Publication date of the patent grant document.
PCT Entry Date:The Entry date of PCT National Phase.
Estimated Expiry Date:The statutory expiry date of a patent right according to the Patent Law, and it is the longest term of protection that the patent right can achieve without the termination of the patent right due to other reasons(Term extension factor has been taken into account ).
Invalid Date:Actual expiry date is based on effective date or publication date of legal transaction data of invalid patent.
Login to view more 
Login to view more