Preparation method of oxlagrel intermediate
A technology of oxaraguridine and intermediates, which is applied in the field of organic chemical synthesis, can solve problems such as cumbersome synthetic routes, and achieve the effects of cheap and easy-to-obtain raw materials, simple post-processing methods, and low equipment requirements
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
preparation example Construction
[0035] The present invention relates to a preparation method of an elageril intermediate, the specific elageril intermediate is compound 1, and its chemical name is: 5-bromo-1-(2-fluoro-6-trifluoromethylbenzyl)- 6-methylpyrimidine(1H,3H)-2,4-dione[5-bromo-1-(2-fluoro-6-(trifluoromethyl)benzyl)-6-methylpyrimidine-2,4(1H,3H)- dione]; The preparation method of compound 1 of the present invention has following two steps:
[0036]
[0037](1) With compound 7 (2-fluoro-6-(trifluoromethyl) benzyl bromide) as the starting material, it is dissolved in an aprotic polar solvent, then alkali metal carbonate and urea are added, stirred The heating reaction is carried out under the following conditions, and after the reaction is completed, the first post-treatment is carried out to obtain the crude product of compound 4, and the pure product of compound 4 is obtained after recrystallization;
[0038] (2) Dissolve compound 4 prepared in step (1) in an aprotic polar solvent, then add comp...
Embodiment 1
[0048] The preparation of compound 4, the specific process is as follows:
[0049]
[0050] Add 51.2 g (200 mmol) of compound 7 (2-fluoro-6-(trifluoromethyl)benzyl bromide, a commercial reagent, CAS No. 239087-08, into a 1000 ml single-necked flask with a magnetic stir bar -2), add 500 mL of acetonitrile solvent, then add 41.4 g (300 mmol) of potassium carbonate, and 24 g (400 mmol) of urea, heat the reaction system to 50 ° C for heating and stirring reaction, heating and stirring for 12 hours Finally, after removing the filter residue by suction filtration, the obtained filtrate was concentrated under reduced pressure to remove the acetonitrile solvent to obtain the crude product of compound 4. In order to reduce the adsorption of the product on the filter residue and improve the product yield, the filter residue was washed twice with dichloromethane ; The crude product was recrystallized with a mixed solvent of ethanol-water (volume ratio 1:1) to obtain 43.4 g of a white ...
Embodiment 2
[0056] The preparation of the target product compound 1, the specific process is as follows:
[0057]
[0058] Under nitrogen atmosphere, 23.6 g (100 mmol) of compound 4 and 22.9 g (110 mmol) of ethyl 2-bromoacetoacetate compound 9 (commercial reagent , CAS number is 609-13-2; also can refer to the preparation method of literature: European Journal of Organic Chemistry, 2017, 31, 4543-4547; Journal of Medicinal Chemistry, 2016, 59 (17), 7840-7855, by acetyl Ethyl acetate and NBS one-step reaction high yield preparation), then add 100 milliliters of anhydrous DMAc (dimethylacetamide) to dissolve, the reaction system is reduced to 0 degrees;
[0059] Slowly add 13.8 ml (105 mmol) of trimethylsilyl bromide (TMSBr) dropwise under stirring with a constant pressure dropping funnel. After the dropwise addition is complete, the temperature of the reaction system is raised to 80° C., and the reaction is stirred for 16 hours until the end of the reaction;
[0060] After the reaction...
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More