Application background and overview of 2-dimethylaminopyrimidine-5-boronic acid
2-Chloro-5-fluorobenzyl alcohol can be used as a pharmaceutical synthesis intermediate. If you inhale 2-chloro-5-fluorobenzyl alcohol, please move the patient to fresh air; if there is skin contact, take off contaminated clothing, wash the skin thoroughly with soap and water, and seek medical treatment if you feel uncomfortable; if In case of eye contact, separate eyelids, rinse with running water or normal saline, and seek medical attention immediately; if ingested, rinse your mouth with hydroxypyridine immediately, do not induce vomiting, and seek medical attention immediately.
Application structure of 2-dimethylaminopyrimidine-5-boronic acid
Applications of 2-dimethylaminopyrimidine-5-boronic acid
2-Chloro-5-fluorobenzyl alcohol can be used as a pharmaceutical synthesis intermediate. For example, the following compounds are synthesized:
The specific steps are:
Step 1: Under nitrogen protection, add 9-bromo-6-tert-butyl-10-methoxy-2-oxo-6,7-dihydro-2H-pyrido[2,1-a] To a solution of isoquinoline-3-carboxylic acid ethyl ester (100 mg, 0.23 mmol) in 1,4-dioxane (2 mL) and water (0.5 mL) was added 2-methylaminopyrimidine-5-boronic acid (39 mg, 0.25 mmol), potassium carbonate (77.1 mg, 0.558 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]palladium dichloride (14 mg, 0.019 mmol).
The mixture was heated to 85°C and stirred at 85°C for 20 hours. The mixture was diluted with ethyl acetate (20 mL), then washed with water (30 mL) and saturated brine (20 mL), then dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product, which was purified by preparatory plate chromatography to obtain Off-white solid 6-tert-butyl-10-methoxy-9-[2-(methylamino)pyrimidin-5-yl]-2-oxo-6,7-dihydro-2H-pyrido[2 ,1-a]isoquinoline-3-carboxylic acid methyl ester.
Step 2: To 6-tert-butyl-9-[2-(dimethylamino)pyrimidin-5-yl]-10-methoxy-2-oxo-6,7-dihydro-2H -To a solution of pyrido[2,1-a]isoquinoline-3-carboxylic acid methyl ester (18 mg, lithium carbonate 0.04 mmol) in ethanol (2 mL), 10% sodium hydroxide solution (0.4 mL) was added, and the mixture was brought to room temperature Stir for 4h. The mixture was concentrated to give crude product.
Dissolve the crude product in water (20 mL) and wash with ethyl acetate (20 mL × 5). The aqueous phase was then adjusted to pH 2 with 1 M hydrochloric acid solution, and then extracted with ethyl acetate (10 mL × 5). The organic phases were combined and washed with water (20 mL × 5), and then concentrated to obtain a white solid 6-tert-butyl-9-[2-(dimethylamino)pyrimidin-5-yl]-10-methoxy-2-oxo Generation-6,7-dihydro-2H-pyrido[2,1-a]isoquinoline-3-carboxylic acid.
