تفاعل #2079458

معادلة التفاعل

cesium carbonate

(S)-4-(5-bromo-2,4-difluorophenyl)-4-methyl-5,6-dihydro-4H-1,3-thiazin-2-amine

pyrimidine-5-boronic acid

→

title compound

المردود 67.0%

(S)-[4-(2,4-Difluoro-5-pyrimidin-5-yl-phenyl)-4-methyl-5,6-dihydro-4H-[1,3]thiazin-2-yl]-carbamic Acid Tert-Butyl Ester

المردود 67.0%

المذيبات

water

1,2-dimethoxyethane water ethanol

ظروف التفاعل

المعالجة

1. 1
   استخلاصextracted with ethyl acetate
2. 2
   تجفيفThe organic phase is dried over magnesium sulfate
3. 3
   ترشيحfiltered
4. 4
   تركيزconcentrated under reduced pressure
5. 5
   أخرىThe residue is purified by silica gel chromatography
6. 6
   غسيلeluting with a step gradient of hexanes:ethyl acetate (7:3) to hexanes:ethyl acetate (1:1)

الإجراء التجريبي

To a 100° C. solution of (S)-4-(5-bromo-2,4-difluorophenyl)-4-methyl-5,6-dihydro-4H-1,3-thiazin-2-amine (12.6 g, 29.9 mmol, 1 equiv) in 1,2-dimethoxyethane:water:ethanol (15:7:5, 300 mL) is added a pyrimidine-5-boronic acid (25 g, 203 mmoles, 6.8 equiv) followed by cesium carbonate (58 g, 180 mmoles, 6 equiv) and bis(triphenylphosphine)palladium(II) chloride (4.2 g, 6.0 moles, 0.2 equiv). After 40 minutes, the reaction is cooled to ambient temperature, diluted with water, and extracted with ethyl acetate. The organic phase is dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue is purified by silica gel chromatography eluting with a step gradient of hexanes:ethyl acetate (7:3) to hexanes:ethyl acetate (1:1) to give the title compound (67% yield): MS (m/z): 421 (M+1).

المصدر