反应详情

温度

83 °C

Add a 2; M aqueous solution of sodium carbonate (606.3; mL, 1.21; mol) to a stirring mixture of (1R,2R)-2-methyl-cyclopropanecarboxylic acid (3,4-dibromo-isothiazol-5-yl)-amide (148.1; g, 0.404; mol) and 2-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-2H-indazole (123.40; g, 0.444; mol) in HPLC grade 1,2-dimethoxyethane (1.21; L) and degas using vacuum and nitrogen. Add bis(triphenylphosphine) palladium(II) dichloride (56.77; g, 80.84; mmol) in one portion, heat at 83° C. for 10; h, cool to room temperature and filter through a pad of Celite® using ethyl acetate to give a biphasic solution. Separate the layers and extract the aqueous layer three times with dichloromethane (200; mL). Combine all the organic layers, wash with brine (200; mL) and concentrate to approximately a volume of 400; mL. Separate into two portions and purify each by silica gel chromatography by gradient 50:50; to 10:90; eluting with n-hexane:ethyl acetate to give the title compound as a light brown solid (107.32; g, 51%). MS (m/z): 391,393; (M+1).

1. additionAdd a 2
2. customdegas
3. temperatureh, cool to room temperature
4. filtrationfilter through a pad of Celite®
5. customto give a biphasic solution
6. customSeparate the layers
7. extractionextract the aqueous layer three times with dichloromethane (200; mL)
8. washCombine all the organic layers, wash with brine (200; mL)
9. concentrationconcentrate to approximately a volume of 400
10. customSeparate into two portions
11. custompurify each by silica gel chromatography by gradient 50:50
12. washeluting with n-hexane