反应详情

温度

120 °C

In two separate Smith process vials (10-20 mL capacity) are added 3-iodo-1H-thieno[3,2-c]pyrazole-5-carboxylic acid methyl ester [420 mg, 1.36 mmol, Intermediate (26)], 5-(tert-butyl-dimethyl-silanyloxymethyl)-1H-indole-2-boronic acid 1-carboxylic acid tert-butyl ester [912 mg, 2.25 mmol, Intermediate (8), prepared as described in Example 1-4 of International Patent Application Publication No. WO 02/32861], potassium carbonate (2M, aqueous, 2.25 mL) tetrakis(triphenylphosphine)palladium(0) (87 mg, 0.0752 mmol), and a mixture of toluene/ethanol (9:3 mL). The reaction tube is filled with N2 and sealed using capping device. The reaction mixture is heated to 120° C. using microwave (Personal chemistry optimizer) for 900 seconds. After reactions are over combined them into a flask, diluted with ethyl acetate (50 mL) and washed twice with water (10 mL), brine and dried over sodium sulfate. Purification by chromatography on 35 g silica gel cartridge (30-50% ethyl acetate gradient in heptane) gave two major fractions. The higher rising Rf fractions are combined and evaporated solvent in vacuo to give 5-(tert-butyl-dimethyl-silanyloxymethyl)-2-(5-methoxycarbonyl-1H-thieno[3,2-c]pyrazol-3-yl)-indole-1-carboxylic acid tert-butyl ester [653 mg, Intermediate (27)] as light yellow solid. LC/MS: 542 (M+H). The lower rising Rf fractions are combined and evaporated in vacuo to give product 3-[5-(tert-butyl-dimethyl-silanyloxymethyl)-1H-indol-2-yl]-1H-thieno[3,2-c]pyrazole-5-carboxylic acid methyl ester [253 mg, Intermediate (28)] as light yellow solid; LC/MS: 442 (M+H).

1. customIn two separate Smith process vials (10-20 mL capacity)
2. customsealed
3. customfor 900 seconds
4. washwashed twice with water (10 mL), brine
5. dry with materialdried over sodium sulfate
6. customPurification by chromatography on 35 g silica gel cartridge (30-50% ethyl acetate gradient in heptane)
7. customgave two major fractions
8. customevaporated solvent in vacuo