2-[(E)-2-环丙基乙烯基]-4,4,5,5-四甲基-1,3,2-二氧硼烷

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2-amino-5-(3-bromophenyl)-5-[4-(difluoromethoxy)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one (150 g, 0.36 mmol), dimethoxyethane, 2-[(E)-2-cyclopropylvinyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (105 mg) and Na2CO3 (2 M, 2.5 mL) was degassed under argon for 5 minutes and treated with tetrakis(triphenylphosphine)palladium(0) (21 mg, 0.018 mmol). The reaction mixture was stirred for 15 hour, poured into water and extracted with ethyl acetate. The extracts were combined, dried over MgSO4 and concentrated in vacuo. Purification of the resultant residue by ICSO (EtOAc/MeOH 10/1) gave the title product as a white solid (98 mg), identified by NMR and mass spectral analyses. was degassed under argon for 5 minutes extracted with ethyl acetate dried over MgSO4 concentrated in vacuo Purification of the resultant residue by ICSO (EtOAc/MeOH 10/1)

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of tert-butyl 5-bromo-2-chlorophenylcarbamate (from the previous step) (1.0 eq.) and (E)-2-(2-cyclopropylvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (commercially available) (1.0 eq.) in toluene (0.2 M) was mixed with tetrakis(triphenyl-phosphine)palladium (5 mol %) and 2N aqueous potassium carbonate solution (2.0 eq.). The reaction was heated to 100° C. and stirred overnight. After cooling to ambient temperature, the reaction mixture was diluted with EtOAc and water. The two phases were separated, and the aqueous layer was extracted twice with EtOAc. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vacuo. The crude product was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 0-5% EtOAc/Hexanes to give (E)-tert-butyl 2-chloro-5-(2-cyclopropylvinyl)phenylcarbamate as a pale yellow solid. After cooling to ambient temperature The two phases were separated the aqueous layer was extracted twice with EtOAc The combined organic layers were washed with brine dried over anhydrous MgSO4 concentrated en vacuo The crude product was purified by flash chromatography on a COMBIFLASH® system (ISCO)

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of tert-butyl 5-bromo-2-chlorophenylcarbamate (from the previous step) (1.0 eq.) and (E)-2-(2-cyclopropylvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (commercially available) (1.0 eq.) in toluene (0.2 M) was mixed with tetrakis(triphenyl-phosphine)palladium (5 mol %) and 2N aqueous potassium carbonate solution (2.0 eq.). The reaction was heated to 100° C. and stirred overnight. After cooling to ambient temperature, the reaction mixture was diluted with EtOAc and water. The two phases were separated, and the aqueous layer was extracted twice with EtOAc. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vacuo. The crude product was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 0-5% EtOAc/Hexanes to give (E)-tert-butyl 2-chloro-5-(2-cyclopropylvinyl)phenylcarbamate as a pale yellow solid. After cooling to ambient temperature The two phases were separated the aqueous layer was extracted twice with EtOAc The combined organic layers were washed with brine dried over anhydrous MgSO4 concentrated en vacuo The crude product was purified by flash chromatography on a COMBIFLASH® system (ISCO)

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of tert-butyl 5-bromo-2-chlorophenylcarbamate (from the previous step) (1.0 eq.) and (E)-2-(2-cyclopropylvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (commercially available) (1.0 eq.) in toluene (0.2 M) was mixed with tetrakis(triphenyl-phosphine)palladium (5 mol %) and 2N aqueous potassium carbonate solution (2.0 eq.). The reaction was heated to 100° C. and stirred overnight. After cooling to ambient temperature, the reaction mixture was diluted with EtOAc and water. The two phases were separated, and the aqueous layer was extracted twice with EtOAc. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vacuo. The crude product was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 0-5% EtOAc/Hexanes to give (E)-tert-butyl 2-chloro-5-(2-cyclopropylvinyl)phenylcarbamate as a pale yellow solid. After cooling to ambient temperature The two phases were separated the aqueous layer was extracted twice with EtOAc The combined organic layers were washed with brine dried over anhydrous MgSO4 concentrated en vacuo The crude product was purified by flash chromatography on a COMBIFLASH® system (ISCO)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2-amino-5-(3-bromophenyl)-5-[4-(difluoromethoxy)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one (150 g, 0.36 mmol), dimethoxyethane, 2-[(E)-2-cyclopropylvinyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (105 mg) and Na2CO3 (2 M, 2.5 mL) was degassed under argon for 5 minutes and treated with tetrakis(triphenylphosphine)palladium(0) (21 mg, 0.018 mmol). The reaction mixture was stirred for 15 hour, poured into water and extracted with ethyl acetate. The extracts were combined, dried over MgSO4 and concentrated in vacuo. Purification of the resultant residue by ICSO (EtOAc/MeOH 10/1) gave the title product as a white solid (98 mg), identified by NMR and mass spectral analyses. was degassed under argon for 5 minutes extracted with ethyl acetate dried over MgSO4 concentrated in vacuo Purification of the resultant residue by ICSO (EtOAc/MeOH 10/1)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2-amino-5-(3-bromophenyl)-5-[4-(difluoromethoxy)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one (150 g, 0.36 mmol), dimethoxyethane, 2-[(E)-2-cyclopropylvinyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (105 mg) and Na2CO3 (2 M, 2.5 mL) was degassed under argon for 5 minutes and treated with tetrakis(triphenylphosphine)palladium(0) (21 mg, 0.018 mmol). The reaction mixture was stirred for 15 hour, poured into water and extracted with ethyl acetate. The extracts were combined, dried over MgSO4 and concentrated in vacuo. Purification of the resultant residue by ICSO (EtOAc/MeOH 10/1) gave the title product as a white solid (98 mg), identified by NMR and mass spectral analyses. was degassed under argon for 5 minutes extracted with ethyl acetate dried over MgSO4 concentrated in vacuo Purification of the resultant residue by ICSO (EtOAc/MeOH 10/1)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The title compound was prepared in an analogous manner as 6-(4-(1-(2-(dimethylamino)ethyl)-4-(4-fluoro-3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-5-(4-fluorophenyl)pyrimidin-4-amine using (E)-2-(2-cyclopropylvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane instead of 4-fluorophenyl boronic acid. LC-MS: (M+1=544, obsd.=544).

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of tert-butyl 5-bromo-2-chlorophenylcarbamate (from the previous step) (1.0 eq.) and (E)-2-(2-cyclopropylvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (commercially available) (1.0 eq.) in toluene (0.2 M) was mixed with tetrakis(triphenyl-phosphine)palladium (5 mol %) and 2N aqueous potassium carbonate solution (2.0 eq.). The reaction was heated to 100° C. and stirred overnight. After cooling to ambient temperature, the reaction mixture was diluted with EtOAc and water. The two phases were separated, and the aqueous layer was extracted twice with EtOAc. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vaccuo. The crude product was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 0-5% EtOAc/Hexanes to give (E)-tert-butyl 2-chloro-5-(2-cyclopropylvinyl)phenylcarbamate as a pale yellow solid. After cooling to ambient temperature The two phases were separated the aqueous layer was extracted twice with EtOAc The combined organic layers were washed with brine dried over anhydrous MgSO4 concentrated en vaccuo The crude product was purified by flash chromatography on a COMBIFLASH® system (ISCO)

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of tert-butyl 5-bromo-2-chlorophenylcarbamate (from the previous step) (1.0 eq.) and (E)-2-(2-cyclopropylvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (commercially available) (1.0 eq.) in toluene (0.2 M) was mixed with tetrakis(triphenyl-phosphine)palladium (5 mol %) and 2N aqueous potassium carbonate solution (2.0 eq.). The reaction was heated to 100° C. and stirred overnight. After cooling to ambient temperature, the reaction mixture was diluted with EtOAc and water. The two phases were separated, and the aqueous layer was extracted twice with EtOAc. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vaccuo. The crude product was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 0-5% EtOAc/Hexanes to give (E)-tert-butyl 2-chloro-5-(2-cyclopropylvinyl)phenylcarbamate as a pale yellow solid. After cooling to ambient temperature The two phases were separated the aqueous layer was extracted twice with EtOAc The combined organic layers were washed with brine dried over anhydrous MgSO4 concentrated en vaccuo The crude product was purified by flash chromatography on a COMBIFLASH® system (ISCO)

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of tert-butyl 5-bromo-2-chlorophenylcarbamate (from the previous step) (1.0 eq.) and (E)-2-(2-cyclopropylvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (commercially available) (1.0 eq.) in toluene (0.2 M) was mixed with tetrakis(triphenyl-phosphine)palladium (5 mol %) and 2N aqueous potassium carbonate solution (2.0 eq.). The reaction was heated to 100° C. and stirred overnight. After cooling to ambient temperature, the reaction mixture was diluted with EtOAc and water. The two phases were separated, and the aqueous layer was extracted twice with EtOAc. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vacuo. The crude product was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 0-5% EtOAc/Hexanes to give (E)-tert-butyl 2-chloro-5-(2-cyclopropylvinyl)phenylcarbamate as a pale yellow solid. After cooling to ambient temperature The two phases were separated the aqueous layer was extracted twice with EtOAc The combined organic layers were washed with brine dried over anhydrous MgSO4 concentrated en vacuo The crude product was purified by flash chromatography on a COMBIFLASH® system (ISCO)