tert-butyl N-(4-bromophenyl)carbamate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:50.01; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of tert-butyl(4-bromophenyl)carbamate (1.5 g) in tetrahydrofuran (30 mL) was added dropwise n-butyllithium (1.6 M hexane solution, 7.2 mL) at −78° C. under nitrogen atmosphere, and the mixture was stirred at the same temperature for 1 hr. Dihydro-2H-pyran-4(3H)-one (0.58 g) was added thereto, and the mixture was stirred overnight while it was allowed to be warmed. To the reaction mixture was added saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (590 mg). the mixture was stirred overnight while it to be warmed the mixture was extracted with ethyl acetate The obtained organic layer was washed with saturated brine dried over anhydrous magnesium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of tert-butyl 4-bromophenylcarbamate (1.67 g, 6.14 mmol), potassium carbonate (3.38 g, 24.46 mmol), and tetrakis(triphenylphosphine)palladium (365 mg, 0.316 mmol), was added 4,4,6-trimethyl-2-(3,3,3-trifluoroprop-1-en-2-yl)-1,3,2-dioxaborinane (1.64 g, 7.39 mmol), and degassed 1,2-dimethoxyethane (40 mL) and water (20 mL). The mixture for refluxed for 2 hours, cooled to ambient temperature, added more of 4,4,6-trimethyl-2-(3,3,3-trifluoroprop-1-en-2-yl)-1,3,2-dioxaborinane (475 mg, 2.14 mmol) and tetrakis(triphenylphosphine)palladium-(189 mg, 0.164 mmol), and refluxed for 5 hours. The reaction mixture was cooled to room temperature, filtered, diluted with water (200 mL), extracted twice with ethyl acetate (200 mL), washed with brine, dried (Na2SO4) and concentrated to an orange oil. The residue was purified by silica gel chromatography (AnaLogix® SF25-40G; 50 micron silica; eluted with 0-15% ethyl acetate in hexane at 30 mL/min) to provide the title compound (1.223 g, 4.26 mmol, 69.4% yield) as a yellow solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.53 (s, 1H), 7.52 (d, J=8.8, 2H), 7.40 (d, J=8.4, 2H), 6.03-5.99 (m, 1H), 5.97-5.94 (m, 1H), 1.48 (s, 9H); MS (DCI/NH3) m/e 305 (M+NH4)+. degassed 1,2-dimethoxyethane (40 mL) and water (20 mL) The mixture for refluxed for 2 hours refluxed for 5 hours The reaction mixture was cooled to room temperature filtered diluted with water (200 mL) extracted twice with ethyl acetate (200 mL) washed with brine dried (Na2SO4) concentrated to an orange oil The residue was purified by silica gel chromatography (AnaLogix® SF25-40G; 50 micron silica; eluted with 0-15% ethyl acetate in hexane at 30 mL/min)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Tert-butyl 4-bromophenylcarbamate (5.5 g, 20.21 mmol) was dissolved in THF, Lithium aluminum hydride (2.301 g, 60.63 mmol) was added and it was stirred at 60° C. overnight. Then it was quenched by EA, followed by H2O, concentrated and CH2Cl2 and 1M NaOH was added in, washed with CH2Cl2, extracted with CH2Cl2, dried over Na2SO4, concentrated, purified by flash chromatography (PE: EA=40:3) to give 2.1 g yellow oil. Then it was quenched by EA concentrated CH2Cl2 and 1M NaOH was added in, washed with CH2Cl2 extracted with CH2Cl2 dried over Na2SO4 concentrated purified by flash chromatography (PE: EA=40:3)

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Tert-butyl 4-bromophenylcarbamate (5.5 g, 20.21 mmol) was dissolved in THF, Lithium aluminum hydride (2.301 g, 60.63 mmol) was added and it was stirred at 60° C. overnight. Then it was quenched by EA, followed by H2O, concentrated and CH2Cl2 and 1M NaOH was added in, washed with CH2Cl2, extracted with CH2Cl2, dried over Na2SO4, concentrated, purified by flash chromatography (PE: EA=40:3) to give 2.1 g yellow oil. Then it was quenched by EA concentrated CH2Cl2 and 1M NaOH was added in, washed with CH2Cl2 extracted with CH2Cl2 dried over Na2SO4 concentrated purified by flash chromatography (PE: EA=40:3)

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of tert-butyl 4-bromophenylcarbamate (1.67 g, 6.14 mmol), potassium carbonate (3.38 g, 24.46 mmol), and tetrakis(triphenylphosphine)palladium (365 mg, 0.316 mmol), was added 4,4,6-trimethyl-2-(3,3,3-trifluoroprop-1-en-2-yl)-1,3,2-dioxaborinane (1.64 g, 7.39 mmol), and degassed 1,2-dimethoxyethane (40 mL) and water (20 mL). The mixture for refluxed for 2 hours, cooled to ambient temperature, added more of 4,4,6-trimethyl-2-(3,3,3-trifluoroprop-1-en-2-yl)-1,3,2-dioxaborinane (475 mg, 2.14 mmol) and tetrakis(triphenylphosphine)palladium-(189 mg, 0.164 mmol), and refluxed for 5 hours. The reaction mixture was cooled to room temperature, filtered, diluted with water (200 mL), extracted twice with ethyl acetate (200 mL), washed with brine, dried (Na2SO4) and concentrated to an orange oil. The residue was purified by silica gel chromatography (AnaLogix® SF25-40G; 50 micron silica; eluted with 0-15% ethyl acetate in hexane at 30 mL/min) to provide the title compound (1.223 g, 4.26 mmol, 69.4% yield) as a yellow solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.53 (s, 1H), 7.52 (d, J=8.8, 2H), 7.40 (d, J=8.4, 2H), 6.03-5.99 (m, 1H), 5.97-5.94 (m, 1H), 1.48 (s, 9H); MS (DCI/NH3) m/e 305 (M+NH4)+. degassed 1,2-dimethoxyethane (40 mL) and water (20 mL) The mixture for refluxed for 2 hours refluxed for 5 hours The reaction mixture was cooled to room temperature filtered diluted with water (200 mL) extracted twice with ethyl acetate (200 mL) washed with brine dried (Na2SO4) concentrated to an orange oil The residue was purified by silica gel chromatography (AnaLogix® SF25-40G; 50 micron silica; eluted with 0-15% ethyl acetate in hexane at 30 mL/min)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 0.263 mL (1.1 eq.) iodomethane are added dropwise at room temperature to a stirred suspension of 1.1 g (4 mmol) (4-bromo-phenyl)-carbamic acid tert-butyl ester and 2 g (1.6 eq.) cesium carbonate in 15 mL DMF. After stirring for an additional 18 hours, the reaction mixture is extracted with water/ethyl acetate and the combined organic phases are washed with brine, dried over magnesium sulfate and evaporated to yield the desired product as a colorless oil, which is used without further purification. the reaction mixture is extracted with water/ethyl acetate the combined organic phases are washed with brine dried over magnesium sulfate evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-(Pyridin-4-yl)aniline (20) was prepared in three steps: To a mixture of 4-bromoaniline (950 mg, 5.6 mmol), triethylamine (678 mg, 6.7 mmol) and DMAP (73 mg, 0.56 mmol) in DCM (30 mL) was added Boc2O (1.22g, 5.6 mmol) at 0° C. The reaction mixture was allowed to warm to room temperature and stirred for 2 hr. After the reaction was quenched with 5% NaHCO3, the mixture was extracted with DCM (3×20 mL). The organic layer was combined and dried over anhydrous MgSO4. tert-Butyl 4-bromophenylcarbamate (1.36 g, 90%) was obtained after flash column chromatography (hexane:ethyl acetate, 4:1). Suzuki coupling reaction of tert-butyl 4-bromophenylcarbamate (800 mg, 2.95 mmol) with 4-pyridineboronic acid (300 mg, 2.46 mmol) in the presence of Pd(PPh3)4 (57 mg, 0.05 mmol) and K2CO3 (678 mg, 4.9 mmol) in dioxane- H2O (4:1, 10 mL) at 90° C. for 14 hr. tert-Butyl 4-(pyridin-4-yl)phenylcarbamate (600 mg, 75%) was obtained after flash column chromatography (DCM:MeOH, 20:1). Compound 20 (380 mg, 99%) was obtained after treatment of tert-butyl 4-(pyridin-4-yl)phenylcarbamate (600 mg, 2.2 mmol) with DCM:TFA (1:1, 1 mL) for 2 hr at room temperature followed by solvent removal. To a mixture of 4-(pyridin-4-yl)aniline 20 (380 mg, 2.24 mmol) and pyridine (3 mL) in DCM (3 mL) was added phenyl chloroformate (366 mg, 2.35 mmol) at 0° C. The mixture was allowed to warm to room temperature and stirred for 3 hr. After DCM and pyridine were removed under reduced pressure, the residue was purified by flash column chromatography (DCM:MeOH, 20:1). Compound 21 (400 mg) was obtained in 65% yield.