(2,3,4-trifluorophenyl)boronic acid

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-bromo-1-(propan-2-yl)-1H-indole-3-carboxaldehyde (100 mg, 0.376 mmol) and 2,3,4-trifluorophenylboronic acid (79 mg, 0.451 mmol) in dioxane (2 mL) and water (0.5 mL) in a 5 mL microwave reaction vial was added potassium carbonate (156 mg, 1.13 mmol) and dichloro[1,1′-bis(di-t-butylphosphino)ferrocene]palladium (II) (25 mg, 0.038 mmol). The reaction was placed under nitrogen, sealed and heated in a microwave reactor at 140° C. for 15 minutes. The solvent was removed in vacuo and the residue was partitioned with ethyl acetate and aqueous sodium bicarbonate and extracted twice with ethyl acetate. The organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated. The residue was purified on silica gel (COMBI FLASH 24 gm column, gradient of 0-100% ethyl acetate/hexanes) to give the title intermediate (82 mg). sealed The solvent was removed in vacuo the residue was partitioned with ethyl acetate and aqueous sodium bicarbonate extracted twice with ethyl acetate The organic layers were washed with brine dried over sodium sulfate filtered concentrated The residue was purified on silica gel (COMBI FLASH 24 gm column, gradient of 0-100% ethyl acetate/hexanes)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium carbonate (0.188 mL, 2M, 0.376 mmol) was added to a stirred room temperature solution of 5-bromo-1-(propan-2-yl)-1H-indole-3-carbaldehyde (50 mg, 0.188 mmol), 2,3,4-trifluorophenylboronic acid (66 mg, 0.376 mmol) and PdCl2(dppf) (13.7 mg, 0.019 mmol) in DMF (1.0 mL) and the reaction mixture was stirred at 80° C. for 12 hours. The reaction mixture was cooled to room temperature, partitioned between ethyl acetate (2×15 mL) and water (10 mL), washed with saturated sodium bicarbonate (10 mL), brine (10 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure to give the title compound (50 mg). The reaction mixture was cooled to room temperature partitioned between ethyl acetate (2×15 mL) and water (10 mL) washed with saturated sodium bicarbonate (10 mL), brine (10 mL) dried over sodium sulfate filtered concentrated under reduced pressure

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 4-{8-[(4-methyl-5-trifluoromethyl-2-bromophenyl)methyl]-2-oxo-1-oxa-3,8-diazaspiro[4.5]dec-3-yl}benzoate (30 mg, 0.055 mmol) in dioxane (1.5 mL) and water (0.5 mL) in a 5 mL microwave reaction vial were added 2,3,4-trifluorophenylboronic acid (20 mg, 0.111 mmol), 1,1′-bis(diphenylphosphino)ferrocene palladium (II) dichloride dichloromethane complex (9 mg, 0.011 mmol) and lithium hydroxide mono-hydrate (5 mg, 0.111 mmol). The reaction was heated in a microwave at 120° C. for 15-30 minutes. The crude reaction was diluted with acetonitrile and water, filtered and purified by reverse phase chromatography using a gradient of acetonitrile and water with 0.1% ammonium hydroxide. Lypholization of the desired fractions afforded the title compound (13.4 mg) as a white solid. The crude reaction filtered purified by reverse phase chromatography

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a degassed solution of 2-bromo-5-ethoxy-4-methylbenzaldehyde (300 mg, 1.31 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (53.8 mg, 0.131 mmol; S-Phos ligand) palladium (II) acetate (14.7 mg, 0.065 mmol) in THF (8 mL) were added K3PO4 (834 mg, 3.93 mmol) and (2,3,4-trifluorophenyl)boronic acid (276, 1.57 mmol). The reaction mixture was stirred at 70° C. under a N2 atmosphere for 16 hours, cooled to room temperature and filtered and the filtrate was concentrated by evaporation under reduced pressure. The residue was purified on a silica gel column eluting with 5 to 10% EtOAc in hexanes to provide the title intermediate (255 mg) as white solid. cooled to room temperature filtered the filtrate was concentrated by evaporation under reduced pressure The residue was purified on a silica gel column eluting with 5 to 10% EtOAc in hexanes

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a degassed solution of 2-bromo-5-ethoxybenzaldehye (300 mg, 1.31 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (53.8 mg, 0.131 mmol; S-Phos ligand), palladium (II) acetate (14.7 mg, 0.065 mmol) in THF (8 mL) were added K3PO4 (834 mg, 3.93 mmol) and (2,3,4-trifluorophenyl)boronic acid (276, 1.57 mmol). Reaction mixture was stirred at 70° C. under a N2 atmosphere for 16 hours, cooled to room temperature and then filtered. The filtrate was concentrated by evaporation under reduced pressure. The residue was purified on a silica gel column eluting with 5 to 10% EtOAc in hexanes to provide the title intermediate (255 mg) as white solid. Reaction mixture cooled to room temperature filtered The filtrate was concentrated by evaporation under reduced pressure The residue was purified on a silica gel column eluting with 5 to 10% EtOAc in hexanes

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Potassium carbonate (0.418 mL, 0.836 mmol), Pd(OAc)2 (2.82 mg, 0.013 mmol) was added to a stirred, room temperature mixture of 4-bromo-1-methyl-1H-pyrazole-3-carbaldehyde (79 mg, 0.418 mmol) and (2,3,4-trifluorophenyl)boronic acid (96 mg, 0.543 mmol) in EtOH (0.7 mL) and the mixture was stirred at 90° C. for 24 hours. The mixture was cooled, aqueous sodium hydrogen carbonate (saturated, 10 mL) was added and the mixture was extracted with ethyl acetate (2×15 mL). The combined organic fractions were washed with water, dried (MgSO4) and filtered. The solvent was evaporated under reduced pressure to give the crude intermediate which was used in the next step. The mixture was cooled the mixture was extracted with ethyl acetate (2×15 mL) The combined organic fractions were washed with water dried (MgSO4) filtered The solvent was evaporated under reduced pressure

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

Procedure: The title compound, white solid (18 mg, 20%), MS (ISP) m/z=356.5 [(M+H)+], mp 187° C., was prepared in accordance with the general method of example 1 from 7-bromo-1-oxo-2,3,4,5-tetrahydro-[1,4]diazepino[1,2-a]indole-9-carbonitrile (intermediate 20) (76.0 mg, 0.25 mmol) and commercially available 2,3,4-trifluoro-phenylboronic acid (57.2 mg, 0.325 mmol).

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

Procedure: The title compound, white solid (17 mg, 19%), MS (ISP) m/z=356.5 [(M+H)+], mp 238° C., was prepared in accordance with the general method of example 1 from 6-bromo-10-methyl-1-oxo-1,2,3,4-tetrahydro-pyrazino[1,2-a]indole-8-carbonitrile (intermediate 16) (76 mg, 0.25 mmol) and commercially available 2,3,4-trifluoro-phenylboronic acid (57.2 mg, 0.325 mmol).

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

Procedure: The title compound, white solid (13 mg, 15%), MS (ISP) m/z=342.4 [(M+H)+], mp 294° C., was prepared in accordance with the general method of example 1 from 6-bromo-1-oxo-1,2,3,4-tetrahydro-pyrazino[1,2-a]indole-8-carbonitrile (intermediate 15) (72.5 mg, 0.25 mmol) and commercially available 2,3,4-trifluoro-phenylboronic acid (57.2 mg, 0.325 mmol).

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

Procedure: The title compound, white solid (32 mg, 18%), MS (ISP) m/z=365.5 [(M+H)+], mp 205.5° C., was prepared in accordance with the general method of example 1 from 6-bromo-8-chloro-10-methyl-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one (intermediate 12) (157 mg, 0.5 mmol) and commercially available 2,3,4-trifluorophenylboronic acid (114 mg, 0.65 mmol).

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

Procedure: The title compound, white solid (32 mg, 18%), MS (ISP) m/z=365.5 [(M+H)+], mp 205.5° C., was prepared in accordance with the general method of example 1 from 6-bromo-8-chloro-10-methyl-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one (intermediate 12) (157 mg, 0.5 mmol) and commercially available 2,3,4-trifluorophenylboronic acid (114 mg, 0.65 mmol).

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

Procedure: The title compound, white solid (21 mg, 24%), MS (ISP) m/z=349.5 [(M+H)+], mp 130° C., was prepared in accordance with the general method of example 1 from 6-bromo-8-fluoro-10-methyl-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one (intermediate 14) (74.3 mg, 0.25 mmol) and commercially available 2,3,4-trifluorophenylboronic acid (57.2 mg, 0.325 mmol).