(2-methoxycarbonylphenyl)boronic acid

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

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

Conditions: temp:0.00; 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 microwave vessel was added 2-(methoxycarbonyl)phenylboronic acid (63.4 mg, 0.352 mmol), 2-bromo-4-fluoro-1-nitrobenzene (77 mg, 0.35 mmol), diacetoxypalladium (0.93 mg, 4.1 mmol) and dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (3.47 mg, 8.45 μmol). Ethanol (1760 μl) and sodium carbonate (176 μl, 0.352 mmol) were added and the mixture was reacted in a microwave reactor at 100° C. for 30 min. The reaction mixture was diluted with dichloromethane, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by preparative thin layer chromatography (eluant: 9:1 hexane/ethyl acetate) to provide methyl 5′-fluoro-2′-nitrobiphenyl-2-carboxylate (37a, 54.8 mg, 0.199 mmol, 56.6% yield). the mixture was reacted in a microwave reactor at 100° C. for 30 min dried over anhydrous sodium sulfate filtered concentrated under reduced pressure The residue was purified by preparative thin layer chromatography (eluant: 9:1 hexane/ethyl acetate)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methyl 6-amino-5-bromonicotinate (500 mg, 2.16 mmol), 2-methoxycarbonylphenylboronic acid (580 mg, 3.25 mmol), palladium(II) acetate (20 mg, 0.09 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (70 mg, 0.17 mmol), and potassium carbonate (900 mg, 6.50 mmol) were dissolved in dioxane/H2O (11 mL, 10/1, v/v), and stirred overnight at 100° C. The reaction mixture was diluted with MeOH, filtered through a membrane plug, and purified via prep-LC-MS to provide 21 (60 mg, 11% yield) as a white solid. LC-MS (M+H=241, obsd.=241). 1H NMR (400 MHz, d6-DMSO): δ 8.98 (d, 1H), 8.87 (d, 1H), 8.48 (d, 1H), 8.32 (dd, 1H), 7.88 (t, 1H), 7.65 (t, 1H). filtered through a membrane plug purified via prep-LC-MS

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methyl 6-amino-5-bromonicotinate (500 mg, 2.16 mmol), 2-methoxycarbonylphenylboronic acid (580 mg, 3.25 mmol), palladium(II) acetate (20 mg, 0.09 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (70 mg, 0.17 mmol), and potassium carbonate (900 mg, 6.50 mmol) were dissolved in dioxane/H2O (11 mL, 10/1, v/v), and stirred overnight at 100° C. The reaction mixture was diluted with MeOH, filtered through a membrane plug, and purified via prep-LC-MS to provide 21 (60 mg, 11% yield) as a white solid. LC-MS (M+H=241, obsd.=241). 1H NMR (400 MHz, d6-DMSO): δ 8.98 (d, 1H), 8.87 (d, 1H), 8.48 (d, 1H), 8.32 (dd, 1H), 7.88 (t, 1H), 7.65 (t, 1H). filtered through a membrane plug purified via prep-LC-MS

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Amino-3-iodo-5-bromopyridine (299 mg, 1.00 mmol), 2-methoxycarbonylphenylboronic acid (189 mg, 1.05 mmol), palladium(II) acetate (9 mg, 0.04 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (33 mg, 0.08 mmol), and potassium carbonate (414 mg, 3.00 mmol) were dissolved in dioxane/H2O (2.0 mL, 10/1, v/v), and stirred overnight at 100° C. The reaction mixture was concentrated, suspended in EtOAc/H2O, and filtered. The precipitate was washed with EtOAc/H2O, and dried under vacuum to provide 1 (6 mg, 7% yield) as a solid. LC-MS (M+H=275, obsd.=275). 1H NMR (400 MHz, d6-DMSO): δ 12.22 (s, 1H), 9.11 (d, 1H), 8.64 (d, 1H), 8.61 (d, 1H), 8.33 (d, 1H), 7.91 (t, 1H), 7.73 (t, 1H). The reaction mixture was concentrated filtered The precipitate was washed with EtOAc/H2O dried under vacuum

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Amino-3-iodo-5-bromopyridine (299 mg, 1.00 mmol), 2-methoxycarbonylphenylboronic acid (189 mg, 1.05 mmol), palladium(II) acetate (9 mg, 0.04 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (33 mg, 0.08 mmol), and potassium carbonate (414 mg, 3.00 mmol) were dissolved in dioxane/H2O (2.0 mL, 10/1, v/v), and stirred overnight at 100° C. The reaction mixture was concentrated, suspended in EtOAc/H2O, and filtered. The precipitate was washed with EtOAc/H2O, and dried under vacuum to provide 1 (6 mg, 7% yield) as a solid. LC-MS (M+H=275, obsd.=275). 1H NMR (400 MHz, d6-DMSO): δ 12.22 (s, 1H), 9.11 (d, 1H), 8.64 (d, 1H), 8.61 (d, 1H), 8.33 (d, 1H), 7.91 (t, 1H), 7.73 (t, 1H). The reaction mixture was concentrated filtered The precipitate was washed with EtOAc/H2O dried under vacuum

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Amino-3-bromopyridine (173 mg, 1.00 mmol), 2-methoxycarbonyl-phenylboronic acid (225 mg, 1.25 mmol), Pd(OAc)2 (9 mg, 0.04 mmol), S-Phos (33 mg, 0.08 mmol), and K2CO3 (414 mg, 3.00 mmol) were dissolved in dioxane/H2O (2.0 mL, 10/1, v/v), and stirred overnight at 100° C. The reaction mixture was concentrated, suspended in EtOAc/H2O, and filtered. The precipitate was washed with EtOAc/H2O, and dried under vacuum to provide 1 (75 mg, 38% yield) as a solid. LC-MS (M+H=197, obsd.=197). 1H NMR (400 MHz, d6-DMSO): δ 12.08 (s, 1H), 8.83 (d, 1H), 8.55 (d, 1H), 8.49 (dd, 1H), 8.42 (d, 1H), 7.90 (t, 1H), 7.70 (t, 1H), 7.33 (dd, 1H). The reaction mixture was concentrated filtered The precipitate was washed with EtOAc/H2O dried under vacuum

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

Procedure: To a microwave vessel was added 2-(methoxycarbonyl)phenylboronic acid (63.4 mg, 0.352 mmol), 2-bromo-4-fluoro-1-nitrobenzene (77 mg, 0.35 mmol), diacetoxypalladium (0.93 mg, 4.1 μmol) and dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (3.47 mg, 8.45 μmol). Ethanol (1760 μl) and sodium carbonate (176 μl, 0.352 mmol) were added and the mixture was reacted in a microwave reactor at 100° C. for 30 min. The reaction mixture was diluted with dichloromethane, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by preparative thin layer chromatography (eluant: 9:1 hexane/ethyl acetate) to provide methyl 5′-fluoro-2′-nitrobiphenyl-2-carboxylate (37a, 54.8 mg, 0.199 mmol, 56.6% yield). the mixture was reacted in a microwave reactor at 100° C. for 30 min dried over anhydrous sodium sulfate filtered concentrated under reduced pressure The residue was purified by preparative thin layer chromatography (eluant: 9:1 hexane/ethyl acetate)

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

Procedure: To a microwave vessel was added 2-(methoxycarbonyl)phenylboronic acid (63.4 mg, 0.352 mmol), 2-bromo-4-fluoro-1-nitrobenzene (77 mg, 0.35 mmol), diacetoxypalladium (0.93 mg, 4.1 mmol) and dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (3.47 mg, 8.45 μmol). Ethanol (1760 μl) and sodium carbonate (176 μl, 0.352 mmol) were added and the mixture was reacted in a microwave reactor at 100° C. for 30 min. The reaction mixture was diluted with dichloromethane, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by preparative thin layer chromatography (eluant: 9:1 hexane/ethyl acetate) to provide methyl 5′-fluoro-2′-nitrobiphenyl-2-carboxylate (37a, 54.8 mg, 0.199 mmol, 56.6% yield). the mixture was reacted in a microwave reactor at 100° C. for 30 min dried over anhydrous sodium sulfate filtered concentrated under reduced pressure The residue was purified by preparative thin layer chromatography (eluant: 9:1 hexane/ethyl acetate)