(3-chloro-2-methylphenyl)boronic acid

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

Procedure: To a solution of 10.0 g (48.7 mmol) 2-bromo-6-chlorotoluene and 11.3 ml (48.7 mmol) triisopropyl borate in 90 ml dry THF were added dropwise 30 ml (49 mmol) of a 1.6 M solution on n-butyllithium in hexanes at −78° C. under argon. After 45 min the reaction mixture was allowed to warm to room temperature. The reaction was quenched by addition of 5 ml water and the solvent was evaporated in vacuo. Addition of 1 M aqueous hydrochloric acid solution was followed by extraction with four portions of dichloromethane. The combined organic extracts were dried over sodium sulfate and concentrated in vacuo. Crystallisation from heptane gave 5.08 g (61%) of the title compound as a white solid. The reaction was quenched by addition of 5 ml water the solvent was evaporated in vacuo Addition of 1 M aqueous hydrochloric acid solution was followed by extraction with four portions of dichloromethane The combined organic extracts were dried over sodium sulfate concentrated in vacuo Crystallisation from heptane

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

Procedure: To a solution of 10.0 g (48.7 mmol) 2-bromo-6-chlorotoluene and 11.3 ml (48.7 mmol) triisopropyl borate in 90 ml dry THF were added dropwise 30 ml (49 mmol) of a 1.6 M solution on n-butyllithium in hexanes at −78° C. under argon. After 45 min the reaction mixture was allowed to warm to room temperature. The reaction was quenched by addition of 5 ml water and the solvent was evaporated in vacuo. Addition of 1 M aqueous hydrochloric acid solution was followed by extraction with four portions of dichloromethane. The combined organic extracts were dried over sodium sulfate and concentrated in vacuo. Crystallisation from heptane gave 5.08 g (61%) of the title compound as a white solid. The reaction was quenched by addition of 5 ml water the solvent was evaporated in vacuo Addition of 1 M aqueous hydrochloric acid solution was followed by extraction with four portions of dichloromethane The combined organic extracts were dried over sodium sulfate concentrated in vacuo Crystallisation from heptane

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

Procedure: The title compound was prepared by the method of Example 89 step C from tert-butyl(6aS,10aR)-2-bromo-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)carboxylate (189 mg, 0.5 mmol) and 3-chloro-2-methylphenylboronic acid (140 mg, 1.0 mmol) to afford after chromatographic purification the title compound (99 mg, 47%). 1H NMR (CDCl3, 300 MHz) δ 7.28–7.31 (m, 1H), 7.10 (d, 2H, J=4.4 Hz), 6.85 (s, 1H), 6.81 (s, 1H), 3.82–4.24 (m, 2H), 3.64–3.74 (m, 1H), 3.24–3.54 (m, 4H), 2.86–3.26 (m, 3H), 1.86 (s, 3H),1.84–1.89 (m, 2H), 1.48 (s, 9H) ppm. MS-ApCI: 425 [M+H+]. to afford after chromatographic purification the title compound (99 mg, 47%)

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

Procedure: The title compound was prepared by the method of Example 89 step C from tert-butyl (6aS,10aR)-2-bromo-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH) carboxylate (189 mg, 0.5 mmol) and 3-chloro-2-methylphenylboronic acid (140 mg, 1.0 mmol) to afford after chromatographic purification the title compound (99 mg, 47%). 1H NMR (CDCl3, 300 MHz) δ 7.28-7.31 (m, 1H), 7.10 (d, 2H, J=4.4 Hz), 6.85 (s, 1H), 6.81 (s, 1H), 3.82-4.24 (m, 2H), 3.64-3.74 (m, 1H), 3.24-3.54 (m, 4H), 2.86-3.26 (m, 3H), 1.86 (s, 3H), 1.84-1.89 (m, 2H), 1.48 (s, 9H) ppm. MS-ApCI: 425 [M+H+]. to afford after chromatographic purification the title compound (99 mg, 47%)

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

Procedure: The title compound was prepared by the method of Example 89 step C from tert-butyl (6aS,10aR)-2-bromo-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH) carboxylate (189 mg, 0.5 mmol) and 3-chloro-2-methylphenylboronic acid (140 mg, 1.0 mmol) to afford after chromatographic purification the title compound (99 mg, 47%). 1H NMR (CDCl3, 300 MHz) δ7.28-7.31 (m, 1H), 7.10 (d, 2H, J=4.4 Hz), 6.85 (s, 1H), 6.81 (s, 1H), 3.82-4.24 (m, 2H), 3.64-3.74 (m, 1H), 3.24-3.54 (m, 4H), 2.86-3.26 (m, 3H), 1.86 (s, 3H),1.84-1.89 (m, 2H), 1.48 (s, 9H) ppm. MS-ApCI: 425 [M+H+]. to afford after chromatographic purification the title compound (99 mg, 47%)

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

Procedure: 2-[3-(3-Chloro-4-fluorophenyl)-8-fluoroimidazo[1,2-α]pyridin-7-yl]-propan-2-ol and 3-chloro-2-methylbenzeneboronic acid were coupled in the same way as in Example 30 to give 2-[3-(3′-chloro-2-fluoro-2′-methylbiphenyl-5-yl)-8-fluoroimidazo[1,2-α]pyridin-7-yl]propan-2-ol as an off-white solid (5 mg, 4%): m/z (ES+) 413 [MH+].

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

Procedure: To a solution of 10.0 g (48.7 mmol) 2-bromo-6-chlorotoluene and 11.3 ml (48.7 mmol) triisopropyl borate in 90 ml dry THF were added dropwise 30 ml (49 mmol) of a 1.6 M solution on n-butyllithium in hexanes at −78° C. under argon. After 45 min the reaction mixture was allowed to warm to room temperature. The reaction was quenched by addition of 5 ml water and the solvent was evaporated in vacuo. Addition of 1 M aqueous hydrochloric acid solution was followed by extraction with four portions of dichloromethane. The combined organic extracts were dried over sodium sulfate and concentrated in vacuo. Crystallisation from heptane gave 5.08 g (61%) of the title compound as a white solid. The reaction was quenched by addition of 5 ml water the solvent was evaporated in vacuo Addition of 1 M aqueous hydrochloric acid solution was followed by extraction with four portions of dichloromethane The combined organic extracts were dried over sodium sulfate concentrated in vacuo Crystallisation from heptane