(3-fluoro-2-methylphenyl)boronic acid

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

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

Procedure: Following the general Suzuki coupling procedure, reaction of bromide 6A (65 mg, 0.2 mmol), 3-fluoro-2-methylphenylboronic acid (46 mg, 0.3 mmol), K2CO3 (82 mg, 0.6 mmol) and Pd(PPh3)4 (5 mg, 0.004 mmol) provided the coupling product as an off-white powder (30 mg, 43% yield). EIMS 354.1 [M+H]+.

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

Procedure: Following the general Suzuki coupling procedure, reaction of bromide 6A (65 mg, 0.2 mmol), 3-fluoro-2-methylphenylboronic acid (46 mg, 0.3 mmol), K2CO3 (82 mg, 0.6 mmol) and Pd(PPh3)4 (5 mg, 0.004 mmol) provided the coupling product as an off-white powder (30 mg, 43% yield). EIMS 354.1 [M+H]+.

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

Procedure: Following the general Suzuki coupling procedure, reaction of bromide 6A (65 mg, 0.2 mmol), 3-fluoro-2-methylphenylboronic acid (46 mg, 0.3 mmol), K2CO3 (82 mg, 0.6 mmol) and Pd(PPh3)4 (5 mg, 0.004 mmol) provided the coupling product as an off-white powder (30 mg, 43% yield). EIMS 354.1 [M+H]+.

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

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

Procedure: A mixture of methyl 4-bromo-3-(methoxymethyl)benzoate (Intermediate 1, Step 2, 5.00 g, 19.3 mmol), 3-fluoro-2-methylphenylboronic acid (4.46 g, 29.0 mmol), bis(triphenylphosphine)palladium(II) chloride (271 mg, 0.39 mmol) and cesium fluoride (8.79 g, 57.9 mmol) was prepared in dioxane (50 mL) and water (20 mL) under nitrogen atmosphere. The reaction mixture was heated at 100° C. for 1 hour. The reaction mixture was cooled at RT, diluted with MTBE (250 mL) and the layers were separated. The organic layer was washed with water (100 mL) and brine (100 mL). The aqueous layers were extracted with MTBE (150 mL). The organic layers were combined, dried over MgSO4 and concentrated under reduced pressure. After purification by flash chromatography (silica, EtOAc/n-hexane), the title compound was obtained as a colorless oil (4.85 g, 87%). HPLC (Method A), Rt 5.0 min (purity: 99.5%). LC/MS (Method B): 289.0 (M+H)+. The reaction mixture was cooled at RT the layers were separated The organic layer was washed with water (100 mL) and brine (100 mL) The aqueous layers were extracted with MTBE (150 mL) dried over MgSO4 concentrated under reduced pressure After purification by flash chromatography (silica, EtOAc/n-hexane)

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

Procedure: A mixture of methyl 4-bromo-3-(methoxymethyl)benzoate (Intermediate 1, Step 2, 5.00 g, 19.3 mmol), 3-fluoro-2-methylphenylboronic acid (4.46 g, 29.0 mmol), bis(triphenylphosphine)palladium(II) chloride (271 mg, 0.39 mmol) and cesium fluoride (8.79 g, 57.9 mmol) was prepared in dioxane (50 mL) and water (20 mL) under nitrogen atmosphere. The reaction mixture was heated at 100° C. for 1 hour. The reaction mixture was cooled at RT, diluted with MTBE (250 mL) and the layers were separated. The organic layer was washed with water (100 mL) and brine (100 mL). The aqueous layers were extracted with MTBE (150 mL). The organic layers were combined, dried over MgSO4 and concentrated under reduced pressure. After purification by flash chromatography (silica, EtOAc/n-hexane), the title compound was obtained as a colorless oil (4.85 g, 87%). HPLC (Method A), Rt 5.0 min (purity: 99.5%). LC/MS (Method B): 289.0 (M+H)+. The reaction mixture was cooled at RT the layers were separated The organic layer was washed with water (100 mL) and brine (100 mL) The aqueous layers were extracted with MTBE (150 mL) dried over MgSO4 concentrated under reduced pressure After purification by flash chromatography (silica, EtOAc/n-hexane)

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

Procedure: A mixture of methyl 4-bromo-3-(methoxymethyl)benzoate (Intermediate 1, Step 2, 5.00 g, 19.3 mmol), 3-fluoro-2-methylphenylboronic acid (4.46 g, 29.0 mmol), bis(triphenylphosphine)palladium(II) chloride (271 mg, 0.39 mmol) and cesium fluoride (8.79 g, 57.9 mmol) was prepared in dioxane (50 mL) and water (20 mL) under nitrogen atmosphere. The reaction mixture was heated at 100° C. for 1 hour. The reaction mixture was cooled at RT, diluted with MTBE (250 mL) and the layers were separated. The organic layer was washed with water (100 mL) and brine (100 mL). The aqueous layers were extracted with MTBE (150 mL). The organic layers were combined, dried over MgSO4 and concentrated under reduced pressure. After purification by flash chromatography (silica, EtOAc/n-hexane), the title compound was obtained as a colorless oil (4.85 g, 87%). HPLC (Method A), Rt 5.0 min (purity: 99.5%). LC/MS (Method B): 289.0 (M+H)+. The reaction mixture was cooled at RT the layers were separated The organic layer was washed with water (100 mL) and brine (100 mL) The aqueous layers were extracted with MTBE (150 mL) dried over MgSO4 concentrated under reduced pressure After purification by flash chromatography (silica, EtOAc/n-hexane)

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

Procedure: A mixture of methyl 4-bromo-3-(methoxymethyl)benzoate (5.00 g, 19.3 mmol), 3-fluoro-2-methylphenylboronic acid (Combi-Blocks BB-3475, 4.46 g, 29.0 mmol), bis(triphenylphosphine)palladium(II) chloride (271 mg, 0.39 mmol) and cesium fluoride (8.79 g, 57.9 mmol) was prepared in dioxane (50 mL) and water (20 mL) under N2 atmosphere. The reaction mixture was heated at 100° C. for 1 hour. The reaction mixture was cooled at RT, diluted with MTBE (250 mL) and the layers were separated. The organic layer was washed with water (100 mL) and brine (100 mL). The aqueous layers were extracted with MTBE (150 mL). The organic layers were combined, dried (MgSO4) and concentrated under reduced pressure. After purification by flash chromatography (silica, EtOAc/n-hexane), the title compound was obtained as a colorless oil (4.85 g, 87%). HPLC (Method A), Rt: 5.0 min (purity: 99.5%). UPLC/MS, M+(ESI): 289.0. The reaction mixture was cooled at RT the layers were separated The organic layer was washed with water (100 mL) and brine (100 mL) The aqueous layers were extracted with MTBE (150 mL) dried (MgSO4) concentrated under reduced pressure After purification by flash chromatography (silica, EtOAc/n-hexane)

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

Procedure: Prepared according to the procedure described in Example 1, Step 10, using 1-{4′-[4-(6-bromo-pyridin-2-ylamino)-3-methyl-isoxazol-5-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid ethyl ester and 3-fluoro-2-methyl-phenylboronic acid. Additionally, (1,1′-bis(diphenylphosphino)ferrocene)-dichloropalladium(II) was used as the catalyst in place of tetrakis(triphenylphosphine)palladium(0). Prepared

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-fluoro-2-methylbenzeneboronic acid were coupled in the same way as in Example 30 to give 2-[3-(2,3′-difluoro-2′-methylbiphenyl-5-yl)-8-fluoroimidazo[1,2-α]pyridin-7-yl]propan-2-ol as an off-white solid (8 mg, 7%): m/z (ES+) 397 [MH+].

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

Procedure: Following the general Suzuki coupling procedure, reaction of bromide 6A (65 mg, 0.2 mmol), 3-fluoro-2-methylphenylboronic acid (46 mg, 0.3 mmol), K2CO3 (82 mg, 0.6 mmol) and Pd(PPh3)4 (5 mg, 0.004 mmol) provided the coupling product as an off-white powder (30 mg, 43% yield). EIMS 354.1 [M+H]+.