5-CHLORO-2-FLUORO-3-METHYLPHENYLBORONIC&

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

Procedure: A 4 mL vial was charged with a stir bar, a solution of Example 41A (27.50 mg, 0.09 mmol) in 1 mL of ethanol, a solution of (5-chloro-2-fluoro-3-methylphenyl)boronic acid (24.85 mg, 1.5 eq, 0.13 mmol) in 220 μL of ethanol, a 1.0 M aqueous solution of cesium carbonate (175.84 μL, 2 eq, 0.18 mmol), and Siliacat® DPP-Pd (Silicycle®, 0.27 mmol/g loading, 32.56 mg). The loaded vial was seal capped and placed in an Anton Paar Synthos 3000 microwave reactor (900 W maximum) and heated to 120° C. for 15 minutes. Upon completion, the solids were collected by filtration and dried under vacuum. The dried material was then re-dissolved in 1.4 mL of dimethyl sulfoxide/methanol 1:1 (v/v) solution, and purified by preparative HPLC on a Phenomenex® Luna® C8(2) 5 μm 100A AXIA™ column (30 mm×75 mm) A gradient of acetonitrile (A) and 0.1% trifluoroacetic acid in water (B) was used, at a flow rate of 50 mL/minute (0-0.5 minutes 10% A, 0.5-6.0 minutes linear gradient 10-100% A, 6.0-7.0 minutes 100% A, 7.0-8.0 minutes linear gradient 100-10% A) to yield the title compound. 1H NMR (400 MHz, DMSO-d6/D2O) δ 2.37 (d, J=2.1 Hz, 3H), 2.65 (s, 2H), 2.95 (d, J=5.2 Hz, 3H), 3.18 (s, 1H), 3.40 (t, J=5.7 Hz, 2H), 3.95 (d, J=3.4 Hz, 2H), 6.57 (d, J=3.8 Hz, 1H), 6.59-6.64 (m, 1H), 7.60 (d, J=5.8 Hz, 2H), 8.85 (s, 1H). MS (ESI+) m/z 421.1 (M+H)+. Examples 42 through 59 were prepared essentially as described in Example 41B, substituting the appropriate boronic acid. A 4 mL vial was charged with a stir bar The loaded vial was seal capped Upon completion, the solids were collected by filtration dried under vacuum The dried material was then re-dissolved in 1.4 mL of dimethyl sulfoxide/methanol 1:1 (v/v) solution purified by preparative HPLC on a Phenomenex® Luna® C8(2) 5 μm 100A AXIA™ column (30 mm×75 mm) A gradient of acetonitrile (A) and 0.1% trifluoroacetic acid in water (B) was used, at a flow rate of 50 mL/minute (0-0.5 minutes 10% A, 0.5-6.0 minutes linear gradient 10-100% A, 6.0-7.0 minutes 100% A, 7.0-8.0 minutes linear gradient 100-10% A)

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

Procedure: A 4 mL vial was charged with a stir bar, a solution of Example 41A (27.50 mg, 0.09 mmol) in 1 mL of ethanol, a solution of (5-chloro-2-fluoro-3-methylphenyl)boronic acid (24.85 mg, 1.5 eq, 0.13 mmol) in 220 μL of ethanol, a 1.0 M aqueous solution of cesium carbonate (175.84 μL, 2 eq, 0.18 mmol), and Siliacat® DPP-Pd (Silicycle®, 0.27 mmol/g loading, 32.56 mg). The loaded vial was seal capped and placed in an Anton Paar Synthos 3000 microwave reactor (900 W maximum) and heated to 120° C. for 15 minutes. Upon completion, the solids were collected by filtration and dried under vacuum. The dried material was then re-dissolved in 1.4 mL of dimethyl sulfoxide/methanol 1:1 (v/v) solution, and purified by preparative HPLC on a Phenomenex® Luna® C8(2) 5 μm 100A AXIA™ column (30 mm×75 mm) A gradient of acetonitrile (A) and 0.1% trifluoroacetic acid in water (B) was used, at a flow rate of 50 mL/minute (0-0.5 minutes 10% A, 0.5-6.0 minutes linear gradient 10-100% A, 6.0-7.0 minutes 100% A, 7.0-8.0 minutes linear gradient 100-10% A) to yield the title compound. 1H NMR (400 MHz, DMSO-d6/D2O) δ 2.37 (d, J=2.1 Hz, 3H), 2.65 (s, 2H), 2.95 (d, J=5.2 Hz, 3H), 3.18 (s, 1H), 3.40 (t, J=5.7 Hz, 2H), 3.95 (d, J=3.4 Hz, 2H), 6.57 (d, J=3.8 Hz, 1H), 6.59-6.64 (m, 1H), 7.60 (d, J=5.8 Hz, 2H), 8.85 (s, 1H). MS (ESI+) m/z 421.1 (M+H)+. Examples 42 through 59 were prepared essentially as described in Example 41B, substituting the appropriate boronic acid. A 4 mL vial was charged with a stir bar The loaded vial was seal capped Upon completion, the solids were collected by filtration dried under vacuum The dried material was then re-dissolved in 1.4 mL of dimethyl sulfoxide/methanol 1:1 (v/v) solution purified by preparative HPLC on a Phenomenex® Luna® C8(2) 5 μm 100A AXIA™ column (30 mm×75 mm) A gradient of acetonitrile (A) and 0.1% trifluoroacetic acid in water (B) was used, at a flow rate of 50 mL/minute (0-0.5 minutes 10% A, 0.5-6.0 minutes linear gradient 10-100% A, 6.0-7.0 minutes 100% A, 7.0-8.0 minutes linear gradient 100-10% A)

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

Procedure: A 4 mL vial was charged with a stir bar, a solution of Example 41A (27.50 mg, 0.09 mmol) in 1 mL of ethanol, a solution of (5-chloro-2-fluoro-3-methylphenyl)boronic acid (24.85 mg, 1.5 eq, 0.13 mmol) in 220 μL of ethanol, a 1.0 M aqueous solution of cesium carbonate (175.84 μL, 2 eq, 0.18 mmol), and Siliacat® DPP-Pd (Silicycle®, 0.27 mmol/g loading, 32.56 mg). The loaded vial was seal capped and placed in an Anton Paar Synthos 3000 microwave reactor (900 W maximum) and heated to 120° C. for 15 minutes. Upon completion, the solids were collected by filtration and dried under vacuum. The dried material was then re-dissolved in 1.4 mL of dimethyl sulfoxide/methanol 1:1 (v/v) solution, and purified by preparative HPLC on a Phenomenex® Luna® C8(2) 5 μm 100A AXIA™ column (30 mm×75 mm) A gradient of acetonitrile (A) and 0.1% trifluoroacetic acid in water (B) was used, at a flow rate of 50 mL/minute (0-0.5 minutes 10% A, 0.5-6.0 minutes linear gradient 10-100% A, 6.0-7.0 minutes 100% A, 7.0-8.0 minutes linear gradient 100-10% A) to yield the title compound. 1H NMR (400 MHz, DMSO-d6/D2O) δ 2.37 (d, J=2.1 Hz, 3H), 2.65 (s, 2H), 2.95 (d, J=5.2 Hz, 3H), 3.18 (s, 1H), 3.40 (t, J=5.7 Hz, 2H), 3.95 (d, J=3.4 Hz, 2H), 6.57 (d, J=3.8 Hz, 1H), 6.59-6.64 (m, 1H), 7.60 (d, J=5.8 Hz, 2H), 8.85 (s, 1H). MS (ESI+) m/z 421.1 (M+H)+. Examples 42 through 59 were prepared essentially as described in Example 41B, substituting the appropriate boronic acid. A 4 mL vial was charged with a stir bar The loaded vial was seal capped Upon completion, the solids were collected by filtration dried under vacuum The dried material was then re-dissolved in 1.4 mL of dimethyl sulfoxide/methanol 1:1 (v/v) solution purified by preparative HPLC on a Phenomenex® Luna® C8(2) 5 μm 100A AXIA™ column (30 mm×75 mm) A gradient of acetonitrile (A) and 0.1% trifluoroacetic acid in water (B) was used, at a flow rate of 50 mL/minute (0-0.5 minutes 10% A, 0.5-6.0 minutes linear gradient 10-100% A, 6.0-7.0 minutes 100% A, 7.0-8.0 minutes linear gradient 100-10% A)