4-bromo-N-propan-2-ylbenzamide

Conditions: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-bromo-N-isopropylbenzamide (1.82 g, 7.52 mmol), {3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile hydrogen chloride (2.23 g, 5.00 mmol), palladium acetate (78 mg, 0.35 mmol, Aldrich [3375-31-3]), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (405 mg, 0.700 mmol, Aldrich [161265-03-8]), and cesium carbonate (3.03 g, 9.30 mmol) in toluene (22 mL) was de-gassed and purged several times with N2 (g) prior to heating at 105° C. in a sealed vial for 2 days. Upon cooling to room temperature the reaction mixture was filtered through a pad of celite, concentrated in-vacuo and purified by flash chromatography on a silica gel column eluting with MeOH in methylene chloride (0-5%) to afford the desired product (1.74 g, 61% yield). LCMS (M+H)+: m/z=571.3. was de-gassed purged several times with N2 (g) Upon cooling to room temperature the reaction mixture was filtered through a pad of celite concentrated in-vacuo purified by flash chromatography on a silica gel column eluting with MeOH in methylene chloride (0-5%)

Conditions: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-bromo-N-isopropylbenzamide (1.82 g, 7.52 mmol), {3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile hydrogen chloride (2.23 g, 5.00 mmol), palladium acetate (78 mg, 0.35 mmol, Aldrich [3375-31-3]), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (405 mg, 0.700 mmol, Aldrich [161265-03-8]), and cesium carbonate (3.03 g, 9.30 mmol) in toluene (22 mL) was de-gassed and purged several times with N2 (g) prior to heating at 105° C. in a sealed vial for 2 days. Upon cooling to room temperature the reaction mixture was filtered through a pad of celite, concentrated in-vacuo and purified by flash chromatography on a silica gel column eluting with MeOH in methylene chloride (0-5%) to afford the desired product (1.74 g, 61% yield). LCMS (M+H)+: m/z=571.3. was de-gassed purged several times with N2 (g) Upon cooling to room temperature the reaction mixture was filtered through a pad of celite concentrated in-vacuo purified by flash chromatography on a silica gel column eluting with MeOH in methylene chloride (0-5%)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-bromobenzoic acid (4.00 g, 19.9 mmol, Aldrich: Cat. #108510) and thionyl chloride (10.0 mL, 137 mmol) was heated by microwave irradiation at 100° C. for 1 h, turning the heterogeneous solution to a homogeneous solution. The volatiles were removed in vacuo and the residue was azeotropically washed with dry acetonitrile several times (20 mL×4) to remove excess thionyl chloride. The residue was dissolved in anhydrous methylene chloride (40 mL) and cooled to 0° C. prior to the addition of 2-propanamine (8.0 mL, 94 mmol, 99.5% pure Aldrich [75-31-0]). After 1 hour, the reaction mixture was diluted with methylene chloride (20 mL) and quenched with H2O (5 mL). The layers were separated and the organic layer was washed with H2O (1×5 mL), saturated NaHCO3 (1×5 mL), H2O (1×5 mL), 1 N HCl (3×5 mL), H2O (1×5 mL), and brine (5 mL). The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo to afford the desired product (4.50 g, 93% yield) which was used directly in the next step without further purification. LCMS (M+H)+: m/z=242/244. The volatiles were removed in vacuo the residue was azeotropically washed with dry acetonitrile several times (20 mL×4) to remove excess thionyl chloride The residue was dissolved in anhydrous methylene chloride (40 mL) quenched with H2O (5 mL) The layers were separated the organic layer was washed with H2O (1×5 mL), saturated NaHCO3 (1×5 mL), H2O (1×5 mL), 1 N HCl (3×5 mL), H2O (1×5 mL), and brine (5 mL) The organic layer was dried over Na2SO4 filtered concentrated in vacuo

Conditions: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-bromo-N-isopropylbenzamide (1.82 g, 7.52 mmol), {3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile hydrogen chloride (2.23 g, 5.00 mmol), palladium acetate (78 mg, 0.35 mmol, Aldrich [3375-31-3]), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (405 mg, 0.700 mmol, Aldrich [161265-03-8]), and cesium carbonate (3.03 g, 9.30 mmol) in toluene (22 mL) was de-gassed and purged several times with N2 (g) prior to heating at 105° C. in a sealed vial for 2 days. Upon cooling to room temperature the reaction mixture was filtered through a pad of celite, concentrated in-vacuo and purified by flash chromatography on a silica gel column eluting with MeOH in methylene chloride (0-5%) to afford the desired product (1.74 g, 61% yield). LCMS (M+H)+: m/z=571.3. was de-gassed purged several times with N2 (g) Upon cooling to room temperature the reaction mixture was filtered through a pad of celite concentrated in-vacuo purified by flash chromatography on a silica gel column eluting with MeOH in methylene chloride (0-5%)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-bromobenzoic acid (4.00 g, 19.9 mmol, Aldrich: Cat. #108510) and thionyl chloride (10.0 mL, 137 mmol) was heated by microwave irradiation at 100° C. for 1 h, turning the heterogeneous solution to a homogeneous solution. The volatiles were removed in vacuo and the residue was azeotropically washed with dry acetonitrile several times (20 mL×4) to remove excess thionyl chloride. The residue was dissolved in anhydrous methylene chloride (40 mL) and cooled to 0° C. prior to the addition of 2-propanamine (8.0 mL, 94 mmol, 99.5% pure Aldrich [75-31-0]). After 1 hour, the reaction mixture was diluted with methylene chloride (20 mL) and quenched with H2O (5 mL). The layers were separated and the organic layer was washed with H2O (1×5 mL), saturated NaHCO3 (1×5 mL), H2O (1×5 mL), 1 N HCl (3×5 mL), H2O (1×5 mL), and brine (5 mL). The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo to afford the desired product (4.50 g, 93% yield) which was used directly in the next step without further purification. LCMS (M+H)+: m/z=242/244. The volatiles were removed in vacuo the residue was azeotropically washed with dry acetonitrile several times (20 mL×4) to remove excess thionyl chloride The residue was dissolved in anhydrous methylene chloride (40 mL) quenched with H2O (5 mL) The layers were separated the organic layer was washed with H2O (1×5 mL), saturated NaHCO3 (1×5 mL), H2O (1×5 mL), 1 N HCl (3×5 mL), H2O (1×5 mL), and brine (5 mL) The organic layer was dried over Na2SO4 filtered concentrated in vacuo

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-bromobenzoic acid (4.00 g, 19.9 mmol, Aldrich: Cat. #108510) and thionyl chloride (10.0 mL, 137 mmol) was heated by microwave irradiation at 100° C. for 1 h, turning the heterogeneous solution to a homogeneous solution. The volatiles were removed in vacuo and the residue was azeotropically washed with dry acetonitrile several times (20 mL×4) to remove excess thionyl chloride. The residue was dissolved in anhydrous methylene chloride (40 mL) and cooled to 0° C. prior to the addition of 2-propanamine (8.0 mL, 94 mmol, 99.5% pure Aldrich [75-31-0]). After 1 hour, the reaction mixture was diluted with methylene chloride (20 mL) and quenched with H2O (5 mL). The layers were separated and the organic layer was washed with H2O (1×5 mL), saturated NaHCO3 (1×5 mL), H2O (1×5 mL), 1 N HCl (3×5 mL), H2O (1×5 mL), and brine (5 mL). The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo to afford the desired product (4.50 g, 93% yield) which was used directly in the next step without further purification. LCMS (M+H)+: m/z=242/244. The volatiles were removed in vacuo the residue was azeotropically washed with dry acetonitrile several times (20 mL×4) to remove excess thionyl chloride The residue was dissolved in anhydrous methylene chloride (40 mL) quenched with H2O (5 mL) The layers were separated the organic layer was washed with H2O (1×5 mL), saturated NaHCO3 (1×5 mL), H2O (1×5 mL), 1 N HCl (3×5 mL), H2O (1×5 mL), and brine (5 mL) The organic layer was dried over Na2SO4 filtered concentrated in vacuo

Conditions: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-bromo-N-isopropylbenzamide (1.82 g, 7.52 mmol), {3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile hydrogen chloride (2.23 g, 5.00 mmol), palladium acetate (78 mg, 0.35 mmol, Aldrich [3375-31-3]), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (405 mg, 0.700 mmol, Aldrich [161265-03-8]), and cesium carbonate (3.03 g, 9.30 mmol) in toluene (22 mL) was de-gassed and purged several times with N2 (g) prior to heating at 105° C. in a sealed vial for 2 days. Upon cooling to room temperature the reaction mixture was filtered through a pad of celite, concentrated in-vacuo and purified by flash chromatography on a silica gel column eluting with MeOH in methylene chloride (0-5%) to afford the desired product (1.74 g, 61% yield). LCMS (M+H)+: m/z=571.3. was de-gassed purged several times with N2 (g) Upon cooling to room temperature the reaction mixture was filtered through a pad of celite concentrated in-vacuo purified by flash chromatography on a silica gel column eluting with MeOH in methylene chloride (0-5%)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-bromobenzoic acid (4.00 g, 19.9 mmol, Aldrich: Cat. #108510) and thionyl chloride (10.0 mL, 137 mmol) was heated by microwave irradiation at 100° C. for 1 h, turning the heterogeneous solution to a homogeneous solution. The volatiles were removed in vacuo and the residue was azeotropically washed with dry acetonitrile several times (20 mL×4) to remove excess thionyl chloride. The residue was dissolved in anhydrous methylene chloride (40 mL) and cooled to 0° C. prior to the addition of 2-propanamine (8.0 mL, 94 mmol, 99.5% pure Aldrich [75-31-0]). After 1 hour, the reaction mixture was diluted with methylene chloride (20 mL) and quenched with H2O (5 mL). The layers were separated and the organic layer was washed with H2O (1×5 mL), saturated NaHCO3 (1×5 mL), H2O (1×5 mL), 1 N HCl (3×5 mL), H2O (1×5 mL), and brine (5 mL). The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo to afford the desired product (4.50 g, 93% yield) which was used directly in the next step without further purification. LCMS (M+H)+: m/z=242/244. The volatiles were removed in vacuo the residue was azeotropically washed with dry acetonitrile several times (20 mL×4) to remove excess thionyl chloride The residue was dissolved in anhydrous methylene chloride (40 mL) quenched with H2O (5 mL) The layers were separated the organic layer was washed with H2O (1×5 mL), saturated NaHCO3 (1×5 mL), H2O (1×5 mL), 1 N HCl (3×5 mL), H2O (1×5 mL), and brine (5 mL) The organic layer was dried over Na2SO4 filtered concentrated in vacuo