(2-bromo-3-methylphenyl)-(oxolan-2-yl)methanone

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-morpholino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine (0.099 g, 0.279 mmol), (2-bromo-3-methylphenyl)(tetrahydrofuran-2-yl)methanone (0.050 g, 0.186 mmol), potassium phosphate tribasic (0.077 mL, 0.929 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (0.018 g, 0.037 mmol), and Pd2(dba)3 (8.51 mg, 9.29 μmol) were treated with dioxane (1.2 mL) and water (0.62 mL) in a medium-sized Smith synthesizer vial. The mixture was heated to 140° C. for 12 min in a microwave reactor. The reaction mixture was filtered then partitioned between EtOAc and water, organics were washed with water and brine and then concentrated in vacuo. The crude product was purified by silica flash chromatography (1-10% MeOH/DCM) and then by HPLC (10-75% acetonitril/H2O; TFA modifier). A single fraction was treated with NH4OH, concentrated, filtered and air-dried to afford (2-(2-amino-3-morpholinoquinolin-6-yl)-3-methylphenyl)(tetrahydrofuran-2-yl)methanone. MS (ESI, pos. ion) m/z: 418 (M+1). The reaction mixture was filtered then partitioned between EtOAc and water organics were washed with water and brine concentrated in vacuo The crude product was purified by silica flash chromatography (1-10% MeOH/DCM) A single fraction was treated with NH4OH concentrated filtered air-dried

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

Procedure: A solution of (2-bromo-3-methylphenyl)(4,5-dihydrofuran-2-yl)methanone (0.80 g, 2.99 mmol) (mass approximate, based on ˜8 mg/mL Et2O solution) was treated with 500 mL EtOAc and concentrated to ˜100 mL twice. The resulting solution was placed under N2 atmosphere, treated with 5% Pt/C, and then placed under a balloon of H2. Reaction mixture was allowed to stir overnight, then filtered through plug of celite and the filter agent was further washed with 100 mL EtOAc. The solution was concentrated in vacuo and the crude material was absorbed onto a plug of silica gel and purified by column chromatography eluting with a gradient of 20-100% Et2O in hexane to afford (2-bromo-3-methylphenyl)(tetrahydrofuran-2-yl)methanone. concentrated to ˜100 mL twice treated with 5% Pt/C Reaction mixture filtered through plug of celite the filter agent was further washed with 100 mL EtOAc The solution was concentrated in vacuo the crude material was absorbed onto a plug of silica gel purified by column chromatography eluting with a gradient of 20-100% Et2O in hexane

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

Procedure: A solution of (2-bromo-3-methylphenyl)(4,5-dihydrofuran-2-yl)methanone (0.80 g, 2.99 mmol) (mass approximate, based on ˜8 mg/mL Et2O solution) was treated with 500 mL EtOAc and concentrated to ˜100 mL twice. The resulting solution was placed under N2 atmosphere, treated with 5% Pt/C, and then placed under a balloon of H2. Reaction mixture was allowed to stir overnight, then filtered through plug of celite and the filter agent was further washed with 100 mL EtOAc. The solution was concentrated in vacuo and the crude material was absorbed onto a plug of silica gel and purified by column chromatography eluting with a gradient of 20-100% Et2O in hexane to afford (2-bromo-3-methylphenyl)(tetrahydrofuran-2-yl)methanone. concentrated to ˜100 mL twice treated with 5% Pt/C Reaction mixture filtered through plug of celite the filter agent was further washed with 100 mL EtOAc The solution was concentrated in vacuo the crude material was absorbed onto a plug of silica gel purified by column chromatography eluting with a gradient of 20-100% Et2O in hexane

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-morpholino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine (0.099 g, 0.279 mmol), (2-bromo-3-methylphenyl)(tetrahydrofuran-2-yl)methanone (0.050 g, 0.186 mmol), potassium phosphate tribasic (0.077 mL, 0.929 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (0.018 g, 0.037 mmol), and Pd2(dba)3 (8.51 mg, 9.29 μmol) were treated with dioxane (1.2 mL) and water (0.62 mL) in a medium-sized Smith synthesizer vial. The mixture was heated to 140° C. for 12 min in a microwave reactor. The reaction mixture was filtered then partitioned between EtOAc and water, organics were washed with water and brine and then concentrated in vacuo. The crude product was purified by silica flash chromatography (1-10% MeOH/DCM) and then by HPLC (10-75% acetonitril/H2O; TFA modifier). A single fraction was treated with NH4OH, concentrated, filtered and air-dried to afford (2-(2-amino-3-morpholinoquinolin-6-yl)-3-methylphenyl)(tetrahydrofuran-2-yl)methanone. MS (ESI, pos. ion) m/z: 418 (M+1). The reaction mixture was filtered then partitioned between EtOAc and water organics were washed with water and brine concentrated in vacuo The crude product was purified by silica flash chromatography (1-10% MeOH/DCM) A single fraction was treated with NH4OH concentrated filtered air-dried

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

Procedure: A solution of (2-bromo-3-methylphenyl)(4,5-dihydrofuran-2-yl)methanone (0.80 g, 2.99 mmol) (mass approximate, based on ˜8 mg/mL Et2O solution) was treated with 500 mL EtOAc and concentrated to ˜100 mL twice. The resulting solution was placed under N2 atmosphere, treated with 5% Pt/C, and then placed under a balloon of H2. Reaction mixture was allowed to stir overnight, then filtered through plug of celite and the filter agent was further washed with 100 mL EtOAc. The solution was concentrated in vacuo and the crude material was absorbed onto a plug of silica gel and purified by column chromatography eluting with a gradient of 20-100% Et2O in hexane to afford (2-bromo-3-methylphenyl)(tetrahydrofuran-2-yl)methanone. concentrated to ˜100 mL twice treated with 5% Pt/C Reaction mixture filtered through plug of celite the filter agent was further washed with 100 mL EtOAc The solution was concentrated in vacuo the crude material was absorbed onto a plug of silica gel purified by column chromatography eluting with a gradient of 20-100% Et2O in hexane