2-bromopentan-3-one

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

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of methyl 3-hydroxy-4-methoxy benzoate (19.3 g), 2-bromo-3-pentanone (19.2 ml), potassium carbonate (29.3 g), and DMF (193 ml) was stirred at 90° C. for 2 hours. After being allowed to stand for cooling, water was added to the mixture followed by extraction with toluene. The organic layer was washed with a saturated saline and dried over sodium sulfate, and the solvent was distilled off. The residue was purified by column chromatography (silica gel, hexane:ethyl acetate=3:1) to give Compound IIk-a (25.8 g, 91.5%) as a colorless oily substance. for cooling followed by extraction with toluene The organic layer was washed with a saturated saline dried over sodium sulfate the solvent was distilled off The residue was purified by column chromatography (silica gel, hexane:ethyl acetate=3:1) to give Compound IIk-a (25.8 g, 91.5%) as a colorless oily substance

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5-bromo-2-methoxyphenol (50.0 g), 2-bromo-3-pentanone (68.1 g), potassium carbonate (52.8 g), and DMF (500 ml) was stirred at 70° C. for 2 hours. After being allowed to stand for cooling, water was added to the mixture followed by extraction with ether. The organic layer was washed with a saturated saline and dried over anhydrous magnesium sulfate, and the solvent was distilled off. The residue was purified by silica gel column chromatography (hexane:chloroform=1:1) to give Compound IIb-a (86.8 g, 94.0%) as a pale-yellow oily substance. for cooling followed by extraction with ether The organic layer was washed with a saturated saline dried over anhydrous magnesium sulfate the solvent was distilled off The residue was purified by silica gel column chromatography (hexane:chloroform=1:1) to give Compound IIb-a (86.8 g, 94.0%) as a pale-yellow oily substance

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5-bromo-2-methoxyphenol (50.0 g), 2-bromo-3-pentanone (68.1 g), potassium carbonate (52.8 g), and DMF (500 ml) was stirred at 70° C. for 2 hours. After being allowed to stand for cooling, water was added to the mixture followed by extraction with ether. The organic layer was washed with a saturated saline and dried over anhydrous magnesium sulfate, and the solvent was distilled off. The residue was purified by silica gel column chromatography (hexane:chloroform=1:1) to give Compound IIb-a (86.8 g, 94.0%) as a pale-yellow oily substance. for cooling followed by extraction with ether The organic layer was washed with a saturated saline dried over anhydrous magnesium sulfate the solvent was distilled off The residue was purified by silica gel column chromatography (hexane:chloroform=1:1) to give Compound IIb-a (86.8 g, 94.0%) as a pale-yellow oily substance

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

Procedure: H181 (150 mg, 1.0 mmol) was dissolved in DMF (6.0 mL) and cooled to 0° C. with ice bath. To this solution under nitrogen were added in sequence NaH (60% in mineral oil, 160 mg, 4.0 mmol) and 2-bromopentan-3-one (660.12 mg, 4.0 mmol). The reaction mixture was stirred for 1 d then treated with 1.0 M HCl (10.0 mL). After extraction with ethyl acetate, the organic phase was washed with water and brine, and dried over anhydrous Na2SO4. The residue after rotary evaporation was purified by column chromatography over silica gel to give the title compound (88.9 mg, 38% yield). 1H NMR (400 MHz, CDCl3): δ 7.21 (d, J=8.1 Hz, 1H), 7.06 (d, J=2.4 Hz, 1H), 6.98 (dd, J=8.4 & 2.7 Hz, 1H), 5.00 (s, 2H), 4.67 (q, J=6.8 Hz, 1H), 2.73-2.61 (m, 1H), 2.49-2.39 (m, 1H), 1.47 (d, J=6.8 Hz, 3H) and 0.99 (t, J=7.2 Hz, 3H) ppm; Mp: 72-74° C. After extraction with ethyl acetate the organic phase was washed with water and brine dried over anhydrous Na2SO4 The residue after rotary evaporation was purified by column chromatography over silica gel

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

Procedure: H181 (150 mg, 1.0 mmol) was dissolved in DMF (6.0 mL) and cooled to 0° C. with ice bath. To this solution under nitrogen were added in sequence NaH (60% in mineral oil, 160 mg, 4.0 mmol) and 2-bromopentan-3-one (660.12 mg, 4.0 mmol). The reaction mixture was stirred for 1 d then treated with 1.0 M HCl (10.0 mL). After extraction with ethyl acetate, the organic phase was washed with water and brine, and dried over anhydrous Na2SO4. The residue after rotary evaporation was purified by column chromatography over silica gel to give the title compound (88.9 mg, 38% yield). 1H NMR (400 MHz, CDCl3): δ 7.21 (d, J=8.1 Hz, 1H), 7.06 (d, J=2.4 Hz, 1H), 6.98 (dd, J=8.4 & 2.7 Hz, 1H), 5.00 (s, 2H), 4.67 (q, J=6.8 Hz, 1H), 2.73-2.61 (m, 1H), 2.49-2.39 (m, 1H), 1.47 (d, J=6.8 Hz, 3H) and 0.99 (t, J=7.2 Hz, 3H) ppm; Mp: 72-74° C. After extraction with ethyl acetate the organic phase was washed with water and brine dried over anhydrous Na2SO4 The residue after rotary evaporation was purified by column chromatography over silica gel

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-fluorophenol (8.0 g, 71.4 mmol) in dimethylformamide (130.0 mL) was added potassium carbonate (13.5 g, 97.4 mmol) and 2-bromopentan-3-one (836) (10.7 g, 64.9 mmol). The suspension was heated at 70° C. for 18 h, cooled to room temperature, diluted with water (50 mL), and extracted with ethyl acetate (2×25 mL). The organic layers were combined, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by chromatography (0-20% EtOAc in hexanes) to provide the desired 2-(4-fluorophenoxy)pentan-3-one (837) (5.2 g, 40.8%) as a colorless oil. cooled to room temperature extracted with ethyl acetate (2×25 mL) dried over sodium sulfate filtered concentrated in vacuo The residue was purified by chromatography (0-20% EtOAc in hexanes)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-fluorophenol (8.0 g, 71.4 mmol) in dimethylformamide (130.0 mL) was added potassium carbonate (13.5 g, 97.4 mmol) and 2-bromopentan-3-one (836) (10.7 g, 64.9 mmol). The suspension was heated at 70° C. for 18 h, cooled to room temperature, diluted with water (50 mL), and extracted with ethyl acetate (2×25 mL). The organic layers were combined, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by chromatography (0-20% EtOAc in hexanes) to provide the desired 2-(4-fluorophenoxy)pentan-3-one (837) (5.2 g, 40.8%) as a colorless oil. cooled to room temperature extracted with ethyl acetate (2×25 mL) dried over sodium sulfate filtered concentrated in vacuo The residue was purified by chromatography (0-20% EtOAc in hexanes)

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

Procedure: The solution of tert-butyl 2-methyl-1H-pyrrolo[2,3-b]pyridine-3-carboxylate (1.0 g, 4.31 mmol), 2-bromopentan-3-one (1.1 g, 6.46 mmol), Cs2CO3 (2.8 g, 8.61 mmol), KI (142.9 mg, 0.86 mmol) in CH3CN (4 ml) were stirred at 70° C. for 2 h. After the reaction completed, the solution was cooled to r.t. and filtered off. The filtration was evaporated under vacuum. The residue was purified by flash column (Eluent: PE:EtOAc=5:1) to get tert-butyl 2-methyl-1-(3-oxopentan-2-yl)-1H-pyrrolo[2,3-b]pyridine-3-carboxylate as a white oil. (100 mg yield 7%) filtered off The filtration was evaporated under vacuum The residue was purified by flash column (Eluent: PE:EtOAc=5:1)

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

Procedure: To a stirred solution of N-(5-iodopyridin-2-yl)-4-methylbenzenesulfonamide (3 g) and 2-bromopentan-3-one (3.3 g) in THF (50 ml) was added N,N-diisopropylethylamine (5.6 ml) at 0° C., and the resulting mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated in vacuo, poured into saturated NaHCO3 solution and extracted with EtOAc. The extract was washed with brine, dried over Na2SO4, concentrated in vacuo and purified by silica gel column chromatography (hexane/EtOAc) to afford the title compound (1.6 g) as a yellow solid. The reaction mixture was concentrated in vacuo poured into saturated NaHCO3 solution extracted with EtOAc The extract was washed with brine dried over Na2SO4 concentrated in vacuo purified by silica gel column chromatography (hexane/EtOAc)

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

Procedure: To a stirred solution of N-(5-iodopyridin-2-yl)-4-methylbenzenesulfonamide (3 g) and 2-bromopentan-3-one (3.3 g) in THF (50 ml) was added N,N-diisopropylethylamine (5.6 ml) at 0° C., and the resulting mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated in vacuo, poured into saturated NaHCO3 solution and extracted with EtOAc. The extract was washed with brine, dried over Na2SO4, concentrated in vacuo and purified by silica gel column chromatography (hexane/EtOAc) to afford the title compound (1.6 g) as a yellow solid. The reaction mixture was concentrated in vacuo poured into saturated NaHCO3 solution extracted with EtOAc The extract was washed with brine dried over Na2SO4 concentrated in vacuo purified by silica gel column chromatography (hexane/EtOAc)

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

Procedure: To a stirred mixture of 2-bromopentan-3-one (2.0 g), 2-amino-5-iodopyridine (1.0 g) and EtOH (50 ml) was heated at reflux for 16 h. The reaction mixture was cooled and concentrated in vacuo. The residue was diluted with water (100 ml), and extracted with DCM. The DCM layer was washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc) to give the title compound (400 mg) as a yellow solid. was heated at reflux for 16 h The reaction mixture was cooled concentrated in vacuo The residue was diluted with water (100 ml) extracted with DCM The DCM layer was washed with brine dried over Na2SO4 concentrated in vacuo The residue was purified by silica gel column chromatography (hexane/EtOAc)