N-methoxy-N-methylfuran-3-carboxamide

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

Procedure: A solution of N-methoxy-N-methylfuran-3-carboxamide (913 mg, 5.89 mmol) in anhydrous THF (10 mL) was cooled to −78° C. under nitrogen, and a solution of benzylmagnesium chloride in THF (2 mol/L, 3.53 mL) was added through a syringe. The reaction mixture was stirred at this temperature for 5 hours. TLC (PE:EtOAc=5:1) indicated reaction was nearly complete, saturated NH4Cl solution (20 mL) was added to quench the reaction, and the aqueous layer was extracted with EtOAc (80 mL). The organic layer was washed with brine (30 mL), dried over Na2SO4, filtered, and concentrated to afford 1-(furan-3-yl)-2-phenylethanone as a yellow oil (696 mg, yield: 63.2%). reaction to quench the reaction the aqueous layer was extracted with EtOAc (80 mL) The organic layer was washed with brine (30 mL) dried over Na2SO4 filtered concentrated

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

Procedure: The title compound was prepared from furan-3-carboxylic acid (3.4 g, 0.030 mol), N,O-dimethylhydroxylamine hydrochloride hydrochloride (2.9 g, 0.030 mol) triethylamine (8.3 mL, 0.060 mol) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorphosphate (13.3 g, 0.030 mol) according to the general procedure described in Example 1 for N-(3-pyridylmethyl)-5-chloro-3-phenylthio-2-carboxamide. NMR (DMSO-d6) δ8.25 (1H, s), 7.75 (1H, s), 3.70 (3H, s), 3.22 (3H, s).

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

Procedure: The title compound was prepared from furan-3-carboxylic acid (3.4 g, 0.030 mol), N,O-dimethylhydroxylamine hydrochloride hydrochloride (2.9 g, 0.030 mol) triethylamine (8.3 mL, 0.060 mol) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorphosphate (13.3 g, 0.030 mol) according to the general procedure described in Example 1 for N-(3-pyridylmethyl)-5-chloro-3-phenylthio-2-carboxamide. NMR (DMSO-d6) δ8.25 (1H, s), 7.75 (1H, s), 3.70 (3H, s), 3.22 (3H, s).

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

Procedure: A solution of N-methoxy-N-methylfuran-3-carboxamide (913 mg, 5.89 mmol) in anhydrous THF (10 mL) was cooled to −78° C. under nitrogen, and a solution of benzylmagnesium chloride in THF (2 mol/L, 3.53 mL) was added through a syringe. The reaction mixture was stirred at this temperature for 5 hours. TLC (PE:EtOAc=5:1) indicated reaction was nearly complete, saturated NH4Cl solution (20 mL) was added to quench the reaction, and the aqueous layer was extracted with EtOAc (80 mL). The organic layer was washed with brine (30 mL), dried over Na2SO4, filtered, and concentrated to afford 1-(furan-3-yl)-2-phenylethanone as a yellow oil (696 mg, yield: 63.2%). reaction to quench the reaction the aqueous layer was extracted with EtOAc (80 mL) The organic layer was washed with brine (30 mL) dried over Na2SO4 filtered concentrated

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

Procedure: To a solution of 3-(N-methyl-N-methoxycarbamoyl)furan (14 g, 0.09 mol) in 150 ml of THF cooled to -78° C. was added in portions 36.1 ml (0.108 mol) of 3M methylmagnesium bromide in ether and the mixture was allowed to warm to room temperature, and then stirred for 30 min. To the above mixture was added a cold 2N HCl (100 ml) and the aqueous layer was extracted with ether (3×100 ml), the combined organic layer was washed with brine, dried over sodium sulfate, and concentrated in vacuo to yield a pale-yellow oil. The above oil was chromatographed on silica (methylene chloride/hexane 2:1) to afford 6.95 g (70.2%) of 1-(3-furyl)-1-propanone as a colorless oil which crystallized as a white solid. the aqueous layer was extracted with ether (3×100 ml) the combined organic layer was washed with brine dried over sodium sulfate concentrated in vacuo to yield a pale-yellow oil The above oil was chromatographed on silica (methylene chloride/hexane 2:1)

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

Procedure: To a solution of furan-3-carboxylic acid (26 g, 0.23 mol) in 250 ml of toluene was added 24.15 ml (0.276 mol) of oxalyl chloride and 1 drop of pyridine and the mixture was heated on a steam-bath for 2 h. The mixture was cooled to room temperature, N,O-dimethylhydroxamine hydrochloride (24.66 g, 0.253 mol), 4-dimethylaminopyridine (DMAP, 1.2 g, 0.01 mol), and 600 ml of methylene chloride were added. The mixture was cooled to 0° C., 50.1 ml of pyridine in 50 ml of methylene chloride was added slowly, the mixture was allowed to warm to room temperature (3 h), and 2 g of N,O-dimethylhydroxamine hydrochloride and 1 g of 4-dimethylaminopyridine (DMAP) were added. The resulting mixture was stirred for 12 h. The above mixture was cooled to 0° C., filtered, and the filtrate was washed with 3N HCl, brine, dried over sodium sulfate, and concentrated in vacuo to yield 14 g (39%) of 3-(N-methyl-N-methoxycarbamoyl)furan. the mixture was heated on a steam-bath for 2 h The mixture was cooled to 0° C. were added The above mixture was cooled to 0° C. filtered the filtrate was washed with 3N HCl, brine dried over sodium sulfate concentrated in vacuo

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of n-butyllithium (2.5M, 28 ml, 0.07 mol) in 150 ml of ether at -78° C. was added a solution of 3-bromofuran (10 g, 0.0628 mol) in 30 ml of ether over a 20 min period and the mixture was stirred at -78° C. for 20 min. To the above mixture was added 3-(N-methyl-N-methoxycarbamoyl)furan (9.16 g, 0.059 mol) in 30 ml of ether over a 15 min period and the mixture was stirred at room temperature for 1/2 h. The reaction mixture was quenched with 200 ml of ammonium chloride solution, 500 ml of methylene chloride was added and the mixture was stirred. The organic layer was dried over sodium sulfate, concentrated in vacuo, and the residue was triturated in 100 ml of hexane/t-butylmethylether (9:1). The solid product was filtered and washed with t-butylmethylether to afford 7.5 g (78.3%) of di-(3-furyl)ketone. the mixture was stirred at room temperature for 1/2 h The reaction mixture was quenched with 200 ml of ammonium chloride solution, 500 ml of methylene chloride was added the mixture was stirred The organic layer was dried over sodium sulfate concentrated in vacuo the residue was triturated in 100 ml of hexane/t-butylmethylether (9:1) The solid product was filtered washed with t-butylmethylether

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of n-butyllithium (2.5M, 28 ml, 0.07 mol) in 150 ml of ether at -78° C. was added a solution of 3-bromofuran (10 g, 0.0628 mol) in 30 ml of ether over a 20 min period and the mixture was stirred at -78° C. for 20 min. To the above mixture was added 3-(N-methyl-N-methoxycarbamoyl)furan (9.16 g, 0.059 mol) in 30 ml of ether over a 15 min period and the mixture was stirred at room temperature for 1/2 h. The reaction mixture was quenched with 200 ml of ammonium chloride solution, 500 ml of methylene chloride was added and the mixture was stirred. The organic layer was dried over sodium sulfate, concentrated in vacuo, and the residue was triturated in 100 ml of hexane/t-butylmethylether (9:1). The solid product was filtered and washed with t-butylmethylether to afford 7.5 g (78.3%) of di-(3-furyl)ketone. the mixture was stirred at room temperature for 1/2 h The reaction mixture was quenched with 200 ml of ammonium chloride solution, 500 ml of methylene chloride was added the mixture was stirred The organic layer was dried over sodium sulfate concentrated in vacuo the residue was triturated in 100 ml of hexane/t-butylmethylether (9:1) The solid product was filtered washed with t-butylmethylether

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

Procedure: To a suspension of furan-3-carboxylic acid (36 g, 0.32 mol) in 250 ml of toluene was added 49 g (0.385 mol) of oxalyl chloride and 1 drop of pyridine, and the mixture was heated at 80°-90° C. for 1.5 h. The mixture was cooled to room temperature, N,O-dimethylhydroxylamine hydrochloride (35 g, 0.36 mol), 4-dimethylaminopyridine (DMAP, 1.8 g, 0.0147 mol), and 600 ml of methylene chloride were added. The mixture was cooled to 0° C., 68.4 g of pyridine was added slowly, the mixture was allowed to warm to room temperature and stirred for 2 h. The mixture was filtered, and the filtrate was washed with water, 5% aqueous dimethylaminopropylamine, water, 6N HCl solution, water, and brine. The organic layer was dried and concentrated in vacuo, and the residue was distilled (b.p. 85°-87° C./0.2 mm) to afford 44 g (88.7%) of 3-(N-methyl-N-methoxycarbamoyl)furan. the mixture was heated at 80°-90° C. for 1.5 h The mixture was cooled to 0° C. to warm to room temperature The mixture was filtered the filtrate was washed with water, 5% aqueous dimethylaminopropylamine, water, 6N HCl solution, water, and brine The organic layer was dried concentrated in vacuo the residue was distilled (b.p. 85°-87° C./0.2 mm)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of n-butyllithium (2.5M, 28 mL, 0.07 mol) in 150 mL of ether at -78 ° C. was added a solution of 3-bromofuran (10 g, 0.0628 mol) in 30 mL of ether over a 20 min period and the mixture was stirred at -78° C. for 20 min. To the above mixture was added 3-(N-methyl-N-methoxycarbamoyl)furan (9.16 g, 0.059 mol) in 30 mL of ether over a 15 min period and the mixture was stirred at room temperature for 1/2 h. The reaction mixture was quenched with 200 mL of ammonium chloride solution, 500 mL of methylene chloride was added and the mixture was stirred. The organic layer was dried over sodium sulfate, concentrated in vacuo, and the residue was triturated with 100 mL of hexane/TBME (9:1). The solid product was filtered and washed with TBME to afford 7.5 g (78.3%) of di-(3-furyl)ketone. the mixture was stirred at room temperature for 1/2 h The reaction mixture was quenched with 200 mL of ammonium chloride solution, 500 mL of methylene chloride was added the mixture was stirred The organic layer was dried over sodium sulfate concentrated in vacuo the residue was triturated with 100 mL of hexane/TBME (9:1) The solid product was filtered washed with TBME

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

Procedure: To a solution of furan-3-carboxylic acid (36 g, 0.32 mol) in 250 mL of toluene was added 49 mL (0.385 mol) of oxalyl chloride and 1 drop of pyridine and the mixture was heated at 80°-90° C. for 1.5 h. The mixture was cooled to room temperature, N,O-dimethylhydroxylamine hydrochloride (35 g, 0.36 mol), 4-dimethylaminopyridine (DMAP, 1.8 g, 0.0147 mol), and 600 mL of methylene chloride were added. The mixture was cooled to 0° C., 68.4 g of pyridine was added slowly, the mixture was allowed to warm to room temperature and stirred for 2 h. The mixture was filtered, and the filtrate was washed with water, 5% aqueous dimethylaminopropylamine, water, 6N HCl solution, water, and brine. The organic layer was dried and concentrated in vacuo, and the residue was distilled (b.p. 85°-87° C./0.2 mm) to afford 44 g (88.7%) of 3-(N-methyl-N-methoxycarbamoyl)furan. the mixture was heated at 80°-90° C. for 1.5 h The mixture was cooled to 0° C. to warm to room temperature The mixture was filtered the filtrate was washed with water, 5% aqueous dimethylaminopropylamine, water, 6N HCl solution, water, and brine The organic layer was dried concentrated in vacuo the residue was distilled (b.p. 85°-87° C./0.2 mm)

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

Procedure: To a solution of furan-3-carboxylic acid (36 g, 0.32 mol) in 250 mL of toluene was added 49 mL (0.385 mol) of oxalyl chloride and 1 drop of pyridine and the mixture was heated at 80°-90° C. for 1.5 h. The mixture was cooled to room temperature, N,O-dimethylhydroxylamine hydrochloride (35 g, 0.36 mol), 4-dimethylaminopyridine (DMAP, 1.8 g, 0.0147 mol), and 600 mL of methylene chloride were added. The mixture was cooled to 0° C., 68.4 g of pyridine was added slowly, the mixture was allowed to warm to room temperature and stirred for 2 h. The mixture was filtered, and the filtrate was washed with water, 5% aqueous dimethylaminopropylamine, water, 6N HCl solution, water, and brine. The organic layer was dried and concentrated in vacuo, and the residue was distilled (b.p. 85°-87° C./0.2 mm) to afford 44 g (88.7%) of 3-(N-methyl-N-methoxycarbamoyl)furan. the mixture was heated at 80°-90° C. for 1.5 h The mixture was cooled to 0° C. to warm to room temperature The mixture was filtered the filtrate was washed with water, 5% aqueous dimethylaminopropylamine, water, 6N HCl solution, water, and brine The organic layer was dried concentrated in vacuo the residue was distilled (b.p. 85°-87° C./0.2 mm)