1-benzofuran-3-carbonyl chloride

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into solutions of 154 (5.0 mmol) in 200 mL of dry toluene were added triethylamine (4 mL) and 2-amino-4,5-methylenedioxy acetophenone (148) (5 mmol). The mixtures were stirred at 20±2° C. for 24 h and then evaporated. The residues were washed with acetone and EtOH and then recrystallized from acetone or EtOH to form 155. Obtained as a pale-yellow solid; mp 144-145° C.; ESI-MS (Positive mode): m/z 324 [M+H]+; 1H-NMR (400 MHz, DMSO-d6): δ 2.63 (3H, s), 6.19 (2H, s), 7.41-7.50 (21-1, m), 7.68 (1H, s), 7.75 (1H, dd, J=1.6, 6.8 Hz), 8.15 (1H, dd, J=2.0, 8.8 Hz), 8.27 (1H, s), 8.71 (1H, s), 12.63 (1H, s); IR (KBr): 1635, 1677 (C═O) cm−1. evaporated The residues were washed with acetone and EtOH recrystallized from acetone or EtOH

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

Procedure: The synthetic procedure of target compounds 158 is illustrated in Scheme 12. The starting 2-amino-4,5-methylenedioxy acetophenone (148) was first reacted with benzo[b]furan-3-carbonyl chloride (154) to give N-(6-Acetyl-1,3-benzodioxol-5-yl)-1-benzofuran-3-carboxamide (155). Then, the intermediates (155) was subjected to cyclization in dioxane, in the presence of NaOH, to afford 2-(3-Benzo[b]furyl)-6,7-methylenedioxyquinolin-4-one (156). Compound 156 was first reacted with tetrabenzylpyrophosphate in THF, in the presence of NaH, to yield dibenzyl 2-(3-benzo[b]furyl)-6,7-methylenedioxyquinolin-4-yl phosphate (157). Compound 157 was then subjected to catalytic hydrogenation in MeOH to give its diphosphoric acid (158).

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

Procedure: Benzofuran-3-carboxylic acid (1.00 g, 6.17 mmol) was suspended in methylene chloride (20 mL), and oxalyl chloride (1.08 mL, 12.34 mmol) was added dropwise. To this reaction liquor, a catalytic amount of DMF (one drop) was added, and the reaction liquor was stirred for one hour at room temperature. The solvent was distilled off under reduced pressure, to obtain benzofuran-3-carboxylic acid chloride as a solid. The obtained acid chloride was suspended in 1,2-dichloroethane (20 mL), and (4-amino-3-chlorophenyl)acetic acid ethyl ester hydrochloride (1.54 g, 6.17 mmol) was added. The mixture was heated and stirred for 20 hours. The mixture was left to cool naturally to room temperature, and then the solvent was distilled off under reduced pressure. The obtained residue was purified by flash column chromatography (Flash Chromatography System from Biotage AB, column size: 40S, elution solvent: n-hexane:ethyl acetate=95:5 to 75:25), to obtain the title compound (2.08 g, 94%) as a solid. The solvent was distilled off under reduced pressure

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into solutions of 154 (5.0 mmol) in 200 mL of dry toluene were added triethylamine (4 mL) and 2-amino-4,5-methylenedioxy acetophenone (148) (5 mmol). The mixtures were stirred at 20±2° C. for 24 h and then evaporated. The residues were washed with acetone and EtOH and then recrystallized from acetone or EtOH to form 155. Obtained as a pale-yellow solid; mp 144-145° C.; ESI-MS (Positive mode): m/z 324 [M+H]+; 1H-NMR (400 MHz, DMSO-d6): δ 2.63 (3H, s), 6.19 (2H, s), 7.41-7.50 (21-1, m), 7.68 (1H, s), 7.75 (1H, dd, J=1.6, 6.8 Hz), 8.15 (1H, dd, J=2.0, 8.8 Hz), 8.27 (1H, s), 8.71 (1H, s), 12.63 (1H, s); IR (KBr): 1635, 1677 (C═O) cm−1. evaporated The residues were washed with acetone and EtOH recrystallized from acetone or EtOH

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

Procedure: The synthetic procedure of target compounds 158 is illustrated in Scheme 12. The starting 2-amino-4,5-methylenedioxy acetophenone (148) was first reacted with benzo[b]furan-3-carbonyl chloride (154) to give N-(6-Acetyl-1,3-benzodioxol-5-yl)-1-benzofuran-3-carboxamide (155). Then, the intermediates (155) was subjected to cyclization in dioxane, in the presence of NaOH, to afford 2-(3-Benzo[b]furyl)-6,7-methylenedioxyquinolin-4-one (156). Compound 156 was first reacted with tetrabenzylpyrophosphate in THF, in the presence of NaH, to yield dibenzyl 2-(3-benzo[b]furyl)-6,7-methylenedioxyquinolin-4-yl phosphate (157). Compound 157 was then subjected to catalytic hydrogenation in MeOH to give its diphosphoric acid (158).

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into solutions of 154 (5.0 mmol) in 200 mL of dry toluene were added triethylamine (4 mL) and 2-amino-4,5-methylenedioxy acetophenone (148) (5 mmol). The mixtures were stirred at 20±2° C. for 24 h and then evaporated. The residues were washed with acetone and EtOH and then recrystallized from acetone or EtOH to form 155. Obtained as a pale-yellow solid; mp 144-145° C.; ESI-MS (Positive mode): m/z 324 [M+H]+; 1H-NMR (400 MHz, DMSO-d6): δ 2.63 (3H, s), 6.19 (2H, s), 7.41-7.50 (21-1, m), 7.68 (1H, s), 7.75 (1H, dd, J=1.6, 6.8 Hz), 8.15 (1H, dd, J=2.0, 8.8 Hz), 8.27 (1H, s), 8.71 (1H, s), 12.63 (1H, s); IR (KBr): 1635, 1677 (C═O) cm−1. evaporated The residues were washed with acetone and EtOH recrystallized from acetone or EtOH

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

Procedure: The synthetic procedure of target compounds 158 is illustrated in Scheme 12. The starting 2-amino-4,5-methylenedioxy acetophenone (148) was first reacted with benzo[b]furan-3-carbonyl chloride (154) to give N-(6-Acetyl-1,3-benzodioxol-5-yl)-1-benzofuran-3-carboxamide (155). Then, the intermediates (155) was subjected to cyclization in dioxane, in the presence of NaOH, to afford 2-(3-Benzo[b]furyl)-6,7-methylenedioxyquinolin-4-one (156). Compound 156 was first reacted with tetrabenzylpyrophosphate in THF, in the presence of NaH, to yield dibenzyl 2-(3-benzo[b]furyl)-6,7-methylenedioxyquinolin-4-yl phosphate (157). Compound 157 was then subjected to catalytic hydrogenation in MeOH to give its diphosphoric acid (158).

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

Procedure: Benzofuran-3-carboxylic acid (1.00 g, 6.17 mmol) was suspended in methylene chloride (20 mL), and oxalyl chloride (1.08 mL, 12.34 mmol) was added dropwise. To this reaction liquor, a catalytic amount of DMF (one drop) was added, and the reaction liquor was stirred for one hour at room temperature. The solvent was distilled off under reduced pressure, to obtain benzofuran-3-carboxylic acid chloride as a solid. The obtained acid chloride was suspended in 1,2-dichloroethane (20 mL), and (4-amino-3-chlorophenyl)acetic acid ethyl ester hydrochloride (1.54 g, 6.17 mmol) was added. The mixture was heated and stirred for 20 hours. The mixture was left to cool naturally to room temperature, and then the solvent was distilled off under reduced pressure. The obtained residue was purified by flash column chromatography (Flash Chromatography System from Biotage AB, column size: 40S, elution solvent: n-hexane:ethyl acetate=95:5 to 75:25), to obtain the title compound (2.08 g, 94%) as a solid. The solvent was distilled off under reduced pressure