methyl 4-(furan-2-yl)-2,4-dioxobutanoate

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

Procedure: (see, e.g., Volochnyuk, D. M., et al., J Comb Chem 2010, 12, 510-7). A solution of 22 (306 mg, 1.47 mmol) and 20 (295 mg, 1.50 mmol) in glacial AcOH (10 mL) was heated to reflux for 3 h. When the reaction mixture was cooled down to room temperature, yellow precipitates formed which were filtered and washed with H2O. Filtercake was placed in a vacuum oven to give the title compound (470 mg, 87%) as a yellow solid. 1H NMR (500 MHz, CDCl3) δ 8.48 (s, 1H), 8.29 (d, J=9.1 Hz, 1H), 8.06 (s, 1H), 7.62 (s, 1H), 7.43 (t, J=8.1 Hz, 1H), 7.28-7.23 (m, 2H), 6.63-6.59 (m, 1H), 4.06 (s, 3H), 2.75 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 165.53, 152.95, 151.82, 148.42, 144.43, 143.32, 140.31, 134.59, 133.91, 129.93, 125.41, 120.77, 118.52, 113.87, 112.57, 112.24, 110.94, 52.73, 16.21. to reflux for 3 h yellow precipitates formed which were filtered washed with H2O

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

Procedure: (see, e.g., Volochnyuk, D. M., et al., J Comb Chem 2010, 12, 510-7). A solution of 22 (306 mg, 1.47 mmol) and 20 (295 mg, 1.50 mmol) in glacial AcOH (10 mL) was heated to reflux for 3 h. When the reaction mixture was cooled down to room temperature, yellow precipitates formed which were filtered and washed with H2O. Filtercake was placed in a vacuum oven to give the title compound (470 mg, 87%) as a yellow solid. 1H NMR (500 MHz, CDCl3) δ 8.48 (s, 1H), 8.29 (d, J=9.1 Hz, 1H), 8.06 (s, 1H), 7.62 (s, 1H), 7.43 (t, J=8.1 Hz, 1H), 7.28-7.23 (m, 2H), 6.63-6.59 (m, 1H), 4.06 (s, 3H), 2.75 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 165.53, 152.95, 151.82, 148.42, 144.43, 143.32, 140.31, 134.59, 133.91, 129.93, 125.41, 120.77, 118.52, 113.87, 112.57, 112.24, 110.94, 52.73, 16.21. to reflux for 3 h yellow precipitates formed which were filtered washed with H2O

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

Procedure: (see, e.g., Ghosh, A. K., et al., J Med Chem 2005, 48, 6767-71). To a stirred solution of MeOH (150 mL) at room temperature under nitrogen, freshly cut Na (1.81 g, 78.7 mmol) was added in pieces and with care. After all the sodium dissolved, a mixture of 2-acetylfuran (6 mL, 59.8 mmol) and diethyl oxalate (8.14 mL, 59.9 mmol) was added dropwise over a period of 3 min at room temperature. The resulting mixture was continued to stir. Brown precipitates formed after 20 min stir. The mixture was stirred for a total of 1 h. The reaction mixture was cooled to 0° C., and a mixture of concentrated H2SO4 and ice was added. Some solid precipitated at this point which was filtered off but was not the desired product by 1H NMR. The filterate was extracted with CH2Cl2 (50 mL×2). The combined organic layers were washed with brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude was recrystallized from hot iPrOH to give the title compound (4.15 g, 35%) as a dark brown solid. 1H NMR (400 MHz, CDCl3) δ 7.67-7.65 (m, 1H), 7.33 (d, J=3.6 Hz, 1H), 6.93 (s, 1H), 6.60 (dd, J=3.5, 1.5 Hz, 1H), 3.91 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 181.01, 165.39, 162.43, 150.82, 147.73, 118.58, 113.14, 99.17, 53.18. was added dropwise over a period of 3 min at room temperature Brown precipitates formed after 20 min stir The mixture was stirred for a total of 1 h was added Some solid precipitated at this point which was filtered off The filterate was extracted with CH2Cl2 (50 mL×2) The combined organic layers were washed with brine dried (Na2SO4) filtered concentrated under reduced pressure The crude was recrystallized from hot iPrOH

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

Procedure: A stirred solution compound 5 (10.0 g, 50 mmol) and (2-chlorophenyl)hydrazine hydrochloride (10.0 g, 56 mmol) in methanol 80 mL was heated to reflux for 6 h. On cooling to 0° C., solid crashed out, filtered and washed with cold methanol to afford the title compound 6 (12.0 g, 80.0%) which was used for further reaction. to reflux for 6 h filtered washed with cold methanol

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

Procedure: (see, e.g., Volochnyuk, D. M., et al., J Comb Chem 2010, 12, 510-7). A solution of 22 (306 mg, 1.47 mmol) and 20 (295 mg, 1.50 mmol) in glacial AcOH (10 mL) was heated to reflux for 3 h. When the reaction mixture was cooled down to room temperature, yellow precipitates formed which were filtered and washed with H2O. Filtercake was placed in a vacuum oven to give the title compound (470 mg, 87%) as a yellow solid. 1H NMR (500 MHz, CDCl3) δ 8.48 (s, 1H), 8.29 (d, J=9.1 Hz, 1H), 8.06 (s, 1H), 7.62 (s, 1H), 7.43 (t, J=8.1 Hz, 1H), 7.28-7.23 (m, 2H), 6.63-6.59 (m, 1H), 4.06 (s, 3H), 2.75 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 165.53, 152.95, 151.82, 148.42, 144.43, 143.32, 140.31, 134.59, 133.91, 129.93, 125.41, 120.77, 118.52, 113.87, 112.57, 112.24, 110.94, 52.73, 16.21. to reflux for 3 h yellow precipitates formed which were filtered washed with H2O

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

Procedure: (see, e.g., Ghosh, A. K., et al., J Med Chem 2005, 48, 6767-71). To a stirred solution of MeOH (150 mL) at room temperature under nitrogen, freshly cut Na (1.81 g, 78.7 mmol) was added in pieces and with care. After all the sodium dissolved, a mixture of 2-acetylfuran (6 mL, 59.8 mmol) and diethyl oxalate (8.14 mL, 59.9 mmol) was added dropwise over a period of 3 min at room temperature. The resulting mixture was continued to stir. Brown precipitates formed after 20 min stir. The mixture was stirred for a total of 1 h. The reaction mixture was cooled to 0° C., and a mixture of concentrated H2SO4 and ice was added. Some solid precipitated at this point which was filtered off but was not the desired product by 1H NMR. The filterate was extracted with CH2Cl2 (50 mL×2). The combined organic layers were washed with brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude was recrystallized from hot iPrOH to give the title compound (4.15 g, 35%) as a dark brown solid. 1H NMR (400 MHz, CDCl3) δ 7.67-7.65 (m, 1H), 7.33 (d, J=3.6 Hz, 1H), 6.93 (s, 1H), 6.60 (dd, J=3.5, 1.5 Hz, 1H), 3.91 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 181.01, 165.39, 162.43, 150.82, 147.73, 118.58, 113.14, 99.17, 53.18. was added dropwise over a period of 3 min at room temperature Brown precipitates formed after 20 min stir The mixture was stirred for a total of 1 h was added Some solid precipitated at this point which was filtered off The filterate was extracted with CH2Cl2 (50 mL×2) The combined organic layers were washed with brine dried (Na2SO4) filtered concentrated under reduced pressure The crude was recrystallized from hot iPrOH

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

Procedure: A stirred solution compound 5 (10.0 g, 50 mmol) and (2-chlorophenyl)hydrazine hydrochloride (10.0 g, 56 mmol) in methanol 80 mL was heated to reflux for 6 h. On cooling to 0° C., solid crashed out, filtered and washed with cold methanol to afford the title compound 6 (12.0 g, 80.0%) which was used for further reaction. to reflux for 6 h filtered washed with cold methanol