5-ethylfuran-2-carbaldehyde

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

Procedure: The title compound, MS m/e (%): 309 (M++2, 100), was prepared in accordance with the general method of example 63 from 4-bromo-pyridine-2,6-diamine, O-mesitylene-sulfonylhydroxylamine, and 5-ethyl-2-furaldehyde. The purification was performed with reversed phase HPLC eluting with an acetonitrile/water gradient.

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

Procedure: The title compound, MS m/e (%): 309 (M++2, 100), was prepared in accordance with the general method of example 63 from 4-bromo-pyridine-2,6-diamine, O-mesitylene-sulfonylhydroxylamine, and 5-ethyl-2-furaldehyde. The purification was performed with reversed phase HPLC eluting with an acetonitrile/water gradient.

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

Procedure: To a freshly prepared solution of LDA (15 mmol) in 30 mL of THF cooled to -78° C. was added a solution of 3,4-methylenedioxybenzenebutanoic acid, methyl ester (14 mmol), from step 558 above, in 10 mL of THF. The solution was stirred for 5 minutes, and a solution of 5-ethylfuran-2-carboxaldehyde (13.8 mmol), from step 55b above, in 30 mL of THF was added. The reaction mixture was warmed to 0° C., and the reaction was quenched with 10 mL of satd NH4Cl. The organic layer was separated, and the aqueous layer was extracted with ether. The organic layers were combined, dried and concentrated. The residue was dissolved in 50 mL of methylene chloride, and the solution was cooled to 0° C. To this solution was added a solution of SnCl4 (1M, 13 mmol) in methylene chloride, and the reaction mixtrue was stirred for 5 minutes. The reaction was quenched with 1 N HCl (10 mL). The organic layer was separated, and the aqueous layer was extracted with methylene chloride. The organic layers were combined, dried, filtered and concentrated. The crude methyl ester intermediate was hydrolyzed with KOH in methanol by standard procedures, and the title product was isolated (3.04 g). NMR (CDCl3) δ:6.56 (s, 1H), 6.54 (s, 1H), 5.91-5.81 (m, 4H), 4.39 (d, J=7 Hz, 1H), 3.13 (m, 1H), 2.80 (t, J=7 Hz, 2H), 2.59 (q, J=8 Hz, 2H), 2.18-1.96 (m, 2H), 1.20 (t, J=8 Hz, 3H). the reaction was quenched with 10 mL of satd NH4Cl The organic layer was separated the aqueous layer was extracted with ether dried concentrated The residue was dissolved in 50 mL of methylene chloride the solution was cooled to 0° C the reaction mixtrue was stirred for 5 minutes The reaction was quenched with 1 N HCl (10 mL) The organic layer was separated the aqueous layer was extracted with methylene chloride dried filtered concentrated

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

Procedure: A sample of DMF (9.3 mL, 120 mmol) was cooled to 0° C. and POCl3 (3.37 g, 22 mmol) was added, the mixture was stirred for 1 hour at 0° C., then 2-ethyl furan (1.92 g, 20 mmol) was added. The reaction was quenched by pouring onto ice, and the mixture was stirred for 18 hours. The mixture was extracted with hexane, which was dried over MgSO4 and concentrated to give 1.71 g of the title compound (used without further purification). The reaction was quenched by pouring onto ice the mixture was stirred for 18 hours The mixture was extracted with hexane, which was dried over MgSO4 concentrated

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

Procedure: The title compound, MS m/e (%): 309 (M++2, 100), was prepared in accordance with the general method of example 63 from 4-bromo-pyridine-2,6-diamine, O-mesitylene-sulfonylhydroxylamine, and 5-ethyl-2-furaldehyde. The purification was performed with reversed phase HPLC eluting with an acetonitrile/water gradient.

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

Procedure: The title compound, MS m/e (%): 309 (M++2, 100), was prepared in accordance with the general method of example 63 from 4-bromo-pyridine-2,6-diamine, O-mesitylene-sulfonylhydroxylamine, and 5-ethyl-2-furaldehyde. The purification was performed with reversed phase HPLC eluting with an acetonitrile/water gradient.

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

Procedure: To a freshly prepared solution of LDA (15 mmol) in 30 mL of THF cooled to -78° C. was added a solution of 3,4-methylenedioxybenzenebutanoic acid, methyl ester (14 mmol), from step 558 above, in 10 mL of THF. The solution was stirred for 5 minutes, and a solution of 5-ethylfuran-2-carboxaldehyde (13.8 mmol), from step 55b above, in 30 mL of THF was added. The reaction mixture was warmed to 0° C., and the reaction was quenched with 10 mL of satd NH4Cl. The organic layer was separated, and the aqueous layer was extracted with ether. The organic layers were combined, dried and concentrated. The residue was dissolved in 50 mL of methylene chloride, and the solution was cooled to 0° C. To this solution was added a solution of SnCl4 (1M, 13 mmol) in methylene chloride, and the reaction mixtrue was stirred for 5 minutes. The reaction was quenched with 1 N HCl (10 mL). The organic layer was separated, and the aqueous layer was extracted with methylene chloride. The organic layers were combined, dried, filtered and concentrated. The crude methyl ester intermediate was hydrolyzed with KOH in methanol by standard procedures, and the title product was isolated (3.04 g). NMR (CDCl3) δ:6.56 (s, 1H), 6.54 (s, 1H), 5.91-5.81 (m, 4H), 4.39 (d, J=7 Hz, 1H), 3.13 (m, 1H), 2.80 (t, J=7 Hz, 2H), 2.59 (q, J=8 Hz, 2H), 2.18-1.96 (m, 2H), 1.20 (t, J=8 Hz, 3H). the reaction was quenched with 10 mL of satd NH4Cl The organic layer was separated the aqueous layer was extracted with ether dried concentrated The residue was dissolved in 50 mL of methylene chloride the solution was cooled to 0° C the reaction mixtrue was stirred for 5 minutes The reaction was quenched with 1 N HCl (10 mL) The organic layer was separated the aqueous layer was extracted with methylene chloride dried filtered concentrated

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

Procedure: A sample of DMF (9.3 mL, 120 mmol) was cooled to 0° C. and POCl3 (3.37 g, 22 mmol) was added, the mixture was stirred for 1 hour at 0° C., then 2-ethyl furan (1.92 g, 20 mmol) was added. The reaction was quenched by pouring onto ice, and the mixture was stirred for 18 hours. The mixture was extracted with hexane, which was dried over MgSO4 and concentrated to give 1.71 g of the title compound (used without further purification). The reaction was quenched by pouring onto ice the mixture was stirred for 18 hours The mixture was extracted with hexane, which was dried over MgSO4 concentrated

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

Procedure: To a solution of 4-hydroxy-benzoic acid hydrazide (0.3 g, 0.002 mol) and 5-ethyl-2-furaldehyde (0.25 g, 0.002 mol) in abs. EtOH (10 mL), was added 1 drop of acetic acid. The reaction mixture was refluxed for 5 hours. The reaction mixture was cooling to room temperature and concentrated to remove solvent. The resulting residue was solidified by pet ether to give red solid 0.44 g, in 85% yield, mp: 60.5° C. 1H NMR (DMSO-d6) δ 11.53 (s, 1H), 10.16 (s, 1H), 8.24 (s, 1H), 7.79 (d, 2H), 6.87 (d, 2H), 6.81 (s, 1H), 2.71 (q, 2H), 1.24 (t, 3H). 13C NMR (DMSO-d6) δ 164.5, 162.1, 161.2, 149.8, 138.5, 131.5, 125.7, 116.9, 116.7, 108.9, 22.8, 13.8. Anal. Calcd for C14H14N2O3: C, 65.11; H, 5.46; N, 10.85. Found: C, 65.00; H, 5.36; N, 10.55. The reaction mixture was refluxed for 5 hours concentrated to remove solvent

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

Procedure: To a solution of 4-hydroxy-benzoic acid hydrazide (0.3 g, 0.002 mol) and 5-ethyl-2-furaldehyde (0.25 g, 0.002 mol) in abs. EtOH (10 mL), was added 1 drop of acetic acid. The reaction mixture was refluxed for 5 hours. The reaction mixture was cooling to room temperature and concentrated to remove solvent. The resulting residue was solidified by pet ether to give red solid 0.44 g, in 85% yield, mp: 60.5° C. 1H NMR (DMSO-d6) δ 11.53 (s, 1H), 10.16 (s, 1H), 8.24 (s, 1H), 7.79 (d, 2H), 6.87 (d, 2H), 6.81 (s, 1H), 2.71 (q, 2H), 1.24 (t, 3H). 13C NMR (DMSO-d6) δ164.5, 162.1, 161.2, 149.8, 138.5, 131.5, 125.7, 116.9, 116.7, 108.9, 22.8, 13.8. Anal. Calcd for C14H14N2O3: C, 65.11; H, 5.46; N, 10.85. Found: C, 65.00; H, 5.36; N, 10.55. The reaction mixture was refluxed for 5 hours concentrated to remove solvent

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

Procedure: To a suspension of tBuOK (61.4 g, 0.54 mol) in tBuOH (180 mL) was added a suspension of 5-ethyl-2-furaldehyde (22.5 g, 0.18 mol) in succinic acid diethyl ester (142.1 g, 0.82 mol). The reaction mixture was refluxed for 1 h. Then the same amounts of tBuOK, tBuOH and succinic acid diethyl ester were added at the same temperature, and the reaction mixture was stirred at reflux for another 1 h. TLC (petroleum ether/EtOAc 2:1) indicated the complete consumption of the furaldehyde. The reaction mixture was allowed to cool to room temperature, acidified to a pH˜2 by 20% aqueous HCl (200 mL) and extracted with EtOAc (500 mL×3). The organic phase was washed with 10% aqueous Na2CO3 (500 mL×3). The combined aqueous layers was washed with ethyl ether (500 mL) and acidified to a pH˜2 with 20% aqueous HCl (100 mL). The aqueous phase was finally extracted with EtOAc (500 mL×4). The combined organic layers were dried over Na2SO4 and concentrated to give the crude acid (45.4 g, 100%), which was directly used to next step without further purification. was added The reaction mixture was refluxed for 1 h at reflux for another 1 h the complete consumption of the furaldehyde extracted with EtOAc (500 mL×3) The organic phase was washed with 10% aqueous Na2CO3 (500 mL×3) The combined aqueous layers was washed with ethyl ether (500 mL) The aqueous phase was finally extracted with EtOAc (500 mL×4) The combined organic layers were dried over Na2SO4 concentrated

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

Procedure: To a solution of 4-hydroxy-benzoic acid hydrazide (0.3 g, 0.002 mol) and 5-ethyl-2-furaldehyde (0.25 g, 0.002 mol) in abs. EtOH (10 mL), was added 1 drop of acetic acid. The reaction mixture was refluxed for 5 hours. The reaction mixture was cooling to room temperature and concentrated to remove solvent. The resulting residue was solidified by pet ether to give red solid 0.44 g, in 85% yield, mp: 60.5° C. 1H NMR (DMSO-d6) δ 11.53 (s, 1H), 10.16 (s, 1H), 8.24 (s, 1H), 7.79 (d, 2H), 6.87 (d, 2H), 6.81 (s, 1H), 2.71 (q, 2H), 1.24 (t, 3H). 13C NMR (DMSO-d6) δ 164.5, 162.1, 161.2, 149.8, 138.5, 131.5, 125.7, 116.9, 116.7, 108.9, 22.8, 13.8. Anal. Calcd for C14H14N2O3: C, 65.11; H, 5.46; N, 10.85. Found: C, 65.00; H, 5.36; N, 10.55. The reaction mixture was refluxed for 5 hours concentrated to remove solvent