2-(4-bromobutyl)-2-methyl-1,3-dioxolane

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of 4-nitro-2H-[1,2,3]triazole (100 mg, 0.88 mmol) and Cs2CO3 (315 mg, 0.96 mmol) in AcCN (1.0 mL) was treated with a solution of 2-(4-bromo-butyl)-2-methyl-[1,3]dioxolane (215 mg, 0.96 mmol) in AcCN (1.0 mL). The reaction mixture was stirred at 80° C. for 16 h. Water (20 mL), followed by EA (30 mL) were added. The aq. layer was extracted with EA (30 mL) and the combined org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (2:1 hept-EA) gave the title compound: TLC:rf (2:1 hept-EA)=0.33. LC-MS-conditions 02: tR=0.92 min. were added The aq. layer was extracted with EA (30 mL) extracts were dried over MgSO4 filtered the solvents were removed under reduced pressure Purification of the residue by FC (2:1 hept-EA)

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

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of 4-nitro-2H-[1,2,3]triazole (100 mg, 0.88 mmol) and Cs2CO3 (315 mg, 0.96 mmol) in AcCN (1.0 mL) was treated with a solution of 2-(4-bromo-butyl)-2-methyl-[1,3]dioxolane (215 mg, 0.96 mmol) in AcCN (1.0 mL). The reaction mixture was stirred at 80° C. for 16 h. Water (20 mL), followed by EA (30 mL) were added. The aq. layer was extracted with EA (30 mL) and the combined org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (2:1 hept-EA) gave the title compound: TLC:rf (2:1 hept-EA)=0.33. LC-MS-conditions 02: tR=0.92 min. were added The aq. layer was extracted with EA (30 mL) extracts were dried over MgSO4 filtered the solvents were removed under reduced pressure Purification of the residue by FC (2:1 hept-EA)

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

Procedure: In a flame dried round-bottomed flask equipped with a magnetic stir bar and a Dean-Stark under inert atmosphere (N2), a solution of 6-bromo-hexan-2-one (3.34 g, 18.65 mmol) in toluene (71.3 mL) was treated with ethylene glycol (10.4 mL, 186.92 mmol) and TsOH (35 mg, 0.19 mmol). The reaction mixture was heated to reflux for 3 h, allowed to cool to rt and sat. aq. NaHCO3 (100 mL) and ether (100 mL) were added and the aq. phase was washed with water (2×100 mL), dried over MgSO4, filtered, and the solvents were removed under reduced pressure to give the title compound. 1H NMR (400 MHz, CDCl3) δ1.34 (s, 3H), 1.50-1.65 (m, 2H), 1.65-1.75 (m, 2H), 1.84-1.98 (m, 2H), 3.43 (t, J=6.8 Hz, 2H), 3.90-4.04 (m, 4H). In a flame dried round-bottomed flask equipped with a magnetic stir bar The reaction mixture was heated to reflux for 3 h the aq. phase was washed with water (2×100 mL) dried over MgSO4 filtered the solvents were removed under reduced pressure

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

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of 4-nitro-2H-[1,2,3]triazole (100 mg, 0.88 mmol) and Cs2CO3 (315 mg, 0.96 mmol) in AcCN (1.0 mL) was treated with a solution of 2-(4-bromo-butyl)-2-methyl-[1,3]dioxolane (215 mg, 0.96 mmol) in AcCN (1.0 mL). The reaction mixture was stirred at 80° C. for 16 h. Water (20 mL), followed by EA (30 mL) were added. The aq. layer was extracted with EA (30 mL) and the combined org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (2:1 hept-EA) gave the title compound: TLC:rf (2:1 hept-EA)=0.33. LC-MS-conditions 02: tR=0.92 min. were added The aq. layer was extracted with EA (30 mL) extracts were dried over MgSO4 filtered the solvents were removed under reduced pressure Purification of the residue by FC (2:1 hept-EA)

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

Procedure: In a flame dried round-bottomed flask equipped with a magnetic stir bar and a Dean-Stark under inert atmosphere (N2), a solution of 6-bromo-hexan-2-one (3.34 g, 18.65 mmol) in toluene (71.3 mL) was treated with ethylene glycol (10.4 mL, 186.92 mmol) and TsOH (35 mg, 0.19 mmol). The reaction mixture was heated to reflux for 3 h, allowed to cool to rt and sat. aq. NaHCO3 (100 mL) and ether (100 mL) were added and the aq. phase was washed with water (2×100 mL), dried over MgSO4, filtered, and the solvents were removed under reduced pressure to give the title compound. 1H NMR (400 MHz, CDCl3) δ1.34 (s, 3H), 1.50-1.65 (m, 2H), 1.65-1.75 (m, 2H), 1.84-1.98 (m, 2H), 3.43 (t, J=6.8 Hz, 2H), 3.90-4.04 (m, 4H). In a flame dried round-bottomed flask equipped with a magnetic stir bar The reaction mixture was heated to reflux for 3 h the aq. phase was washed with water (2×100 mL) dried over MgSO4 filtered the solvents were removed under reduced pressure

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of 5-nitro-1H-pyrazole (2.97 g, 18.68 mmol) and Cs2CO3 (6.67 g, 26.22 mmol) in AcCN (27.0 mL) was treated with a solution of 2-(4-bromo-butyl)-2-methyl-[1,3]dioxolane (5.85 g, 26.22 mmol) in AcCN (27.0 mL). The reaction mixture was stirred at 80° C. for 2.5 h. Water (100 mL) and EA (200 mL) were added to the cooled reaction mixture. The aq. layer was extracted with EA (100 mL) and the combined org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (60:40 hept-EA) gave the title compound. TLC: rf (60:40 hept-EA)=0.17. LC-MS-conditions 02: tR=0.89 min; [M+H]+=256.32. 1H NMR (400 MHz, CDCl3) δ 1.31 (s, 3H), 1.39-1.50 (m, 2H), 1.67-1.75 (m, 2H), 1.92-2.02 (m, 2H), 3.88-3.94 (m, 2H), 3.94-4.00 (m, 2H), 4.22 (t, J=7.0 Hz, 2H), 6.91 (d, J=2.3 Hz, 1H), 7.46 (d, J=2.3 Hz, 1H). The aq. layer was extracted with EA (100 mL) extracts were dried over MgSO4 filtered the solvents were removed under reduced pressure Purification of the residue by FC (60:40 hept-EA)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of 4-nitro-1H-pyrazole (2.10 g, 18.68 mmol) and Cs2CO3 (6.67 g, 20.46 mmol) in AcCN (18.9 mL) was treated with a solution of 2-(4-bromo-butyl)-2-methyl-[1,3]dioxolane (4.15 g, 18.60 mmol) in AcCN (18.9 mL). The reaction mixture was stirred at 80° C. for 2 h. Water (100 mL) was added followed by EA (100 mL). The aq. layer was extracted with EA (200 mL) and the combined org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (50:50 hept-EA) gave the title compound. TLC: rf (50:50 hept-EA)=0.46. LC-MS-conditions 02: tR=0.89 min; [M+H]+=256.36. 1H NMR (400 MHz, CDCl3) δ 1.31 (s, 3H), 1.38-1.53 (m, 2H), 1.65-1.77 (m, 2H), 1.90-2.02 (m, 2H), 3.88-3.94 (m, 2H), 3.94-3.99 (m, 2H), 4.17 (t, J=7.0 Hz, 2H), 8.08 (s, 1H), 8.14 (s, 1H). The aq. layer was extracted with EA (200 mL) extracts were dried over MgSO4 filtered the solvents were removed under reduced pressure Purification of the residue by FC (50:50 hept-EA)

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

Procedure: In a flame dried round-bottomed flask equipped with a magnetic stir bar and a Dean-Stark apparatus under inert atmosphere (N2), a solution of 6-bromo-hexan-2-one (3.34 g, 18.65 mmol) in toluene (71.3 mL) was treated with ethylene glycol (10.4 mL, 186.92 mmol) and TsOH (35 mg, 0.19 mmol). The reaction mixture was heated to reflux for 3 h, allowed to cool to rt and sat. aq. NaHCO3 (100 mL) and ether (100 mL) were added and the aq. phase was washed with water (2×100 mL), dried over MgSO4, filtered, and the solvents were removed under reduced pressure to give the title compound. 1H NMR (400 MHz, CDCl3) δ 1.34 (s, 3H), 1.50-1.65 (m, 2H), 1.65-1.75 (m, 2H), 1.84-1.98 (m, 2H), 3.43 (t, J=6.8 Hz, 2H), 3.90-4.04 (m, 4H). In a flame dried round-bottomed flask equipped with a magnetic stir bar The reaction mixture was heated to reflux for 3 h the aq. phase was washed with water (2×100 mL) dried over MgSO4 filtered the solvents were removed under reduced pressure

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

Procedure: A solution of 1,6-naphthyridine (13.0 g, 0.1 mol) and 6-bromohexan-2-one ethylene ketal (26.8 g, 0.12 mol) in acetonitrile (100 ml) was refluxed for 10 hours. The reaction mixture was evaporated in vacuo, dissolved in methanol (600 ml) and water (200 ml). To the mixture, sodium borohydride (19.5 g, 0.5 mol) was added portionwise over the internal temperature range 0° to 20° C. After stirring overnight at room temperature, the reaction mixture was evaporated in vacuo, water added and extracted with ethyl acetate. The organic layer was dried over anhydrous potassium carbonate, evaporated in vacuo. The resulting residue was dissolved in 1 N-HCl and stirred overnight, neutralized with 33% NaOH solution and extracted with chloroform. The organic layer was dried over anhydrous potassium carbonate, evaporated in vacuo. The residue was purified by alumina column chromatography (eluted with chloroform-methanol (10:1)) and distilled, bp. 157°-158° C./0.6 mmHg, to afford the Compound No. 29 (9.3 g, 40.1%) as a light yellow oil. The reaction mixture was evaporated in vacuo dissolved in methanol (600 ml) range 0° to 20° C the reaction mixture was evaporated in vacuo, water added extracted with ethyl acetate The organic layer was dried over anhydrous potassium carbonate evaporated in vacuo The resulting residue was dissolved in 1 N-HCl stirred overnight extracted with chloroform The organic layer was dried over anhydrous potassium carbonate evaporated in vacuo The residue was purified by alumina column chromatography (eluted with chloroform-methanol (10:1)) distilled bp. 157°-158° C./0.6 mmHg, to afford the Compound No

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