3-methylfuran-2-carbonyl chloride

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

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

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

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

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-1-(4-aminophenyl)-4-methylpyridin-2(1H)-one (25 mg, 0.075 mmol) was dissolved in THF (2 mL) and NEt3 (3 mL) and then treated with 3-methylfuran-2-carbonyl chloride (13 mg, 0.090 mmol). The reaction was heated to 40° C. and allowed to stir for 3 h. The reaction was cooled and then extracted with EtOAc (3ט10 mL) and water (˜10 mL). The combined organic layers were then washed with ˜20 mL of NaHCO3(aq). The organic layers were then dried over anhydrous Na2SO4 (s), filtered and the concentrated in vacuo. The crude mixture was purified over silica (EtOAc/Hexanes gradient). Following concentration of the appropriate fractions the title compound was isolated as a grey solid (25 mg, 76%). 1H NMR (DMSO) δ: 9.52 (s, 1H), 7.92 (s, 1H), 7.80(m, 1H), 7.42-7.52 (m, 2H), 7.41 (m, 1H), 7.24-7.32 (m, 2H), 6.66 (m, 1H), 6.28 (s, 2H), 6.14 (m, 1H), 4.01 (br. s, H), 3.24 (s, 2H), 2.67 (t, J=5.3 Hz, 2H), 2.35 (s, 3H), 2.20 (s, 3H). The reaction was cooled extracted with EtOAc (3ט10 mL) and water (˜10 mL) The combined organic layers were then washed with ˜20 mL of NaHCO3(aq) The organic layers were then dried over anhydrous Na2SO4 (s) filtered the concentrated in vacuo The crude mixture was purified over silica (EtOAc/Hexanes gradient)

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-1-(4-aminophenyl)-4-methylpyridin-2(1H)-one (25 mg, 0.075 mmol) in2 mL of THF under N2(g) containing 3 mL of NEt3 was treated with 3-methylfuran-2-carbonyl chloride (13 mg, 0.090 mmol). The reaction mixture was heated to 40° C. and allowed to stir for 3 h. The reaction was cooled and then extracted with EtOAc (3ט10 mL) and water (˜10 mL). The combined organic layers were then washed with ˜20 mL of NaHCO3 (aq). The organic layers were then dried over anhydrous Na2SO4, filtered and then concentrated in vacuo. The crude mixture was purified over silica (EtOAc/Hexanes gradient). Following concentration of the appropriate fractions the title compound was collected as a grey solid (25 mg, 76%). 1H NMR (DMSO) δ: 9.52 (s, 1H), 7.92 (s, 1H), 7.81 (d, J=5.6 Hz, 1H), 7.45-7.52 (m, 2H), 7.41 (d, J=6.7 Hz, 1H), 7.24-7.31 (m, 2H), 6.65 (d, J=5.6 Hz, 1H), 6.28 (s, 2H), 6.17 (d, J=7.0 Hz, 1H), 3.96 (br. S, H), 3.29 (s, 2H), 2.66(t, j=5.3 Hz, 2H), 2.35 (s, 3H), 2.18 (s, 3H). The reaction was cooled extracted with EtOAc (3ט10 mL) and water (˜10 mL) The combined organic layers were then washed with ˜20 mL of NaHCO3 (aq) The organic layers were then dried over anhydrous Na2SO4 filtered concentrated in vacuo The crude mixture was purified over silica (EtOAc/Hexanes gradient) was collected as a grey solid (25 mg, 76%)

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-1-(4-aminophenyl)-4-methylpyridin-2(1H)-one (25 mg, 0.075 mmol) in2 mL of THF under N2(g) containing 3 mL of NEt3 was treated with 3-methylfuran-2-carbonyl chloride (13 mg, 0.090 mmol). The reaction mixture was heated to 40° C. and allowed to stir for 3 h. The reaction was cooled and then extracted with EtOAc (3ט10 mL) and water (˜10 mL). The combined organic layers were then washed with ˜20 mL of NaHCO3 (aq). The organic layers were then dried over anhydrous Na2SO4, filtered and then concentrated in vacuo. The crude mixture was purified over silica (EtOAc/Hexanes gradient). Following concentration of the appropriate fractions the title compound was collected as a grey solid (25 mg, 76%). 1H NMR (DMSO) δ: 9.52 (s, 1H), 7.92 (s, 1H), 7.81 (d, J=5.6 Hz, 1H), 7.45-7.52 (m, 2H), 7.41 (d, J=6.7 Hz, 1H), 7.24-7.31 (m, 2H), 6.65 (d, J=5.6 Hz, 1H), 6.28 (s, 2H), 6.17 (d, J=7.0 Hz, 1H), 3.96 (br. S, H), 3.29 (s, 2H), 2.66(t, j=5.3 Hz, 2H), 2.35 (s, 3H), 2.18 (s, 3H). The reaction was cooled extracted with EtOAc (3ט10 mL) and water (˜10 mL) The combined organic layers were then washed with ˜20 mL of NaHCO3 (aq) The organic layers were then dried over anhydrous Na2SO4 filtered concentrated in vacuo The crude mixture was purified over silica (EtOAc/Hexanes gradient) was collected as a grey solid (25 mg, 76%)

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

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

Procedure: The compound was obtained by following the same process as in Example 2 from a mixture of 1-(3-phenylpropyl)-3-methylpiperazine, 3-methyl-2-furoyl chloride and benzene. The compound was obtained

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

Procedure: The compound was obtained by following the same process as in Example 2 from a mixture of trans-1-(3-phenylpropyl)-2,5-dimethylpiperazine, 3-methyl-2-furoyl chloride and benzene. The compound was obtained

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

Procedure: To a stirred flask containing excess concentrated ammonium hydroxide was added gradually 50 g of 3-methyl-2-furoyl chloride. The resulting mixture was extracted with dichloromethane. The extracts were dried, then evaporated to provide solid 3-methylfuran-2-carboxamide. The resulting mixture was extracted with dichloromethane The extracts were dried evaporated

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