3-propyl-1,4-dihydropyrazol-5-one

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

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

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Propyl-1H-pyrazol-5(4H)-one (1.16 mmol) and 4-chloro-6-methoxyquinoline 1-oxide (0.15 g, 1.16 mmol) were stirred in acetic anhydride (3 mL) at ambient temperature for 30-40 minutes. The reaction mixture was concentrated and the resulting solid was filtered off and washed with a minimum amount of ether. (Z)-4-(4-chloro-6-methoxyquinolin-2(1H)-ylidene)-3-propyl-1H-pyrazol-5(4H)-one (0.06 g, 0.016 mmol) was dissolved in ethanol (1.5 mL) and 4-acetamidothiophenol (0.028 g, 0.016 mmol) was added. The reaction mixture was heated to 180° C. using a microwave reactor for 5-10 minutes. The mixture was then concentrated and the resulting solid filtered and washed with ether to give Example 45. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.71 (t, J=7.33 Hz, 3H) 1.27-1.37 (m, J=7.48, 7.48, 7.48, 7.48, 7.48 Hz, 2H) 2.11 (s, 3H) 2.31 (t, J=7.45 Hz, 2H) 3.96 (s, 3H) 6.83 (s, 1H) 7.42 (d, J=2.78 Hz, 1H) 7.57 (dd, J=9.09, 2.27 Hz, 1H) 7.68 (d, J=8.59 Hz, 2H) 7.87 (d, J=8.59 Hz, 2H) 8.00 (d, J=9.35 Hz, 1H) 10.36 (s, 1H); ESI-MS: m/z calc'd for C24H24N4O3S 448.54. found 449.2 (M+H)+. The reaction mixture was concentrated the resulting solid was filtered off washed with a minimum amount of ether for 5-10 minutes The mixture was then concentrated the resulting solid filtered washed with ether to give Example 45

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

Procedure: Methyl butyrylacetate (4 g, 27.7 mmol) was stirred in ethanol and acetic acid (10:1, 8:0.8 mL) and treated with hydrazine (1.05 mL, 33.3 mmol). After 2 hrs, the resulting solid was filtered off and washed with a minimum amount of acetonitrile to yield 3-propyl-1H-pyrazol-5(4H)-one. Then, the 3-propyl-1H-pyrazol-5(4H)-one (4.68 g, 11.8 mmol) and 4-chloroquinoline N-oxide (1.5 g, 11.8 mmol) were stirred in acetic anhydride (20 mL) at ambient temperature for 30-40 minutes. The reaction mixture was concentrated, and the resulting solid filtered off, washed with a minimum amount of methanol, and treated with hydrazine (0.84 mL, 26.7 mmol) in methanol (12 mL) to yield Example 23 as a solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.97 (t, J=7.33 Hz, 3H) 1.66-1.76 (m, 2H) 3.02 (t, J=7.07 Hz, 2H) 7.62 (t, J=7.58 Hz, 1H) 7.80 (t, J=7.71 Hz, 1H) 7.93 (d, J=8.34 Hz, 1H) 8.10 (d, J=8.34 Hz, 2H); ESI-MS: m/z calc'd for C15H14ClN3O 287.74. found 288.2 (M+H)+. the resulting solid was filtered off washed with a minimum amount of acetonitrile