3-(2,5-diMethyl-1H-pyrrol-1-yl)-1-Methyl-1H-pyrazole

Accordingly, as shown in step 3-i of Scheme 3, 1-methyl-1H-pyrazol-3-amine (compound 1007, 2.8 g, 28.8 mmol) and 2, 5-hexanedione (3.38 mL, 28.8 mmol) were dissolved into 50 mL of toluene. p-Toluenesulfonic acid (1.4 mmol) was added, the reaction mixture refluxed, and water generated from the reaction collected in a Dean-Stark trap.Step 1) A solution of 1-methyl-1H-pyrazol-3-ylamine (0.92 g, 9.5 mmol) in benzene (4.8 mL) was treated with hexane-2, 5-dione (1.34 mL, 11.4 mmol) and para-toluenesulfonic acid (182 mg, 0.95 mmol) and was heated to 115° C. under Dean-Stark conditions for 4 h. After this time, the reaction was cooled to 25° C., concentrated in vacuo and dried under high vacuum overnight. The resulting residue was dissolved in methylene chloride (100 mL) and was washed with water (1.x.150 mL), dried over sodium sulfate, filtered and concentrated in vacuo. Silica gel column chromatography (ISCO, 80 g, 1:4 ethyl acetate/hexanes) afforded 3-(2, 5-dimethyl-pyrrol-1-yl)-1-methyl-1H-pyrazole (1.57 g, 94percent) as a green oil; ESA solution of 1 -methyl-1 -/-pyrazol-3-amine (2 g, 20.6 mmol, ) in AcOH (50 mL) was treated with 2, 5-hexane dione (4.9 g, 43.29 mmol) at ambient temperature under nitrogen atmosphere. The resulting reaction mixture was heated to 100 °C for 1 h then stirred at ambient temperature for 5 h. The reaction mixture was concentrated under reduced pressure and azeotroped with toluene. The crude product was purified by column chromatography on silica gel using 10percent EtOAc- hexanes eluent to give 3-(2, 5-dimethyl-1 H-pyrrol-1 -yl)-1 -methyl-1 H-pyrazole as a liquid (2.5 g, 69percent). To a solution of 1-methyl-3-aminopyrazole (50 g, 0.52 mol) in toluene (2 L), hexane-2, 5-dione (58.5 g) and acetic acid (12.5 mL) were added. The solution was then refluxed for 3 hours. After the reaction mixture was cooled, water (0.6 L) was added thereto. The mixture was neutralized with sodium carbonate, and then separated. The organic layer was then concentrated. The residue was purified by silica gel chromatography (ethyl acetate/petroleum ether 1:10) to yield 62 as a brown solid (57 g, y. 63percent). To a stirred suspension of 1-methyl-1H-pyrazol-3-amine 76a (0.5 g, 5.1 mmol) in toluene (20 mL) in an round bottom flask fitted with Dean-Stark apparatus was charged with hexane-2, 5-dione (0.70 g, 6.1 mmol) followed by p-toluene sulfonic acid (0.097 g, 0.51 mmol) and the reaction mixture was heated at 115°C for about 6 h. The reaction mixture was cooled to room temperature. Reaction mass was concentrated fully under reduced pressure, residue obtained was dissolved in DCM, given water wash followed by brine wash, dried over Na2504 and concentrated under redcued pressure to obtain 3-(2, 5-dimethyl-1H-pyrrol-1-yl)-1-methyl-1H-pyrazole 76b (0.55 g, 55percent yield) as green oil. 1HNMR (400 MHz, CDC13): 6 7.39 (d, 111), 6.15 (s, 1H), 5.85 (s, 2H), 3.92 (s, 3H), 2.10 (s, 6H), MS: 176.11 (M+H).To a solution of 1-Methyl-1H-pyrazol-3-ylamine (2 g, 20.59 mmol), hexane-2, 5-dione (2.82 g, 24.71 mmol) in toluene (35 ml) was added PTSA.H2O (392 mg, 2.059 mmol).1-methyl-1-methyl -1H- pyrazol-3-amine (3.90g, 40.16mmol) and hexane-2, 5-dione (4.58g, 40.13mmol) in toluene (80mL) was added acetic acid (0.73g, 12.16mmol). The reaction mixture was warmed to 155 deg.] C, stirred overnight, then cooled to room temperature and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (EtOAc / PE (v / v) = 1/10) to give the title compound as a yellow solid (6.90 g of the, yield 98.1percent).

Molecular Weight:175.23
XLogP3:1.8
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:175.110947427
Monoisotopic Mass:175.110947427
Topological Polar Surface Area:22.8
Heavy Atom Count:13
Complexity:173
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes