1,3-Dimethyl-1H-pyrazol-5-ol

white to light yellow crystal powde

3.16 General procedure: A solution of ethyl acetoacetate or benzoylacetate (0.01 mol) in 20 mL ethanol was added to the methylhydrazine (0.02 mol) dropwise under the ice bath. Then the mixture was refluxed at 80 °C for 5 h. After cooling, filtered and dried the precipitate. The solid obtained was pure and did not need recrystallization. The compound 2a obtained gave the yield of 61percent, and the melting point of 2a was determined as 211-212 °C, which was reported as 213 °C in the reference [13]. The compound 2b obtained gave the yield of 67 percent, and the melting point of 2b was determined as 117-118 °C (116-117 °C was reported in the reference [17]).To a mixture of methyl acetoacetate (70 g, 0.6 mol) in ethanol (500 ml) in a round bottom flask was added drop wise methyl hydrazine (27.6 g, 0.6 mol) with an ice-water bath to keep the temperature below 40° C. The resulting mixture was then stirred at RT for overnight. The solvent was then removed under rotary evaporator to dryness, the solid product was further dried under vacuum, an off-white solid product B (66 grams) was obtained, and used without further purification in next dye formation step.The following compounds may be mentioned as examples of heterocycles of the formula (III): ... 1-{2-(ethoxycarbonyl)-ethyl}-imidazole, 1-(dimethylaminocarbonylmethyl)-imidazole, 1-{2-(dimethylaminocarbonyl)-ethyl}-imidazole, 1-(4, 6-dimethoxypyrimidin-2-yl)-imidazole, At room temperature, add 1, 3-dimethyl-1H-pyrazole-5-ol (1.12 g, 0.01 mol), (3.95 g, 0.05 mol) pyridine was sequentially dissolved in 20 ml of dichloromethane. The low temperature bath was cooled to 3 C.To the above mixture, 7-chloro-3-(methylsulfonyl)quinoline-8-carbonyl chloride (6.08 g, 0.02 mol) was added dropwise at a dropping rate of 2 drops per 30 seconds.After the dropwise addition was completed, the mixture was naturally warmed to room temperature and reacted for 5 hours. To the reaction mixture was added 10 ml of a saturated aqueous sodium hydrogen carbonate solution, and dichloromethane (3 * 15 ml) was extracted. The organic layers were combined, washed with water (1 * 15 ml), washed with saturated brine, and dried over anhydrous magnesium sulfate.The product was desolvated under reduced pressure to obtain 3.03 g of the product with a yield of 80%.At room temperature, 1, 3-dimethyl-1H-pyrazole-5-ol (1.12 g, 0.01 mol) and (1.58 g, 0.02 mol) pyridine were sequentially dissolved in 20 ml of dichloromethane.The low temperature bath was cooled to -5 C. To the above mixture was added dropwise 7-chloro-3-(trifluoromethyl)quinoline-8-carbonyl chloride (4.10 g, 0.014 mol), The dropping rate was 5 drops / 30 seconds. After the addition was complete, the mixture naturally rose to room temperature and reacted for 5 hours. To the reaction mixture was added 10 ml of a saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with dichloromethane (3 * 15 ml). The organic layers were combined, Wash with water (1 * 15ml), saturated brine, and dry over anhydrous magnesium sulfate.The product was dissolved under reduced pressure to obtain 2.96 g of the product with a yield of 80%At room temperature, 1, 3-dimethyl-1H-pyrazole-5-ol (1.12 g, 0.01 mol) and (5.05 g, 0.05 mol) triethylamine were sequentially dissolved in 20 ml of dichloromethane.The low temperature bath was cooled to 0 C. 7-Chloro-3-nitroquinoline-8-carbonyl chloride (5.43 g, 0.02 mol) was added dropwise to the above mixture, and the dropping rate was 3 drops / 30 seconds. After the dropwise addition, the mixture naturally rose to room temperature and reacted for 5 hours. .To the reaction mixture was added 10 ml of a saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with dichloromethane (3 * 15 ml). The organic layers were combined, Wash with water (1 * 15ml), saturated brine, and dry over anhydrous magnesium sulfate.The product was desolvated under reduced pressure to obtain 2.77 g of the product with a yield of 80%At room temperature, 1, 3-dimethyl-1H-pyrazole-5-ol (1.12 g, 0.01 mol) and (2.02 g, 0.02 mol) triethylamine were sequentially dissolved in 20 ml of dichloromethane.The low temperature bath was cooled to 3 C. To the above mixture, 5-(methylsulfonyl)quinoline-8-carbonyl chloride (2.83 g, 0.0105 mol) was added dropwise at a drop rate of 1 drop / 30 seconds. After the dropwise addition, the mixture naturally rose to room temperature and reacted for 5 hours. .To the reaction mixture was added 10 ml of a saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with dichloromethane (3 * 15 ml). The organic layers were combined, Wash with water (1 * 15ml), saturated brine, and dry over anhydrous magnesium sulfate.The product was desolvated under reduced pressure to obtain 2.76 g of the product with a yield of 80%At room temperature, 1, 3-dimethyl-1H-pyrazole-5-ol (1.12 g, 0.01 mol) and (4.14 g, 0.03 mol) potassium carbonate were sequentially dissolved in 20 ml of dichloromethane.The low temperature bath was cooled to -3 C. To the above mixture, quinoline-8-carbonyl chloride (2.87 g, 0.015 mol) was added dropwise at a drop rate of 5 drops / 30 seconds. After the dropwise addition was completed, the mixture naturally rose to room temperature and reacted for 4 hours.To the reaction mixture was added 10 ml of a saturated aqueous sodium hydrogen carbonate solution, and dichloromethane (3 * 15 ml) was extracted. The organic layers were combined, washed with water (1 * 15 ml), washed with saturated brine, and dried over anhydrous magnesium sulfate.The product was dissolved under reduced pressure to obtain 2.13 g of the product with a yield of 80%At room temperature, 1, 3-dimethyl-1hydro-pyrazole-5-ol (1.12 g, 0.01 mol) and (1.12 g, 0.02 mol) potassium hydroxide were sequentially dissolved in 20 ml of dichloromethane.The low temperature bath was cooled to -2 C. 7-chloro-3-methylquinoline-8-carbonyl chloride (4.80 g, 0.02 mol) was added dropwise to the above mixture, and the dropping rate was 1 drop per 30 seconds. After the dropwise addition, the mixture naturally rose to room temperature and reacted for 4 hours. .To the reaction mixture was added 10 ml of a saturated aqueous sodium hydrogen carbonate solution, and dichloromethane (3 * 15 ml) was extracted. The organic layers were combined, washed with water (1 * 15 ml), washed with saturated brine, and dried over anhydrous magnesium sulfate.The product was dissolved under reduced pressure to obtain 2.39 g of the product, and the yield was 76%At room temperature, 1, 3-dimethyl-1H-pyrazole-5-ol (0.65 g, 0.0058 mol) and (1.21 g, 0.012 mol) triethylamine were sequentially dissolved in 20 ml of dichloromethane.The low temperature bath was cooled to 3 C.To the above mixture was added dropwise 3-chloro-7-(methylsulfonyl)-5-(trifluoromethyl)quinoline-8-carbonyl chloride (2.23 g, 0.006 mol), The dropping rate was 4 drops / 30 seconds. After the addition was complete, the mixture naturally rose to room temperature and reacted for 5 hours.To the reaction mixture was added 10 ml of a saturated aqueous sodium hydrogen carbonate solution, and dichloromethane (3 * 15 ml) was extracted. The organic layers were combined, washed with water (1 * 15 ml), washed with saturated brine, and dried over anhydrous magnesium sulfate.The product was dissolved under reduced pressure to obtain 1.95 g of the product with a yield of 75%

Molecular Weight:112.13
XLogP3:0.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:112.063662883
Monoisotopic Mass:112.063662883
Topological Polar Surface Area:32.3
Heavy Atom Count:8
Complexity:151
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes