196811-66-2, 196811-66-2 tert-Butyl 4-carbamothioylpiperazine-1-carboxylate 12093220, apiperazines compound, is more and more widely used in various fields.
196811-66-2, tert-Butyl 4-carbamothioylpiperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated
4-propionylbenzoic acid (890 mg, 5 mmol), NaHCO3 (1.26 g, 15 mmol), and iodomethane (935 uL, 15 mmol) in DMF (10 ml_) were stirred at RT overnight. The mixture was diluted with saturated aqueous NaCI (50 ml_) and extracted with ether (3 x50 ml_). The organic phase was washed with water (50 ml_), dried, and evaporated.Flash chromatography (90 g silica, 2/1 petroleum ether – EtOAc) gave white solids of 4-Propionyl-benzoic acid methyl ester (744 mg, 77%).1 H NMR (CDCI3, 400MHz) delta 1.24 (t, 3H, J = 7 Hz), 3.03 (q, 2H, J = 7 Hz), 3.95 (s, 3H),8.0 and 8.12 (ABq, 4H)4-Propionyl-benzoic acid methyl ester (744 mg, 3.87 mmol), pyrrolidone hydrotribromide (1.98 g), and 2-pyrrolidinone (380 mg, 4.5 mmol) in THF (38 ml_) were heated at 50 0C under nitrogen for 3 h. The mixture was cooled, filtered, concentrated, and then redissolved in ether (50 ml_). The ether solution was washed successively with water (20 ml_), saturated aqueous sodium thiosulphate (20 ml_), saturated aqueous NaCI (20 ml_), and water (2OmL), dried and evaporated to give crude 4-(2-Bromo- EPO propionyl)-benzoic acid methyl ester as a yellow oil (1.025 g) that was used directly in the Hantzsch coupling. This material contained 91% of the desired bromoketone, 5% starting material, and 4% 4-bromo-1-butanol, as determined by 1 H NMR.1 H NMR (CDCI3, 400MHz) delta 1.92 (d, 3H, J = 7 Hz), 3.96 (s, 3H), 5.28 (q, 1 H, J = 7 Hz), 8.07 and 8.14 (ABq, 4H)All of the 4-(2-Bromo-propionyl)-benzoic acid methyl ester above and piperazine-1- carboxylic acid terf-butyl ester (J. Med. Chem., 1998, 5037-5054, 917 mg, 3.73 mmol) were refluxed in 36 ml_ THF at 70 0C for 2 h, under N2. The precipitate was filtered and the filtrate evaporated to give yellow solids. Flash column chromatography (silica, 5/1 petroleum ether – EtOAc) gave 624 mg of 4-[4-(4-Methoxycarbonyl-phenyl)-5-methyl- thiazol-2-yl]-piperazine-1 -ca rboxylic acid tert-butyl ester as a light yellow solid. Chromatography of the precipitate (silica, 2/1 petroleum ether – EtOAc) gave 32 mg more of compound. Total yield is 44%.1 H NMR (CDCI3, 400MHz) delta 1.46 (s, 9H), 2.43 (s, 3H), 3.42, (m, 4H), 3.54 (m, 4H), 3.90 (s, 3H), 7.68 and 8.04 (ABq, 4H).The above methyl ester (564 mg, 1.35 mmol) was heated with 1.35 ml_ 2N NaOH, 5 ml_ THF, and 3.65 ml_ water at 60 0C for 4 h. The reaction mixture was evaporated, poured into 20 ml_ saturated aqueous NaCI and 20 ml_ CH2CI2, and then acidified to pH 3 with 5% citric acid, in an ice bath. The layers were separated and the organic phase was extracted further with 2 x 10 ml_ CH2CI2. The organic phases were combined, washed with water (10 ml_), dried, and evaporated to give 4-[4-(4-Carboxy-phenyl)-5-methyl- thiazol-2-yl]-piperazine-1-carboxylic acid tert-butyl ester as a light yellow solid (537 mg, 98%).1 H NMR (CDCI3, 400MHz) delta 1.48 (s, 9H), 2.47 (s, 3H), 3.47 (m, 4H), 3.57 (m, 4H), 7.74 and 8.12 (ABq, 4H).13C NMR (CDCI3, 100MHz) delta ppm: 12.6, 28.3, 42.8, 48.1 , 80.3, 119.1 , 127.8, 128.2, 130.1 , 140.5, 145.6, 154.6, 167.2, 171.4. LCMS: (M + H)+ 404, (M – H)” 402. EPO 4-[4-(4-Carboxy-phenyl)-5-methyl-thiazol-2-yl]-piperazine-1-carboxylic acid tert-butyl ester (0.421 mmol) was dissolved in 4M HCI in 1 ,4-dioxane, and stirred at room temperature for 1 h. The solvent was then removed under vacuum, and the residue 4-(5-Methyl-2-piperazin-1-yl-thiazol-4-yl)-benzoic acid was suspended in methanol (10 ml) and treated with AcOH/AcONa buffer (pH ~5.5, 5 ml), and formaldehyde (0.547 mmol). The reaction mixture was stirred at room temperature for 1 h, then treated with NaCNBH3 (0.547 mmol) and stirred at room temperature overnight. The solvent was then removed under vacuum, and the residue was purified by column chromatography to afford the title compound (0.403 mmol, 95%). MS(ES) m/z 318 (100%, [M+H]+).
196811-66-2, 196811-66-2 tert-Butyl 4-carbamothioylpiperazine-1-carboxylate 12093220, apiperazines compound, is more and more widely used in various fields.
Reference£º
Patent; MEDIVIR AB; WO2007/6714; (2007); A1;,
Piperazine – Wikipedia
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