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CAS No. : | 184177-83-1 | MDL No. : | MFCD11977288 |
Formula : | C30H35N5O3 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | QLRPRKJUMRQTOV-IADCTJSHSA-N |
M.W : | 513.63 | Pubchem ID : | 46223297 |
Synonyms : |
|
Chemical Name : | 1-((2S,3S)-2-(Benzyloxy)pentan-3-yl)-4-(4-(4-(4-hydroxyphenyl)piperazin-1-yl)phenyl)-1H-1,2,4-triazol-5(4H)-one |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With triethylamine; In 1,4-dioxane; at 90 - 100℃; for 24h; | mixture of N?-((2S,3S)-2-(benzyloxy)pentan-3-yl)formohydrazide compound of formula-17 (45.5 g) obtained in example-13, dioxane (500 ml) added <strong>[184177-81-9]phenyl 4-(4-(4-hydroxyphenyl)piperazin-1-yl)phenylcarbamate</strong> compound of formula-19 (50 g) was heated to 90-100 C. Triethylamine (26 g) was added to the reaction mixture at 90-100 C. over a period of 1 hour and stirred for 24 hours at 90-100 C. After completion of the reaction, the reaction mixture was cooled to 25-30 C. and dichloromethane was added to the reaction mixture. Filtered the reaction mixture through hyflow bed and washed with dichloromethane. Water was added to the filtrate. Both organic and aqueous layers were separated and the aqueous layer was extracted with dichloromethane. Both organic layers were combined and washed with 2% sodium hydroxide solution followed by water, and then with 5% hydrochloric acid solution followed by water and 5% NaHCO3 solution washing. Distilled off the solvent from organic layer under reduced pressure to get the title compound. Isopropyl alcohol (75 ml) was added to the obtained compound and the reaction mixture was cooled to 25-30 C. The reaction mixture was stirred for 6 hours at 25-30 C. Filtered the solid, washed with isopropyl alcohol and then dried to get the title compound. Yield: 28 g; Purity by HPLC: 97.67%; Impurity-A: 0.37%b) Purification of Compound of Formula-20 The obtained compound of formula-20 (30 g) was dissolved in methanol (960 ml) by heating at 60-65 C. The reaction mixture was cooled to 25-30 C. and stirred for 30 minutes at the same temperature. Filtered the precipitated solid and dried to get the pure compound of formula-20. Yield: 70%; Purity by HPLC: 99.15%; Impurity-A: 0.09% |
0.89 kg | With triethylamine; In 1,4-dioxane; at 90 - 95℃;Large scale; | N'-[(l S,2S)-2-(Benzyloxy)-l-ethylpropyl]formic hydrazide (1 kg) and 1,4- Dioxane (5 lit) were added to the flask at room temperature along with Phenyl 4- (4-(4-hydroxyphenyl)piperazin-l-yl)phenylcarbamate (1.4 kg). The reaction mass was heated to 90-95C and Triethylamine (0.89 lit) was slowly added and stirred for 1 hr and maintained for 12-18 hrs. TLC was checked for intermediate and cooled to Room temperature and Dichloromethane (20 lit) was charged and filter through the Hyflow bed and washed with Dichloromethane (5 lit). Water (4 lit) was added and stirred for 10 min. Aqueous layer and Organic layer were separated and organic layer was washed with brine solution. Organic layer was separated and dried with Sodium sulphate and distilled completely under vacuum at below 50C and co- distilled with Toluene (1 lit) and Isopropyl alcohol (1 lit). Isopropyl alcohol (2.5 lit) was added to the crude and maintained at 65-70C for 1 hr, then cooled to Room temperature, stirred for 30 min and cooled to 10-15C, and then filtered and washed with Isopropyl alcohol (0.5 lit).Out Put: 0.89 kg; HPLC: 97%. |
With triethylamine; In 1,4-dioxane; at 90 - 100℃; for 24h; | A mixture of compounds 4 (18.0 g, 0.046 mol), 5 (16.38 g, 0.069 mol), and dioxane (180 mL) was heated to 90-100 C. Triethylamine (9.36 g, 0.092 mol) was added to the reaction mixture and then stirred for 24 h at 90-100 C. After the completion of the reaction, the reaction mixture was cooled to 25-30 C and dichloromethane (25 mL) was added to the reaction mixture. Compound 1 was obtained by filtration and concentration under vacuo and stirred in isopropyl alcohol (27 mL) at 25-30 C for 6 h. Pure compound 1 was got by recrystallization with methanol. 1H NMR (DMSO-d6, 400 MHz): delta 0.793 (t, 3H, CH3), 1.242 (d, 3H, CH3), 1.765 (q, 2H, CH2), 3.122 (t, 4H, piperazine-CH2), 3.327 (t, 4H, piperazine-CH2), 3.745 (m, 1H, N-CH), 3.990 (m, 1H, O-CH), 4.275-4.544 (d, 2H, Ar-CH2), 6.691 (d, 2H, Ar-H), 6.869 (d, 2H, Ar-H), 7.119 (d, 2H, Ar-H), 7.172 (q, 2H, Ar-H), 7.232 (m, 3H, Ar-H), 7.476 (d, 2H, Ar-H), 8.323 (s, 1H, N2C-H), 8.787 (s, 1H, Ar-OH). HRMS (ESI+): m/z: calcd for C30H35N5O3: 536.2638 [M+Na+]; found: 536.2619. IR (KBr, lambda, cm-1): 3468.1 (s), 1678.2 (s), 1605.1 (m), 1485.07 (s), 1231.9 (s), 1115.4 (s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77.4% | Will be 4.36kgN '- ((2S, 3S) -2-benzyloxy) pentyl-3-formylhydrazide oxalate(VI)And 45.36 kgDioxane into the 100L glass reactor,Stir, add 3.45kgN, N-diisopropylethylamine. Stirring for 1 to 1.5 hours,Add another 5.47kgPhenyl (4- (4- (4-hydroxy) -1-piperazinyl) phenyl) carbamate(V).After the addition is complete, the temperature is raised to 80 ± 5 C for 24 to 30 hours. TLC monitoring.After the reaction is completed, the system is cooled to 15 ~ 25 ,57.79 kg of dichloromethane and 21.81 kg of pure water were added and stirred for 10 to 20 minutes.Collect the lower organic phase and discard the aqueous phase.The organic phase was transferred to a 100 L glass reactor, and 21.81 kg of purified water was added to the autoclave,Stirring for 10 to 20 minutes, standing and stratifying, collecting the lower organic phase and discarding the aqueous phase. The organic phase was transferred to a 100 L glass reactor. Saturated aqueous sodium chloride solution (6.54 kg of sodium chloride was dissolved in purified water 21.81 kg) was added and stirred for 10 to 20 minutes. The layers were allowed to stand and the organic phase was collected and the aqueous phase was discarded.The organic phase was transferred to a 20 L rotary vial, and at a vacuum of -0.08 to -0.1 MPa,Control the temperature of 30 ~ 40 , concentrated to remove the dichloromethane, to the solvent-free distillation. A brown solid was obtained.The solid was transferred to a 100 L glass autoclave, 32.27 kg of methyl t-butyl ether was added, and the mixture was heated to 50 to 60 C for 0.5 to 1 hour, cooled to 20 ± 5, and stirred for 2 to 3 hours. Centrifuge the filter to the basicSolvent-free, filter cake with 12.91kg methyl tert-butyl ether leaching, centrifugal rejection to the basic solvent-free effluent. Will be all wet goodsAt a vacuum of -0.08 to -0.1 MPa,Control temperature 40 ~ 50 Drying under reduced pressure 6 to 10 hours. A gray solid5.31kg, that is2 - ((2S, 3S) -2- (benzyl) -3-pentyl) -4- (4- (4-(4-hydroxy) -1-piperazine) phenyl)-2,4-dihydro-3-dihydro-1,2,4-triazol-3-one (III), HPLC purity: 98.8%, yield: 77.4% |
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