Category: piperazines

109-07-9, 2-Methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Method 1 1-(t-Butoxycarbonyl)-3-methylpiperazine To a cold (-5¡ã C.) solution of 2-methylpiperazine (5.00 g, 0.05 mole) in 200 mL of CH2Cl2 under Ar was added a solution of di-t-butyl dicarbonate (10.9 g, 0.05 mole) in 100 mL of CH2Cl2 over 1 h. The resulting mixture was stirred at -5¡ã C. for 1 h and then at r.t. for 2 h. The solution was then washed (H2O), dried (Na2SO4) and evaporated to give an oil which was chromatographed (SiO2/ethyl acetate then ethyl acetate-MeOH-NH4OH 10:1:0.1) to give the product (4.30 g, 43percent) as an oil. This material was used without further purification: 1H nmr (200 MHz, CDCl3) delta4.15-3.75 (br s, 2H), 3.0-2.6 (m, 4H), 2.47-2.35 (m, 1H), 1.48 (s, 9H), 1.08 (d, J=6.7 Hz, 3H)., 109-07-9

As the paragraph descriping shows that 109-07-9 is playing an increasingly important role.

Reference£º
Patent; Fabre-Kramer Pharmaceuticals, Inc.; US2009/281114; (2009); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.21655-48-1,cis-2,6-Dimethylpiperazine,as a common compound, the synthetic route is as follows.

To a mixture of 5a (5.0g, 32.44 mmol, 1 equiv) and (2S,6R)-2,6-dimethylpiperazine (3.7g, 32.44 mmol, 1 equiv) in 60 mL DMSO was added K2CO3 (8.97g, 64.88mmol, 2 equiv). The mixture was heated at 110 C for 12h. The reaction mixture was diluted with 120 mL ice water. Ethyl acetate was added and the reaction mixture was partitioned between ethyl acetate and water. The organic phase was washed with water and brine, then dried over anhydrous Na2SO4, filtered and concentrated. The resulting residue was further purified via silica gel chromatography to give ethyl 4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzoate as a white solid (7.25g, 90%). NMR (300MHz, CDCl3) delta 7.85 (d, J=9.0Hz, 2H), 6.79 (d, J=9.0Hz, 2H), 4.26 (q, J=7.1Hz, 2H), 3.60 (d, J=12.0Hz, 2H), 2.96-2.88 (m, 2H), 2.32 (t, J=11.3Hz, 2H), 1.30 (t, J=7.1Hz, 3H), 1.08 (d, J=6.3Hz, 6H). The obtained methyl 4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzoate was dissolved in dichloromethane (DCM) and stirred for 15 min after adding 1 N NaOH (aq) (32.12 mL, 32.12 mmol, 1.1 equiv). Then a solution of di-tert-butyl dicarbonate ester in DCM was added dropwise. The reaction mixture was stirred at room temperature until the starting material was consumed completely. The reaction mixture was then extracted with DCM and the organic phase was washed with saturated NaHCO3 (aq) and brine, then dried over anhydrous Na2SO4, filtered and concentrated. The resulting residue was further purified via silica gel chromatography to give 6a as colorless oil. (10.00 g, 98%). 1H NMR (300 MHz, CDCl3) delta 7.77 (d, J = 8.8 Hz, 2H), 6.68 (d, J = 8.7 Hz, 2H), 4.20-4.08 (m, 4H), 3.44 (d, J = 12.5 Hz, 2H), 2.87 (dd, J = 12.4, 3.8 Hz, 2H), 1.35 (s, 9H), 1.20 (t, J = 7.1 Hz, 3H), 1.14 (d, J = 6.8 Hz, 6H). To a solution of 6a (10.00 g, 28.70 mmol, 1 equiv) dissolved in MeOH was added 1 N NaOH (aq) (57.40 mL, 57.40 mmol, 2 equiv). The mixture was heated at 60 C for 4 h and allowed to cool down to room temperature. The reaction mixture was acidified with 2 NHCl (aq) to adjust PH to 5-6. The resulting precipitate was collected by filtration, washed with water and dried to a constant weight to afford 4-((3R,5S)-4-(tert-butoxycarbonyl)-3,5-dimethylpiperazin-1-yl)benzoic acid (9.79 g, 98%). 1H NMR (300 MHz, DMSO) delta 7.76 (d, J = 8.7 Hz, 2H), 6.97 (d, J = 8.9 Hz, 2H), 4.18-4.05 (m, 2H), 3.75 (d, J = 12.8 Hz, 2H), 2.98 (dd, J = 12.9, 4.3 Hz, 2H), 1.42 (s, 9H), 1.19 (d, J = 6.7 Hz, 6H). The obtained acid (9.79 g, 29.28 mmol, 1 equiv) was dissolved in dry DCM and allowed to cool down to 0 C. DMF (22.57 mL, 292.8 mmol, 10 equiv) and thionyl chloride (4.25 mL, 58.56 mmol, 2 equiv) dissolved in dry DCM were added dropwise to the mixture above. Then the reaction mixture was allowed to warm up to room temperature slowly and left to stir for 2 h. The solvent was removed under reduced pressure at room temperature. Then the residue was redissolved in dry DCM, and was added to the DCM solution of NH4OH (11.28 mL, 292.8 mmol, 10 equiv), which was cooled down to 0 C already. The ice-bath was removed and the reaction mixture was stirred at room temperature for 4 h. The reaction mixture was then extracted with DCM and the organic phase was washed with saturated NaHCO3 (aq) and brine, then dried over anhydrous Na2SO4, filtered and concentrated. The resulting residue was further purified via silica gel chromatography to give 7a as a white solid (4.88 g, 50%). 1H NMR (300 MHz, CDCl3) delta 7.67 (d, J = 8.5 Hz,2H), 6.81 (d, J = 8.7 Hz, 2H), 5.87 (s, 2H), 4.29-4.10 (m, 2H), 3.50 (d, J = 12.3 Hz, 2H), 2.97 (dd, J = 12.3, 3.8 Hz, 2H), 1.43 (s, 9H), 1.25 (d, J = 6.8 Hz, 6H). 14 (8.0 g, 26.69 mmol, 1 equiv), methylamine hydrochloride (2.7 g, 40.04 mmol, 1.5 equiv), EDCl (7.68 g, 40.04 mmol, 1.5 equiv), HOBt (3.61 g, 26.69 mmol, 1.0 equiv) and DIPEA (11.02 mL, 66.72 mmol, 2.5 equiv) were dissolved in dry DCM and the reaction mixture was left to stir at room temperature overnight. The reaction mixture was then extracted with DCM and the organic phase was washed with saturated NaHCO3 (aq) and brine, then dried over anhydrous Na2SO4, filtered and concentrated. The resulting residue was further purified via silica gel chromatography to give 15 as white solid (8.0 g, 95.8%). 1H NMR (300 MHz, CDCl3) delta 8.40 (d, J = 9.2 Hz, 1H), 8.18 (d, J = 5.5 Hz, 1H), 7.81 (d, J = 8.3 Hz, 1H), 7.55 (d, J = 6.8 Hz, 1H), 7.51-7.42 (m, 2H), 7.24 (dd, J = 9.3, 2.3 Hz, 1H), 6.78 (d, J = 7.6 Hz, 2H), 6.05 (d, J = 4.0 Hz, 1H), 3.05 (d, J = 4.9 Hz, 3H). 7a (100 mg, 0.30 mmol, 1 equiv) and 15 (112.56 mg, 0.36 mmol, 1.2 equiv) were dissolved in 10 mL dry dioxane. Then Pd2(dba)3 (27.47 mg, 0.03 mmol, 0.1 equiv), Xantphos (34.72 mg, 0.06 mmol, 0.2 equiv) and Cs2CO3 (195.49 mg, 0.60 mmol, 2 equiv) were added to the mixture above. The reaction mixture was left to stir at 110 C for 5 h under nitrogen atmosphere. The reaction mixture was then extracted with DCM and the organic phase was washed with saturated NaHCO3 (aq) and brine, then dried over anhydrous…, 21655-48-1

As the paragraph descriping shows that 21655-48-1 is playing an increasingly important role.

Reference£º
Article; Wei, Manman; Peng, Xia; Xing, Li; Dai, Yang; Huang, Ruimin; Geng, Meiyu; Zhang, Ao; Ai, Jing; Song, Zilan; European Journal of Medicinal Chemistry; vol. 154; (2018); p. 9 – 28;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

59878-57-8, 1-(Cyclopropylcarbonyl)piperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

59878-57-8, General procedure: Compound 6 (1.0 equiv) with catalytic equivalent KI was dissolved in freshly distilled DMF in an oven-dried round bottom flask. Different aliphatic amines (3.0 equiv) was added dropwise. The reaction mixture was stirred at room temperature for about 4h. After the reaction monitored by TLC was over, water was added to the reaction mixture under stirring, and the suspended mixture was filtered. The crude residue was purified by column chromatography on silica gel to obtain the final products.

As the paragraph descriping shows that 59878-57-8 is playing an increasingly important role.

Reference£º
Article; Chen, Lijuan; Chen, Yong; Deng, Dexin; Liu, Kongjun; Pei, Heying; Tang, Minghai; Xue, Linlin; Yang, Tao; Yang, Zhuang; Ye, Haoyu; Zheng, Shoujun; European Journal of Medicinal Chemistry; vol. 197; (2020);,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.5308-25-8,1-Ethylpiperazine,as a common compound, the synthetic route is as follows.

1-Ethyl-4-(3-nitro-phenyl)-piperazineA mixture of 1-fiuoro-3-nitrobenzene (3.2 mL, 29.7 mmol) and N-ethyl-piperazine (7.6 mL, 59.4 mmol, 2 equiv) is heated to reflux and stirred for 117h. The reaction mixture is allowed to cool to RT and diluted with H2O (40 mL) and DCM/MeOH (9:1 , 80 mL). The aqueous layer is separated and extracted with DCM/MeOH (9:1). The organic phase is washed with brine, dried (Na2SO4), filtered and concentrated. Purification of the crude product by silica gel column chromatography (DCM/MeOH, 1 :0 ? 95:5) affords the title compound as a brown oil: ESI-MS: 236.0 [MH]+; tR= 2.49 min (purity: 99%, system 1 ); TLC: R, – 0.26 (DCM/MeOH, 95:5)., 5308-25-8

The synthetic route of 5308-25-8 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; NOVARTIS AG; NOVARTIS PHARMA GmbH; WO2007/71752; (2007); A2;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

1403898-64-5, (2R,5R)-tert-Butyl 5-(hydroxymethyl)-2-methylpiperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Preparation 10: (2R,5R)-2-Hydroxymethyl-5-methyl-piperazine-1 ,4-dicarboxylic acid 1 – benzyl ester 4-ferf-butyl esterTo (2R,5R)-5-hydroxymethyl-2-methyl-piperazine-1 -carboxylic acid ie f-butyl ester (21 g, 90 mmol) in THF (210 mL) at 3-4 C (ice bath) was added 1 M aqueous NaOH (99.5 mL) and benzyl chloroformate (12.9 mL, 90.43 mmol). After stirring for 1 h at the same temperature, the mixture was left to stir for another 1 h and then warmed to RT. The organic layer was separated and the aqueous phase extracted with EtOAc (2 x 50 mL). The combined organic extracts were washed with saturated brine solution (150 mL), then dried over sodium sulfate, filtered and concentrated. The crude oil was purified by column chromatography on silica gel (gradient elution, 0 – 100%, EtOAc/petrol), to give the title compound (26 g) as a pale yellow oil, used directly in Preparation 1 1 . 1H NMR (Me-d3-OD): 7.47-7.15 (5H, m), 5.26-5.07 (2H, m), 4.25 (2H, s), 4.04-3.88 (1 H, m), 3.83 (1 H, d), 3.61 (2H, bs), 3.31 -3.09 (2H, m), 1 .48 (9H, s), 1.14 (3H, t)., 1403898-64-5

The synthetic route of 1403898-64-5 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; ASTEX THERAPEUTICS LIMITED; WOOLFORD, Alison Jo-Anne; HOWARD, Steven; BUCK, Ildiko Maria; CHESSARI, Gianni; JOHNSON, Christopher Norbert; TAMANINI, Emiliano; DAY, James Edward Harvey; CHIARPARIN, Elisabetta; HEIGHTMAN, Thomas Daniel; FREDERICKSON, Martyn; GRIFFITHS-JONES, Charlotte Mary; WO2012/143726; (2012); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

5747-48-8,5747-48-8, 11-(Piperazin-1-yl)dibenzo[b,f][1,4]thiazepine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Example 11 2-(2-(4-dibenzo[b,f][1,4]thiazepine-11-yl-1-piperazinyl)ethoxy)ethanol OR 11-[4-[2-(2-hydroxyethoxy)ethyl]-1-piperazinyl]dibenzo[b,f][1,4]thiazepine A 1 liter round bottom flask equipped with stirring rod, thermo pocket, water condenser was charged with solution of 11-piperazinyldibenzo[b,f][1,4]thiazepine in toluene 350 cc [63.0 g (0.22 moles)] and the mixture was stirred for 15 min at 25-30 C. Sodium carbonate [41.0 gm (0.39 moles)], tetra butyl ammonium bromide [16.0 gm (0.05 mole)] and 2-(2-chloroethoxy)ethanol [32.0 gm (0.257 moles)] were added at room temperature. The reaction mixture was heated to reflux at 110-112 C. The reaction mixture was maintained at reflux for 10-12 hrs. The reaction mixture was analyzed by HPLC (to check the absence of compound of Formula IV) and was cooled to 25 C. to 30 C., and was added 150 cc DM water. The reaction mixture was then stirred for 30 min at 25-30 C. The layers were separated and the aqueous layer extracted with 50 cc toluene. The extract and the organic layer were combined, to which was added 250 cc water and was acidified with formic acid to obtain a pH of 2-3. The reaction mixture was stirred for 30 min at 25-30 C. The layers were separated and the aqueous layer washed with 100 cc toluene twice. To the aqueous layer was added 250 cc toluene, and the pH adjusted to 8-10 using sodium carbonate. The resulting reaction mixture was stirred for 30 min at 25-30 C. The layers were separated and the aqueous layer extracted with 125 cc toluene. The organic layers were combined and washed with DM water 300 cc twice. The organic layer was distilled off under vacuum below 70 C. to afford 2-(2-(4-dibenzo[b,f]-[1,4]thiazepine-11-yl-1-piperazinyl)ethoxy)ethanol. Purity of 2-(2-(4-dibenzo[b,f]-[1,4]thiazepine-11-yl-1-piperazinyl)ethoxy)ethanol was 99.0% (area % by HPLC).

The synthetic route of 5747-48-8 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; Kansal, Vinod Kumar; Ahmad, Suhail; Lal, Kanhaiya; Patil, Bhatu Tumba; US2008/241949; (2008); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

21655-48-1, cis-2,6-Dimethylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Preparation 6: 1-((2R,6S)-2,6-DimethyI-piperazin-1-yl)-ethanone; STEP A; A solution of BOC2O (1.05 g, 4.8 mmol) in DCM (10 ml) was added dropwise to a stirred solution of (2R,6S)-2,6-dimethyl-piperazine (500 mg, 4.38 mmol) and TEA (1.22 ml, 8.75 mmol) in DCM (20 ml) at 00C. The mixture was stirred at room temperature for 4 h, the solvent was evaporated and the residue was partitioned between water and Et2O. The organic phase was dried over Na2SO4, evaporated in vacuo and the crude reaction mixture was purified by column chromatography (eluent: DCM/MeOH/NH4OH 97:3:0.1) to give 840 mg of (3S,5R)-3,5-dimethyl- piperazine-1-carboxylic acid tert-butyl ester as a yellow oil. Y=89%

21655-48-1, The synthetic route of 21655-48-1 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; DAC S.R.L.; WO2007/113249; (2007); A2;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

129799-08-2, 1-tert-Butyl 3-methyl piperazine-1,3-dicarboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

EXAMPLE 29 Preparation of 6-(2-carbamoyl-4-methylpiperazin-l-yl)-2-(4-(4- (trifluoromethyl) phenoxy)phenyl)pyrimidine-4-carboxamide (Cpd No. 81) Scheme 61 1 -tert-butyl 3-methyl 4-(2-chloro-6-(methoxycarbonyl)pyrimidin-4-yl)piperazine- 1 ,3-dicarboxylate: A mixture of 1-tert-butyl 3-methyl piperazine-l ,3-dicarboxylate (5.133 g, 21.01 mmol), methyl 2,6-dichloropyrimidine-4-carboxylate (4.354 g, 21.03 mmol), and iPr2NEt (4.0 mL, 23.0 mmol) in acetonitrile (50 mL) was heated at 50C for 4 h. After cooling, the reaction mixture was evaporated in vacuo and the residue chromatographed over silica gel with 20-70% EtOAc in hexanes. The product fractions were evaporated in vacuo to give 1-tert-butyl 3-methyl 4-(2-chloro-6- (methoxycarbonyl)pyrimidin-4-yl)piperazine-l,3-dicarboxylate as a very pale yellow powder (6.626 g, 15.97 mmol, 76% yield). LC/MS: m/z= 415.2 [M+H]+., 129799-08-2

The synthetic route of 129799-08-2 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; PURDUE PHARMA L.P.; NI, Chiyou; PARK, Minnie; SHAO, Bin; TAFESSE, Laykea; YAO, Jiangchao; YOUNGMAN, Mark; WO2013/30665; (2013); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.170911-92-9,tert-Butyl 4-(4-aminophenyl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

To a stirred solution of 97 3-(2-chlorophenyl)-7-methylsulfanyl-2H-pyrimido[5,4-e][1,3]oxazin-4-one (130 mg, 0.423 mmol, 1.0 eq) in 5 mL of 24 toluene was added 25 m-CPBA (224 mg, 0.84 mmol, 2.0 eq) and stirred at rt for 30 min. 66 Tert-butyl 4-(4-aminophenyl)piperazine-1-carboxylate (117 mg, 0.423 mmol, 1.0 eq) and 27 DIPEA (163 mg, 1.27 mmol, 3.0 eq) were added and allowed to stir at rt for 12 h. Reaction was monitored by LCMS. After completion of reaction, solvent was removed under reduced pressure. Residue was diluted with saturated NaHCO3 solution and extracted with CH2Cl2 (100 mL¡Á2). Combined organic layer was washed with brine solution (50 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure to give crude product which was purified by flash chromatography to afford 100 tert-butyl 4-[4-[[3-(2-chlorophenyl)-4-oxo-2H-pyrimido[5,4-e][1,3]oxazin-7-yl]amino]phenyl]piperazine-1-carboxylate (120 mg, 52.8%). LCMS: 296 [M+1]+, 170911-92-9

The synthetic route of 170911-92-9 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; giraFpharma LLC; Chakravarty, Sarvajit; PHAM, Son Minh; Kankanala, Jayakanth; AGARWAL, Anil Kumar; PUJALA, Brahmam; SONI, Sanjeev; ARYA, Satish K.; PALVE, Deepak; KUMAR, Varun; (360 pag.)US2019/106436; (2019); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

630125-91-6,630125-91-6, 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

To a stirred solution of 4-chloro-3-nitrobenzoic acid (1.0 g, 4.97 mmol) in dichioromethane(10 mL) were added oxalyl chloride (500 jiL, 5.30 mmol) followed by catalytic amount ofDMF and the mixture was stirred at RT for 2 h. The mixture was concentrated under reducedpressure and the residue was dissolved in dichloromethane. The solution was cooled to 0 C;4-((4-ethylpiperazin- 1 -yl)methyl)-3 -(trifluoromethyl)aniline (Intermediate Cl) (1.0 g, 3.30mmol) was added to the reaction mixture followed by DIPEA (1.5 mL, 8.30 mmol). The resultant mixture was stirred overnight at RT. The mixture was diluted with water and extracted twice with ethyl acetate. The combined organic extracts were washed with saturated sodium bicarbonate solution, water and brine. The solution was dried over anhydrous sodiumsulfate, filtered and concentrated. The residue thus obtained was purified by columnchromatography to yield 1.43 g of the desired product. ?H NMR (400 MHz, DMSO-d6) oe0.98 (t, J 7.2 Hz, 3H), 2.28-2.39 (m, 1OH), 3.57 (s, 2H), 7.74 (d, J 8.4 Hz, 1H), 7.98-8.04(m, 2H), 8.16 (s, 1H), 8.27 (dd, J, = 2.4 Hz, J2 = 8.4 Hz, 1H), 8.65 (s, 1H), 10.77 (s, 1H).

The synthetic route of 630125-91-6 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; GLENMARK PHARMACEUTICALS S.A.; PATEL, Vinod; REDDY, Venkateshwar; GHARAT, Laxmikant Atmaram; CHAUDHARI, Sachin Sundarlal; DAS, Sanjib; VELGALETI, Ranganadh; SHAH, Daisy Manish; BAJPAI, Malini; (262 pag.)WO2018/215668; (2018); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics