Tag: M.W:200-300

694499-26-8,With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.694499-26-8,4-((4-Methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline,as a common compound, the synthetic route is as follows.

Unit Operation 3. 1: Drying Reaction Mixture AP25047, AP24592, and 2-methyl tetrahydrofuran (2-Me-THF) are charged to a reactor. The mixture is concentrated at reduced pressure to a target volume. Additional 2-methyl tetrahdyrofuran is added and the distillation repeated. Following another charge of 2-methyl tetrahydrofuran and a distillation cycle, the water content of the mixture is determined in IPC- 1 (KF). If the IPC-1 criterion is met, the process is continued to Unit Operation 3.2. Unit Operation 3.2: Reaction The suspension is maintained with stirring at a target temperature of 13 – 23C range while potassium fe -butoxide (KOfBu) is charged. After a period of not less than 3 hours, the reaction progress is determined by HPLC (IPC-2). If the IPC criterion is met, the process is continued to Unit Operation 3.3. Unit Operation 3.3: Quench and Extractions The reaction mixture is diluted with 2-methyltetrahydrofuran (2-Me-THF), and quenched by the addition of aqueous sodium chloride solution. The organic layer is separated and the aqueous layer is extracted twice with 2-methyl tetrahydrofuran. The combined organic layers are sequentially washed with aqueous sodium chloride and water. The organic layer is then aged at 15 – 30C. Unit Operation 3.4: Concentration / Solvent Exchange After aging (see Unit Operation 3.3), the mixture is passed through a cartridge filter and concentrated under vacuum to a target volume. 1 -Propanol is charged and allowed to stir at elevated temperature to furnish a solution, which is distilled under vacuum to a target volume and then cooled slowly to a temperature range of 20 – 30C. Unit Operation 3.5: Crystallization The product solution in 1 -propanol is aged with stirring at a temperature of 20 – 30C until the presence of solids is visually observed. Acetonitrile is charged to the suspension with stirring and the resulting suspension is aged for an additional 60 – 120 minutes at 20 – 30C with agitation prior to isolation in the next Unit Operation. Unit Operation 3.6: Isolation / Drying The slurry generated in Unit Operation 3.5 is isolated under vacuum in a filter/dryer. The solids are washed twice with a mixture of 1-propanol and acetonitrile. The solids are then dried under vacuum and monitored by IPC-3 (LOD, gravimetric). If the IPC criterion is met, the product is discharged as an off-white to yellow solid and packaged in double polyethylene bags for storage at ambient temperatures.

694499-26-8 4-((4-Methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline 46838908, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; ARIAD PHARMACEUTICALS, INC.; MURRAY, Christopher, K.; ROZAMUS, Leonard, W.; CHABER, John, J.; SHARMA, Pradeep; WO2014/93579; (2014); A2;,
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.78551-60-7,tert-Butyl 4-benzyl-3-oxopiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

78551-60-7, To a solution of the product of Step 8 (261 mg, 0.900 mmol) in anhydrous THF(5 ml) in a dry ice-acetone bath was added 2M LDA (0.45 ml) and the mixture wasstirred for 1 h. A solution of the above aldehyde in THF (5 ml) was added and themixture was stirred in the dry ice-acetone bath for 2 h. The reaction was quenchedwith saturated NH4CI (4 ml), diluted with CH2CI2 (50 ml), and washed with water (30ml). The organic layer was extracted with saturated NH4CI and brine, dried (MgSO4),concentrated, and purified by PTLC (5% MeOH/CH2CI2) to give the product (100 mg,48%). MS m/e 699 (M+H)+

78551-60-7 tert-Butyl 4-benzyl-3-oxopiperazine-1-carboxylate 10891590, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; SCHERING CORPORATION; WO2006/14944; (2006); 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.120737-78-2,tert-Butyl 2-methylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

A mixture of ethyl 4,6-dimethyl-2-(4-methylpyridin-3-yl)pyrimidine-5-carboxylate (23)(23 mg, 85 mmol) and lithium hydroxide (50 mg, 2.09 mmol) in ethanol (3 mL) was heated at reflux for 3 h. The solvent was removed in vacuo before the residue was purified via reverse phase(C18) HPLC with a gradient elution of H2O/MeOH (100/0% to 10/90%) to afford compound 27 as an orange-brown solid (18 mg, 87%). 1HNMR (D2O, MeOD) d: 8.77 (s, 1H), 8.43 (d, J4.8 Hz, 1H), 7.39 (d,J4.8 Hz, 1H), 2.59 (s, 6H), 2.53 (s, 3H). 13C NMR (D2O, MeOD) d:170.5, 163.2, 162.6, 150.8, 149.8, 149.0, 136.3, 133.8, 127.5, 22.3, 20.4.LRMS (ESI): m/z 244.1 [MH] (100%); (ESI): m/z 242.0 [MH](100%).A solution of 4,6-dimethyl-2-(4-methylpyridin-3-yl)pyrimidine-5-carboxylic acid (27) (40 mg, 0.16 mmol), ()-tert-butyl 2-methylpiperazine-1-carboxylate45 (36 mg, 0.18 mmol), HOBt(24 mg, 0.18 mmol), EDCI (36 mg, 0.18 mmol) and DIPEA (0.08 mL,0.33 mmol) in DCM (10 mL) was stirred at room temperature for 18 h. The reaction mixture was diluted in H2O, extracted with DCM (310 mL), and the combined organic layers concentrated to 3 mL.To the solution was then added 10 drops of TFA before stirring for 3 h. The reaction mixture was then extracted with H2O (33 mL)and the combined aqueous layers freeze dried. The residue was purified via reverse phase (C18) HPLC with a gradient elution ofH2O/MeOH (100/0% to 10/90%), to afford the desired product asa pale yellow solid (4 mg, 7%) as a mixture of conformers. 1H NMR (MeOD) d: 8.44 (br s, 1H), 7.64e7.58 (m, 1H), 7.45 (m, 1H), 7.15e7.07(m, 1H), 4.59 (m, 2H), 3.95 (br s, 2H), 3.63e3.06 (complex, 6H), 2.39(br s, 3H), 1.32 (m, 3H). 13C NMR (MeOD) d: 157.0, 148.9, 147.8,139.2, 129.7, 129.4, 127.4, 127.0, 125.2, 123.4, 123.1, 113.6, 113.3, 52.0,51.9, 47.1, 30.7, 19.9, 17.1, 16.9. HRMS (APCI): m/z calcd forC18H24N5O [MH]: 326.1981, found: 326.1978; (APCI): m/z calcdfor C19H22N4O [MH]: 324.1824, found: 324.1829., 120737-78-2

The synthetic route of 120737-78-2 has been constantly updated, and we look forward to future research findings.

Reference：
Article; Lim, Zelong; Duggan, Peter J.; Wan, Soo San; Lessene, Guillaume; Meyer, Adam G.; Tuck, Kellie L.; Tetrahedron; vol. 72; 9; (2016); p. 1151 – 1160;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

278788-66-2, (R)-tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Tert-butyl (R)-3-(hydroxymethyl)piperazine-1-carboxylate (384 mg, 1.78 mmol) was added to a mixture of 53 7-bromo-4,6-dichloro-3-nitroquinoline (260 mg, 0.81 mmol) and 56 DIPEA (0.316 ml, 1.78 mmol) in NMP (4 ml). The mixture was heated at 75 C. for 2 hours, then allowed to cool to room temperature. The mixture was partitioned between ethyl acetate (100 ml) and water (100 ml). The aqueous layer was extracted with ethyl acetate (100 ml) and the extracts combined with the organic layer. The combined organics were washed sequentially with water (2×100 ml) and saturated brine (50 ml), then dried and evaporated to dryness to give a brown gum. The crude product was purified by flash silica chromatography, elution gradient 20 to 40% 57 EtOAc in 58 heptane. Pure fractions were evaporated to dryness to afford 59 tert-butyl (R)-4-(7-bromo-6-chloro-3-nitroquinolin-4-yl)-3-(hydroxymethyl)piperazine-1-carboxylate (218 mg, 54%) as a yellow solid. 1H NMR (500 MHz, DMSO, 27 C.) 1.43 (9H, s), 3.34-3.53 (5H, m), 3.64 (3H, d), 4.34-4.42 (1H, m), 4.58 (1H, t), 8.38 (1H, d), 8.49 (1H, s), 9.05 (1H, s). m/z: ES+ [M+H]+ 501.

278788-66-2, 278788-66-2 (R)-tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate 24820286, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; ASTRAZENECA AB; Kettle, Jason Grant; Bagal, Sharanjeet; Robb, Graeme Richard; Smith, James Michael; Goldberg, Frederick Woolf; Cassar, Doyle Joseph; Feron, James Lyman; US2019/177338; (2019); 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.163765-44-4,(R)-1-Boc-3-Methylpiperazine,as a common compound, the synthetic route is as follows.

The (R) – 1-BOC-3-methyl-piperazine (300 mg, 1 . 5mmol) dissolved in acetonitrile (10 ml) in, adding DIEA (390 mg, 3mmol) and cyclopropyl methyl bromide (235 mg, 1 . 73mmol), 40 C reaction 2d, cessation of the reaction, the reaction liquid concentrated, column chromatography (DCM: the MeOH=40 […] 1) obtaining white semi-solid 320 mg, yield 84.2%., 163765-44-4

The synthetic route of 163765-44-4 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Institute Of Materia Medica Chinese Academy Of Medical Sciences; Xu, Bailing; Chen, Xiaoguang; Yao, Haiping; Ji, Ming; Jin, Jing; Zhou, Jie; Wang, Ke; Zhao, Dalong; (55 pag.)CN105461697; (2016); A;,
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.278788-60-6,(R)-1-Boc-Piperazine-2-carboxylic acid,as a common compound, the synthetic route is as follows.

Trimethylsilyl diazomethane (2M in hexane, 14 ml) was added dropwise to a solution of (2R)-L-(TERT-BUTOXYVARBONYL) piperazine-2-carboxylic acid (5 g) in methanol (100 ml) and DCM (115 ml), and the solution stirred at room temperature for 16 hours. The solvent was concentrated in vacuo and the residue purified by chromatography, eluting with ethyl acetate then 5% methanol / 7N ammonia in ethyl acetate, to give 1-tert-butyl 2-methyl (2R)- PIPERAZINE-1, 2-dicarboxylate as an oil (2.55 g, 48%); NMR spectrum (DMSO-d6) 1.40 (s, 9H), 2.10 (bs, 1H), 2.52 (m, 1H), 2.72 (dd, 1H), 2.82 (d, 1H), 2.97 (m, 1H), 3.29 (d, 1H), 3.61 (d, 1H), 3.67 (s, 3H), 4.43 (m, 1H) ; Mass spectrum MH+ 245., 278788-60-6

278788-60-6 (R)-1-Boc-Piperazine-2-carboxylic acid 24820285, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2005/26152; (2005); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

154590-35-9, tert-Butyl 4-(4-amino-2-fluorophenyl)piperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Cool in ice a solution of the product of Preparation 17, Step 3 (1.53 g, 5.2 mmol) and DIPEA (1.10 ml, 6.2 mmol) in THF (40 ml). Add dropwise 4-bromobutyryl chloride (1.01 g, 5.4 mmol). Stir 2 h and partition with ether and satd. NaHCO3. Dry (MgSO4) and concentrate to obtain the carbamate as a yellow solid.

154590-35-9, The synthetic route of 154590-35-9 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Schering Corporation; US2005/239795; (2005); 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.278788-66-2,(R)-tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

278788-66-2, To a solution of tert-butyl (3R)-3-(hydroxymethyl)piperazine-1-carboxylate (80.0 g, 370 mmol, 1.0 eq) in Ethyl acetate (1400 mL) was added NaHCO 3 (93.2 g, 1.11 mol, 43.2 mL, 3.0 eq), H 2O (700 mL) and benzyl carbonochloridate (82.0 g, 481 mmol, 68.4 mL, 1.30 eq). The mixture was stirred at 25° C. for 12 hour. After completion, the organic phase was separated, washed with water (500 mL 2) dried over Na 2SO 4 and filtered. The solvent was removed under vacuum to give a residue. The residue was purified by column chromatography (SiO 2, Petroleum ether/Ethyl acetate=40/1 to 1/1). The product 1-benzyl 4-tert-butyl (2R)-2-(hydroxymethyl)piperazine-1,4-dicarboxylate (85.0 g, 235 mmol, 64% yield, 96% purity) was obtained as a yellow oil. LCMS [ESI, M-99]: 251.

As the paragraph descriping shows that 278788-66-2 is playing an increasingly important role.

Reference：
Patent; Mirati Therapeutics, Inc.; Array BioPharma Inc.; Blake, James F.; Burgess, Laurence E.; Chicarelli, Mark Joseph; Christensen, James Gail; Cook, Adam; Fell, Jay Bradford; Fischer, John P.; Marx, Matthew Arnold; Mejia, Macedonio J.; Savechenkov, Pavel; Vigers, Guy P.A.; Smith, Christopher Ronald; Rodriguez, Martha E.; US2019/144444; (2019); 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.1214196-85-6,1-(tert-Butoxycarbonyl)piperazine-2-carboxylic acid,as a common compound, the synthetic route is as follows.

A mixture of 1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid (23 g, 100 mmol) in THF (200 mL) was added NaOH (1 mol/L in H2O, 200 mL, 200 mmol), followed by added Cbz-Cl (19 g, 110 mmol) dropwise. The mixture was stirred at 25 C. for 4 hours. HCl (1N in H2O) was added to pH=5, the organic phase was washed with H2O, brine, dried and evaporated to afford product as yellow oil (25 g, 69%). MS (ESI): mass calcd. for C18H24N2O6 364.16, m/z found 365.1 [M+H]+., 1214196-85-6

The synthetic route of 1214196-85-6 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; VenatoRx Pharmaceuticals, Inc.; BURNS, Christopher J.; COBURN, Glen; LIU, Bin; YAO, Jiangchao; BENETATOS, Christopher; BOYD, Steven A.; CONDON, Stephen M.; HAIMOWITZ, Thomas; US2019/375708; (2019); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

169447-70-5, (S)-tert-Butyl 2-methylpiperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

A mixture of 5 -chloro- 1 -methyl-4-nitro- 1H-pyrazole (1 .00 g, 6.21 mmol), (S)-tertbutyl-2-methylpiperazine- 1 -carboxylate (1.86 g, 9.32 mmol), DIPEA (2.40 g, 18.6 mmol) in EtOH (20 mL) was microwave irradiated for 3 h at 130 C. The reaction mixture was then cooled down, concentrated, and purified by chromatography (silica, PE/EtOAc = 10/1 to 5/1) to afford (S)-tertbutyl-2-methyl-4-( 1 -methyl-4-nitro- 1H-pyrazol-5 -yl)piperazine- 1 -carboxylate (1 .92 g, 5.90 mmol, 95%) as a yellow oil. ESI-MS (EI, m/z): 326.0 [M+H].

169447-70-5, The synthetic route of 169447-70-5 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; NAVITOR PHARMACEUTICALS, INC.; O’NEILL, David John; SAIAH, Eddine; KANG, Seong Woo Anthony; BREARLEY, Andrew; BENTLEY, Jonathan; (565 pag.)WO2018/89433; (2018); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics