Category: 163765-44-4

163765-44-4, (R)-1-Boc-3-Methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Intermediate 34: (2R)-2-methyl-1-(methylsulfonyl)piperazine hydrochloride; To a solution of 1 , 1-dimethylethyl (3R)-3-methyl-1-piperazinecarboxylate(commercially available, for example from Sigma Aldrich, St Louis, USA, 1 .18 g, 4.98 mmol) in NaOH (2 M aqueous) (6.23 ml, 12.5 mmol) and THF (10 ml) at rt was added mesyl chloride (0.408 ml, 5.23 mmol) over 30 seconds. The solution was stirredvigorously at rt for 2 hours. Additional mesyl chloride (0.408 ml, 5.23 mmol) wasadded and the reaction was stirred vigorously at rt for 2 hours. Additional mesyl chloride (0.408 ml, 5.23 mmol) was added and the solution stirred vigorously at rt for 18 hours. The reaction was diluted with ethyl acetate (50 ml), then washed with 2M aqueous HCI (2 x 25 ml), brine (25 ml), dried (MgS04), filtered and concentrated under vacuum to leave a clear oil (900 mg) that became a crystalline white solid on standing overnight. This was redissolved in DCM (5.0 ml), then TFA (1.24 ml, 16.2 mmol) was added and the solution heated at reflux for 2 hours. The solution was cooled to rt, and concentrated under vacuum to leave a pale orange paste. This was re-dissolved in methanol (10 ml) and applied to an SCX-2 cartridge (25 g), washing with MeOH (50 ml). The product was eluted with 2M NH3 in MeOH (50 ml) and the solvent removed under vacuum to leave a viscous clear oil (361 mg). This was re- dissolved in methanol (10 ml) and aqueous HCI (2 M, 2.0 ml, 4.00 mmol) added. Concentration under vacuum, followed by azeotroping with toluene (2 x 25 ml) left a white solid, (2R)-2-methyl-1 -(methylsulfonyl)piperazine hydrochloride (412 mg).1H NMR (400 MHz, DMSO-d6) delta ppm 1 .35 (d, J=7.0 Hz, 3 H), 2 91 (m, 1 H), 3.04 (s, 3 H), 3.06 – 3.21 (m, 3 H), 3.33 (ddd, J=14.5, 12.1 , 2.9 Hz, 1 H), 3.61 (d, J=14. 5 Hz, 1 H), 4.13 (m, 1 H), 9.26 (br s, 1 H), 9.83 (br s, 1 H).

163765-44-4, 163765-44-4 (R)-1-Boc-3-Methylpiperazine 2756811, apiperazines compound, is more and more widely used in various fields.

Reference£º
Patent; CONVERGENCE PHARMACEUTICALS LIMITED; BESWICK, Paul John; GLEAVE, Robert James; HACHISU, Shuji; VILE, Sadie; BERTHELEME, Nicolas; WARD, Simon E; WO2012/4604; (2012); 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.

Example 97′ {3-[6-(6-Methoxy-pyridin-3-yl)-quinazolin-4-yl]-phenyl}-((R)-2-methyl-piperazin-1-yl)-methanone To a stirred solution of 3-[6-(6-methoxy-pyridin-3-yl)-quinazolin-4-yl]-benzoic acid (100 mg, 0.254 mmol) in 2 mL of DMF, was added HBTU (144 mg, 0.381 mmol) and DIPEA (0.177 mL, 1.016 mmol). The reaction mixture was stirred at rt for 30 min, (R)-3-methyl-piperazine-1-carboxylic acid tert-butyl ester (76 mg, 0.381 mmol) was added and the resulting reaction mixture stirred for a further 2 h at rt. The reaction was quenched with H2O, and extracted with CH2Cl2. The organic layer was washed with brine, dried over MgSO4, filtered and evaporated under vacuum. The residue was dissolved in 3 ml of CH2Cl2 and TFA (1 ml) was added. The reaction mixture was stirred at ambient temperature for 2 h. After this period of time, the mixture was concentrated and purified by preparative reverse phase Gilson HPLC and subsequent neutralization of the combined fractions over PL-HCO3 MP gave the title compound (29 mg, 26% yield) as a white powder. 1H-NMR (400 MHz, DMSO-d6, 298 K): delta ppm 1.23 (d, 3H) 2.55-3.2 (m, 7H) 3.91 (s, 3H) 6.95 (d, 1H) 7.62 (d, 1H) 7.72 (t, 1H) 7.81 (s, 1H) 7.98 (d, 1H) 8.11 (d, 1H) 8.22 (d, 2H) 8.38 (d, 1H) 8.59 (s, 1H) 9.38 (s, 1H). MS: 440.1 [M+1]+, Rt(2′)=0.89 min.

163765-44-4, As the paragraph descriping shows that 163765-44-4 is playing an increasingly important role.

Reference£º
Patent; NOVARTIS AG; COOKE, Nigel Graham; FERNANDES GOMES DOS SANTOS, Paulo Antonio; FURET, Pascal; HEBACH, Christina; HOGENAUER, Klemens; HOLLINGWORTH, Gregory; KALIS, Christoph; LEWIS, Ian; SMITH, Alexander Baxter; SOLDERMANN, Nicolas; STAUFFER, Frederic; STRANG, Ross; STOWASSER, Frank; TUFFILLI, Nicola; VON MATT, Anette; WOLF, Romain; ZECRI, Frederic; US2015/342951; (2015); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

163765-44-4, (R)-1-Boc-3-Methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

The compound ferf-butyl (3R)-3-methylpiperazine-1-carboxylate (25g, 124.8 mmol) was dissolved in DMSO (50 mL). To reaction mixture was added 6-chloronicotinonitrile (19 g, 137.3 mmol), K2CO3 (32.7g, EPO 235.9 mmol) and Cu(MeCN)4PF6 (0.42 g, 1.12 mmol) then warmed to 140 0C for 4h. The solution was cooled to 25 0C and diluted with EtOAc (200 mL) then partitioned between aqueous HCI (3 X 50 mL 0.1 N) and saturated aqueous sodium bicarbonate (2 X 50 mL). The organic layer was dried over sodium sulfate, filtered through silica (50 mL) and concentrated. The residue was purified by crystallizing from 20 mL of warm EtOAc after standing for 2h at 25 0C. The mother liquor was decanted, the solid rinsed with EtOAc (2 x 10 mL) and placed under high vacuum for 2h that afforded the title compound 23(0 as a white crystalline solid (32.6 g, 96%). HPLC Rt: 3.444 (95.4%). 1H NMR (400MHz, CDCI3) delta: 8.42 (s, 1 H), 7.63 (dd, J = 9.1 , 2.3 Hz, 1 H), 6.56 (d, J = 9.1 Hz, 1 H), 5.30 (s, 1 H), 4.53 (bs, 1 H), 4.13 (bs, 1 H), 3.94 (bs, 1 H), 3.26-3.21 (m, 2H), 2.99 (bs, 1 H), 1.49 (s, 9H), 1.20 (d, J = 6.8 Hz, 3H). LCMS (ESI): mlz: 303.3., 163765-44-4

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

Reference£º
Patent; PFIZER INC.; WO2006/106423; (2006); A2;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

163765-44-4, (R)-1-Boc-3-Methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Intermediate 10 RRN No.442(R)-tert-Butyl 4-(4-amino-1-methyl-1H-pyrazol-5-yl)-3-methylpiperazine-1-carboxylate [0401] 5-chloro-1-methyl-4-nitro-1H-pyrazole from Example 1 (355 mg, 2.2 mmol) and potassium fluoride (511 mg, 8.8 mmol) in dry DMSO (20 mL) was added (R)-tert-butyl 3-methylpiperazine-1-carboxylate (507 mg, 2.53 mmol) and the mixture was heated in the microwave at 100 C. for 10 hr. The mixture was partitioned between water (40 mL) and EtOAc (100 mL) and the organic layer passed through a phase separation cartridge and concentrated under reduced pressure. Purification via silica gel column chromatography (0-100% EtOAc/isohexane) gave (R)-tert-butyl 3-methyl-4-(1-methyl-4-nitro-1H-pyrazol-5-yl)piperazine-1-carboxylate as an orange gum (627 mg). To a solution of this gum (179 mg, 0.55 mmol) and ammonium formate (256 mg, 4.4 mmol) in MeOH (10 mL) under nitrogen was added 10% palladium on carbon (59 mg, 0.55 mmol). The mixture was heated at 70 C. for 4 hr before being cooled, filtered and concentrated under reduced pressure. The residue was partitioned between water (20 mL) and DCM (60 mL) and the organic layer separated, passed through a phase separation cartridge and concentrated under reduced pressure to give (R)-tert-butyl 4-(4-amino-1-methyl-1H-pyrazol-5-yl)-3-methylpiperazine-1-carboxylate as a brown gum (150 mg, 80% over two steps). LCMS (ES+) m/z 296 (M+1)., 163765-44-4

As the paragraph descriping shows that 163765-44-4 is playing an increasingly important role.

Reference£º
Patent; GENENTECH, INC.; Hodges, Alastair James; Matteucci, Mizio; Sharpe, Andrew; Sun, Minghua; Wang, Xiaojing; Tsui, Vickie H.; US2013/79321; (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.163765-44-4,(R)-1-Boc-3-Methylpiperazine,as a common compound, the synthetic route is as follows.

Example 109a (R)-tert-Butyl 3-Methyl-4-(6-nitropyridin-3-yl)piperazine-1-carboxylate 109a A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and reflux condenser was charged with 1,4-dioxane (60 mL), 5-bromo-2-nitropyridine (2.0 g, 10.0 mmol), (R)-tert-butyl 3-methylpiperazine-1-carboxylate (2.0 g, 10.0 mmol), and cesium carbonate (6.5 g, 20 mmol). See . After bubbling nitrogen through the resulting mixture for 30 minutes, XantPhos (579 mg, 1.0 mmol) and tris(di-benzylideneacetone)dipalladium(0) (915 mg, 1.0 mmol) were added, and the reaction mixture was heated at 100 C. for 15 h. After this time the reaction was cooled to room temperature and filtered. The filtrate was partitioned between ethyl acetate (100 mL) and water (100 mL). The aqueous layer was separated and extracted with ethyl acetate (150 mL*3). The combined organic layer was washed with brine (50 mL) and dried over sodium sulfate. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified on flash column eluting with 30:1 DCM/MeOH to afford 109a (1.6 g, 44%) as a yellow solid. MS: [M+H]+ 323. 1H NMR (500 MHz, DMSO) delta 8.21 (d, J=3.5, 1H), 8.18 (d, J=9.0, 1H), 7.43-7.45 (m, 1H), 4.33 (s, 1H), 3.92-3.99 (m, 1H), 3.80 (d, J=12.5, 2H), 3.06-3.23 (m, 3H), 1.43 (s, 9H), 1.09 (d, J=6.5, 3H).

163765-44-4, 163765-44-4 (R)-1-Boc-3-Methylpiperazine 2756811, apiperazines compound, is more and more widely used in various fields.

Reference£º
Patent; GENENTECH, INC.; Crawford, James John; Young, Wendy B.; US2013/116245; (2013); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

163765-44-4, (R)-1-Boc-3-Methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

General procedure: In a dry sealed tube under argon were placed, to a solution of 1-Boc-piperazine (5.04 mmol), potassium carbonate (13.1 mmol) in acetonitrile (12.6 mL) was added 2,5-dibromo pyrimidine13(5.04 mmol). The mixture was allowed to stir at 80 C for 12 h. After completion of the reaction (monitored by TLC), the mixture was then cooled at room temperature, then it was quenched with saturated aqueous NH4Cl (10 mL) and extracted with EtOAc. The organic layers were dried over anhydrous MgSO4and concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel (EtOAc:n-hexane = 1:8) to afford piperazine11a., 163765-44-4

163765-44-4 (R)-1-Boc-3-Methylpiperazine 2756811, apiperazines compound, is more and more widely used in various fields.

Reference£º
Article; Kim, Juhyeon; Kim, Yoon Jung; Londhe, Ashwini M.; Pae, Ae Nim; Choo, Hyunah; Kim, Hak Joong; Min, Sun-Joon; Molecules; vol. 24; 18; (2019);,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

163765-44-4, (R)-1-Boc-3-Methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

To 188 (15 mg, 0.039 mmol) in DMF (3 mL) was added (5)-l-N- Boc-2-methylpiperazine (9.4 mg, 0.047 mmol) and Et3N (10 mu, 0.072 mmol) and heated at 90 C for 2 h. Solvent was removed under reduced pressure and the residue was purified by preparatory TLC (CH2Cl2:MeOH, 10:1) to afford Boc-protected intermediate in quantitative yield. To this was added 1 mL of a solution of CH2Ci2:TFA (7:3) and stirred at rt for 4 h. Solvent was removed under reduced pressure and the residue was purified by preparatory TLC (CH2Cl2:MeOH-NH3 (7 N), 20: 1) to afford 17 mg (98%) of 191. 1H NMR (500 MHz, CDC13): delta 8.17 (s, 1H), 7.35 (d, J= 8.4 Hz, 2H), 7.10 (t, J= 7.8 Hz, 1H), 7.04 (d, J= 8.4 Hz, 2H), 6.72 (dd, J= 8.1, 1.7, 1H), 6.67 (d, J= 7.5 Hz, 1H), 6.60 (s, 1H), 5.29 (d, J= 12.7 Hz, 1H), 5.24 (d, J = 12.7 Hz, 1H), 4.76 (m, 1H), 4.42-4.47 (m, 1H), 3.65 (s, 3H), 3.00-3.12 (m, 2H), 2.84-2.94 (m, 2H), 2.67-2.73 (m, 1H), 1.22 (d, J= 6.8 Hz, 3H); MS (ESI) m/z [M+H]+ 448.3., 163765-44-4

163765-44-4 (R)-1-Boc-3-Methylpiperazine 2756811, apiperazines compound, is more and more widely used in various fields.

Reference£º
Patent; MEMORIAL SLOAN KETTERING CANCER CENTER; CHIOSIS, Gabriela; KANG, Yanlong; PATEL, Hardik J.; PATEL, Maulik; OCHIANA, Stefan; RODINA, Anna; TALDONE, Tony; SHRESTHA, Liza; (288 pag.)WO2015/175707; (2015); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

163765-44-4, (R)-1-Boc-3-Methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

To a stirred solution of commercially available (R)-3-methyl-piperazine-1-carboxylic acid tert-butyl ester (8.78 g, 44 mmol) in CH2Cl2 (80 mL) at 0 C. were added Et3N (12.15 mL, 88 mmol) and methanesulfonyl chloride (5.09 mL, 66 mmol). Stirring was continued at RT overnight, the reaction was poured onto water and extracted with CH2Cl2. The combined organic phases were dried on Na2SO4 and concentrated under vacuo. The crude product was dissolved in CH2Cl2 (50 mL) and TFA (15 mL) was added. After 2 hours at RT, the volatiles were removed under vacuo, the crude was dissolved in CH2Cl2 and washed with aq. NaHCO3 (until pH=8). The organic phase was dried on Na2SO4 and concentrated under vacuo to yield 2.63 g (34%) of (R)-1-methanesulfonyl-2-methyl-piperazine as a light yellow oil., 163765-44-4

As the paragraph descriping shows that 163765-44-4 is playing an increasingly important role.

Reference£º
Patent; Jablonski, Philippe; Kawasaki, Kenichi; Knust, Henner; Limberg, Anja; Nettekoven, Matthias; Ratni, Hasane; Riemer, Claus; Wu, Xihan; US2009/54644; (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.163765-44-4,(R)-1-Boc-3-Methylpiperazine,as a common compound, the synthetic route is as follows.

Intermediate 3 (2.63 g, 13.1 mmol) was dissolved in DCE (60 mL). Cyclobutanone (1.38 g, 19.7 mmol) and acetic acid (0.75 mL, 13.1 mmol) were added and the mixture stirred at rt for 30 min. NaBH(OAc)3 (4.18 g, 19.7 mmol) was added portionwise and the mixture was stirred at rt overnight. Sat. Na2CO3 (50 mL) was added and the aq. layer was extracted with DCM (3¡Á75 mL). The combined organic phases were dried over Na2SO4, filtered and concentrated under reduced pressure to provide 2.58 g title compound (77%) as an oil. 1H NMR (300 MHz, CDCl3) delta ppm 0.97 (d, J=6.4 Hz, 3H) 1.45 (s, 9H) 1.61-1.70 (m, 2H) 1.81-1.91 (m, 1H) 1.93-2.00 (m, 2H) 2.03-2.14 (m, 2H) 2.41-2.51 (m, 1H) 2.58-2.65 (m, 1H) 2.94-3.05 (m, 1H) 3.06-3.16 (m, 1H) 3.29-3.58 (m, 3H).

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

Reference£º
Patent; ASTRAZENECA AB; US2010/216812; (2010); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics