Category: 74879-18-8

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.74879-18-8,(S)-(+)-2-Methylpiperazine,as a common compound, the synthetic route is as follows.

In a sealed tube, 2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-7-fluoro-pyrido[1,2-a]pyrimidin-4-one (Intermediate 2; 33 mg, 0.107 mmol), and (S)-2-methylpiperazine (43 mg, 0.427 mmol, 4.0 eq.) were stirred in DMSO (2 mL) at 120 C. overnight. The solvent was removed under high vacuum. The residue was taken up in CH2Cl2 and washed with an aqueous saturated solution of NaHCO3. The organic layer was separated and dried over Na2SO4 and concentrated in vacuo. The crude was purified by column chromatography (SiO2, CH2Cl2/MeOH=95/5 to 90/10) to afford the title product (18 mg, 43%) as a light yellow solid. MS m/z 390.3 [M+H+]., 74879-18-8

The synthetic route of 74879-18-8 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Hoffmann-La Roche Inc.; PTC Therapeutics, Inc.; Ratni, Hasane; Green, Luke; Weetall, Maria L.; Naryshkin, Nikolai A.; (33 pag.)US2019/315773; (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.74879-18-8,(S)-(+)-2-Methylpiperazine,as a common compound, the synthetic route is as follows.

In a sealed tube, 2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-7-fluoro-pyrido[1,2-a]pyrimidin-4-one (Intermediate 2; 33 mg, 0.107 mmol), and (S)-2-methylpiperazine (43 mg, 0.427 mmol, 4.0 eq.) were stirred in DMSO (2 mL) at 120 C. overnight. The solvent was removed under high vacuum. The residue was taken up in CH2Cl2 and washed with an aqueous saturated solution of NaHCO3. The organic layer was separated and dried over Na2SO4 and concentrated in vacuo. The crude was purified by column chromatography (SiO2, CH2Cl2/MeOH=95/5 to 90/10) to afford the title product (18 mg, 43%) as a light yellow solid. MS m/z 390.3 [M+H+]., 74879-18-8

The synthetic route of 74879-18-8 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Hoffmann-La Roche Inc.; PTC Therapeutics, Inc.; Ratni, Hasane; Green, Luke; Weetall, Maria L.; Naryshkin, Nikolai A.; (33 pag.)US2019/315773; (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.74879-18-8,(S)-(+)-2-Methylpiperazine,as a common compound, the synthetic route is as follows.,74879-18-8

To a solution of (S)-2-methylpiperazine (10 g, 100 mmol, eq) in EtOH (200 ml_) was added DIPEA (43.58 ml_, 250 mmol, 2.5 eq) and BOC20 (21.8 ml_, 100 mmol, 1 eq) at RT, then the reaction mixture was continued for 16 h. TLC analysis indicated formation of a less polar spot. The reaction mixture was concentrated to crude compound, which was diluted with water and extracted with EtOAc (3×100 ml_). The combined organic layer was dried over Na2S04 then concentrated to give (S)-tert-butyl 3-methylpiperazine- 1 -carboxylate (18 g, 90%) as a colorless oil.

As the paragraph descriping shows that 74879-18-8 is playing an increasingly important role.

Reference：
Patent; ONTARIO INSTITUTE FOR CANCER RESEARCH (OICR); AL-AWAR, Rima; ISAAC, Methvin; CHAU, Anh My; MAMAI, Ahmed; WATSON, Iain; PODA, Gennady; SUBRAMANIAN, Pandiaraju; WILSON, Brian; UEHLING, David; (191 pag.)WO2019/119145; (2019); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

74879-18-8, (S)-(+)-2-Methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

EXAMPLE 25A (3S)-3-methyl-1-pyridin-2-ylpiperazine (S)-(+)-2-Methylpiperazine (0.50 g, 0.005 mol, Aldrich) and 2-bromopyridine (5 mL, 0.05 mol) were combined and heated at 120 C. for 14 hours. The reaction mixture was allowed to cool to 23 C. and partitioned between ethyl acetate and water. The layers were separated, and the water layer extracted twice with ethyl acetate. The aqueous phase was brought to pH ~11 with a solution of saturated sodium bicarbonate and solid sodium carbonate. Sodium chloride was added, and the saturated aqueous solution was extracted with ethyl acetate (2*) and dichloromethane (2*). The combined organic extracts were dried over Na2SO4, filtered, and the filtrate concentrated under reduced pressure to afford 0.6 g (67% yield) of the title compound. 1H NMR (400 MHz, DMSO-d6) delta1.02 (d, J=6.0 Hz, 3H), 2.27 (dd, J=10, 12 Hz, 1), 2.67 (m, 3H), 2.92 (m, 1H), 4.07 (m, 2H), 6.58 (dd, J=6, 8 Hz, 1H), 6.77 (d, J=8 Hz, 1H), 7.49 (m, 1H), 8.08 (m, 1H); MS (ESI) m/e 178 (M+H)+., 74879-18-8

74879-18-8 (S)-(+)-2-Methylpiperazine 2734219, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; Cowart, Marlon D.; Bhatia, Pramila A.; Daanen, Jerome F.; Stewart, Andrew O.; Patel, Meena V.; Kolasa, Teodozyj; Brioni, Jorge D.; Rohde, Jeffrey; US2002/169167; (2002); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

74879-18-8, (S)-(+)-2-Methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated,74879-18-8

In a sealed tube, 7-fluoro-2-(2-methyl-[l,2,4]triazolo[l,5-a]pyrimidin-6-yl)-4H-pyrido[l,2- a]pyrimidin-4-one (Intermediate (VT1), 30 mg, 0.101 mmol), (S)-2-methylpiperazine (30.4 mg, 0.304 mmol, 3 eq.) and TEA (51.2 mg, 70.6 mu, 0.506 mmol, 5 eq.) were dissolved in DMSO (2 ml). The reaction mixture was heated at 120 C for 12 hours. The crude was filtered to afford the title product (29 mg, 77%) as a yellow solid. MS m/z 377.2 [M+H]+.

The synthetic route of 74879-18-8 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; GILLESPIE, Robert Jack; HASANE, Ratni; SARIE, Jerome Charles; (89 pag.)WO2016/184832; (2016); 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.74879-18-8,(S)-(+)-2-Methylpiperazine,as a common compound, the synthetic route is as follows.

Example 15 A 2-liter four-neck flask with a thermometer, condenser and stirrer was charged with 200.4 g (= 2.00 moles) of racemic 2-methylpiperazine, 280.0 g of water and 96.0 g of methanol for perfect dissolution. Then, 300.4 g of 50 wt% D-tartaric acid aqueous solution (150.2 g = 1.000 mole of D-tartaric acid) was added at 40 to 45C, and the temperature was further raised up to 72C, being followed by addition of 120.2 g (= 2.00 moles) of acetic acid and aging at the temperature for 2 hours. The solvent composition was water/methanol = 81.8/18.2 (ratio by weight), and the amount of the solvent based on the racemic 2-methylpiperazine was 2.63 times by weight. Then, cooling was carried out down to 25C, taking 12 hours, and precipitated crystals were collected by filtration. The obtained crystals were dried in vacuum, to obtain 214.8 g (= 0.858 mole) of a diastereomer salt. The optical purity of the salt was 93.9%ee, and the yield of the S-isomer in the obtained salt based on the amount of the S-isomer in the supplied (+/-)-2-methylpiperazine was 83.2%. Subsequently, a 1-liter flask was charged with 380 g of water, and the obtained 214.8 g of crystals {pure (S)-2-methylpiperazine content = 83.4 g} were added. Perfect dissolution was achieved at 80 to 85C, and cooling was carried out down to 15C, taking 12 hours. Precipitated crystals were collected by filtration and dried in vacuum to obtain 187.2 g of a salt. Its optical purity was 99.4%ee, and the yield of the S-isomer in the obtained salt based on the amount of (S)-2-methylpiperazine in the supplied crystals was 89.8%. A 500 ml four-neck flask with a thermometer, condenser and stirrer was charged with 150 g of water, and 185.0 g of (S)-2-methylpiperazine D-tartaric acid salt (= 0.739 mole, optical purity of 2-methylpiperazine = 99.4%ee) obtained before and 69.1 g (= 0.863 mole) of 95% pure calcium hydroxide were added. The slurry was heated up to 70 to 80C, and stirred for 3 hours, then being cooled to room temperature. Subsequently, the non-dissolved salt was filtered away, to obtain the mother liquor. The mother liquor was GC-analyzed, and as a result, it was found that 68.7 g (= 0.686 mole) of optically active 2-methylpiperazine existed in the mother liquor (yield 92.8%). Furthermore, as a result of HPLC analysis, the optical purity of (S)-2-methylpiperazine was 99.4%ee. Then, water was distilled away till about 50 wt% was reached, being followed by addition of 1-butanol, and azeotropic dehydration was carried out till the water content of the system became less than 1 wt%. In a 1-liter four-neck flask, 50.0 g of the (S)-2-methylpiperazine (= 0.499 mole, optical purity 99.4%ee) obtained before was placed, and 440 g of 1-butanol was added for dissolution. The solution was cooled down to 0C, and 92.5 g (= 0.534 mole) of benzyl chlorocarbonate was added dropwise with the liquid temperature kept in a range from 0 to 8C. Then, stirring was carried out at 0C for 2 hours, and 300 g of 1-butanol was distilled away under reduced pressure, being followed by addition of 300 g of water. Subsequently 35% hydrochloric acid water was used to adjust the pH to 1.0, and 220 g of toluene was added, being followed by stirring for 30 minutes. The upper layer was then removed, and the same amount of toluene was added again. The same operation was repeated to carry out washing operation. Subsequently 48% sodium hydroxide aqueous solution was used to adjust the pH of the reaction solution to 12.1. In this case, white turbidity occurred due to liberated 1-benzyloxycarbonyl-3-methylpiperazine. To the white turbid solution, 400 g of toluene was added, and stirring water carried out for 30 minutes. The lower layer was then removed, and the upper layer was concentrated under reduced pressure at 60 to 70C in temperature. Subsequently toluene was distilled away to obtain 88.5 g of a concentrate. Eighty five point .zero grams of the obtained 1-benzyoxycarbonyl-3-methylpiperazine was fed to a thin film distiller (heating surface area 0.02 m2) using a liquid feed pump at 0.6 liter/h. The temperature of the heating medium was 150C, and a low-boiling component was cut at a vacuum degree of 360 Pa, to obtain 82.8 g of a liquid remaining in the distiller. The liquid remaining in the distiller was again fed to the same thin film distiller at 0.6 liter/h using a liquid feed pump. The temperature of the heating medium was 220C, and product distillation was carried out at 87 to 116 Pa in vacuum degree, to obtain 76.1 g of a distillate. The obtained compound was analyzed. As a result, the intended 1-benzyloxycarbonyl-3-methylpiperazine accounted for 99.4 liquid chromatography area %. The impurities showed 0.25 liquid chromatography area % for benzyl alcohol, 0.03 liquid chromatography area % for 1-benzyl-4-benzyloxycarbonyl-2-methylpiperazine, 0.02 liquid chromatography area % for 1-benzyl-2-methylpiperazine and no detection for 1,4-dibenzyloxycarbonyl-2-methylpiperazine (and 0.08 area % for sol…, 74879-18-8

As the paragraph descriping shows that 74879-18-8 is playing an increasingly important role.

Reference£º
Patent; Toray Fine Chemicals Co., Ltd.; EP1548010; (2005); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

74879-18-8, (S)-(+)-2-Methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated,74879-18-8

Triethylamine (2.85 ml) was added to a solution of (S)-2-methyl piperazine (1 g) in methanol (25 ml) followed by portion wise addition of BOC anhydride (2.18 g). The reaction mixture was stirred for 17 h, concentrated in vacuo. The residue was partitioned between water and ethyl acetate. The organic phase was dried (MgSO4), and then concentrated in vacuo. The residue was purified by chromatography (silica, ethyl acetate as eluent, then 90:10:1 mixture of ethyl acetate: methanol: ammonia) to give the sub-title compound (1.3 g). 1H NMR (CDCl3) delta 4.03-3.85 (2H, m), 2.95 (IH, d), 2.86-2.65 (3H, m), 2.5-2.3 (IH, m), 1.48 (9H, s) and 1.05 (3H, d).

The synthetic route of 74879-18-8 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2006/56752; (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.74879-18-8,(S)-(+)-2-Methylpiperazine,as a common compound, the synthetic route is as follows.,74879-18-8

In a sealed tube, 7-fluoro-9-methyl-2-(2-methylimidazo[l,2-b]pyridazin-6-yl)pyrido[l,2- a]pyrimidin-4-one (Intermediate 3; 250 mg, 0.808 mmol), and (S)-2-methylpiperazine (405 mg, 4.04 mmol, 5.0 eq.) were stirred in DMSO (6 mL) and heated at 130C overnight. The solvent was removed under high vacuum. The residue was taken up in CH2C12and washed with an aqueous saturated solution of NaHC03. The organic layer was separated and dried over Na2S04and concentrated in vacuo. The crude was purified by column chromatography (Si02,CH2Cl2/MeOH=95/5 to 85/15) to afford the title product (135 mg, 43%) as a light yellow solid. MS m/z 390.3 [M+H+].

As the paragraph descriping shows that 74879-18-8 is playing an increasingly important role.

Reference£º
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; MCCARTHY, Kathleen Dorothy; METZGER, Friedrich; RATNI, Hasane; (76 pag.)WO2017/81111; (2017); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

74879-18-8, (S)-(+)-2-Methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated,74879-18-8

(S)+-2-methylpiperazine (10 g) was dissolved in acetonitrile (140 ml) and cooled to 5-10 C. whereupon triethylamine (35 ml) was added, followed by drop wise addition of a solution of trityl chloride (27.9 g) in DCM (80 ml). The reaction was stirred for 1 h at RT. The resulting slurry was cooled to approximately 0 C. then filtered. The filtrate was evaporated in vacuo and the residue was purified by chromatography (silica, 0-1% MeOH/DCM as eluent), then triturated with ether to give the sub-title compound as a white solid yield, 29.8 g.1H NMR CDCl3: delta 7.49-7.37 (6H, m), 7.26 (6H, t), 7.15 (3H, t), 3.38-3.28 (1H, m), 3.22 (1H, dd), 3.11-2.99 (3H, m), 1.74-1.6 (1H, m), 1.44-1.3 (1H, m), 1.11 (3H, d).

The synthetic route of 74879-18-8 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; ASTRAZENECA AB; US2008/255150; (2008); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

74879-18-8, (S)-(+)-2-Methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

In a sealed tube, 2- (2, 8-dimethylimidazo [1 ,2-b]pyridazin-6-yl)-7-fluoro-9-methyl- pyrido[1,2-a]pyrimidin-4-one (Intermediate 4; 50 mg, 0.155 mmol) and (S)-2-methylpiperazine (62 mg, 0.6 19 mmol, 4.0 eq.) were stuffed in DMSO (2 mL) at 125C overnight. The solvent was removed under high vacuum. The residue was taken up in CH2C12 and washed with an aqueoussaturated solution of NaHCO3. The organic layer was separated and dried over Na2SO4 and concentrated in vacuo. The crude was purified by column chromatography (Si02, CH2C12/MeOH=95/5 to 90/10) to afford the title product (45 mg, 72%) as a light yellow solid. MS m/z 404.3 [M+Hi., 74879-18-8

74879-18-8 (S)-(+)-2-Methylpiperazine 2734219, apiperazines compound, is more and more widely used in various fields.

Reference£º
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; ALSENZ, Jochem; GRASSMANN, Olaf; KUEHL, Peter; METZGER, Friedrich; MCCARTHY, Kathleen Dorothy; MORAWSKI VIANNA, Eduardo Paulo; WOODHOUSE, Marvin Lloyd; (130 pag.)WO2017/80967; (2017); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics