Category: 169447-70-5

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

6.1. Example 1(S)-N-(3-bromo-4-fluorophenyl)-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboxamide The captioned compound was prepared in several steps.A. Preparation of (S)-tert-butyl 2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboxylate. (S)-tert-butyl 2-methylpiperazine-1-carboxylate (3 g, 15 mmol), N,N-diisopropylethylamine (3 ml), and 4-chloro-5-methyl-7H-pyrrolo[2,3-d]pyrimidine (2 g, 12 mmol) were added to isopropanol (10 ml). The solution was heated at 120 C. in a sealed pressure tube for 12 hours. The reaction was concentrated under vacuum, and the residue was purified by flash chromatography (80 g SiO2, 0-5% MeOH: CH2Cl2, 50 min) to give clean (S)-tert-butyl 2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboxylate (1.5 g, 4.5 mmol, 38%).1H NMR (400 MHz, chloroform-d) delta ppm 10.42 (br. s., 1H), 8.39 (s, 1H), 6.96 (s, 1H), 4.40 (d, J=6.06 Hz, 1H), 3.83-4.01 (m, 2H), 3.43 (td, J=12.57, 3.41 Hz, 1H), 3.32 (dd, J=12.76, 3.92 Hz, 1H), 3.07 (td, J=12.32, 3.41 Hz, 1H), 2.44 (s, 3H), 1.50 (s, 9H), 1.24 (d, J=6.82 Hz, 3H); MS (ES+) [M+H]+=332.

169447-70-5, As the paragraph descriping shows that 169447-70-5 is playing an increasingly important role.

Reference：
Patent; Harrison, Bryce Alden; Kimball, Spencer David; Mabon, Ross; Rawlins, David Brent; Rice, Dennis S.; Voronkov, Michael Victor; Zhang, Yulian; US2009/42893; (2009); 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

6-Chloropyridine-2-carbonitrile (250 mg, 1.8 mmol) and tert-butyl (2S)-2- methylpiperazine-1-carboxylate (433 mg, 2.17 mmol) were added to a reaction tube with DIPEA (377 pi, 2.17 mmol) in DMF (2.5 ml). The tube was then sealed and the reaction stirred at 80 C for 20 hours. The reaction mixture was concentrated in vacuo and the residue was partitioned between EtOAc (25 ml) and sat aq NaHCO3 (25 ml). The organics were separated and the aqueous phase extracted with EtOAc (2 x 20 ml). The combined organics were washed with water (20 ml), brine (20 ml), dried over MgSO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified via flash column chromatography (gradient of 0 – 100% EtOAc in heptane followed by 0-100% MeOH in EtOAc). The product-containing fractions were combined and concentrated in vacuo to give the title compound as a yellow oil (321 mg, 51 %).1HNMR(500 MHz, Chloroform-d) 7.51 (dd, J = 8.8, 7.2 Hz, 1H), 6.96 (d, J = 7.1 Hz, 1H), 6.76 (d, J = 8.8 Hz, 1H), 4.32 (s, 1H), 4.11 (s, 1H), 4.03 -3.88 (m, 2H), 3.36-3.19 (m, 2H), 3.11 – 2.98 (m, 1H), 1.48 (s,9H), 1.17 (d, J = 6.7 Hz, 3H).LCMS Method 2 – Tr = 1.23 mm (ES+) (M+H)+ 288.0, 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

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.169447-70-5,(S)-tert-Butyl 2-methylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

To a stirred solution of 1 ,1-dimethylethyl (2S)-2-methyl-1-piperazinecarboxylate (0.2g, 1 mmol) in DCM (5mL) was added triethylamine (0.35ml_) and 4- chlorobenzenesulphonyl chloride (0.42g, 2mmol). The mixture was stirred overnight at ambient temperature under argon. To the reaction was added 4- chlorobenzenesulfonyl chloride (0.2g, 0.95mmol) and the reaction stirred for a further 2 hours. The solvent was evaporated and the crude taken up in DCM (25ml_). To the solution was added PS-trisamine (3g) and the mixture stirred at room temperature for 2hours. To the mixture was then added PS-isocyanate (1.5g) and the mixture stirred for a further 30minut.es. The reaction was filtered and the solvent removed by evaporation. The crude product was taken up in DCM, washed twice with water (2 x 5OmL), dried (MgSO4) and filtered. The solvent was evaporated to yield crude product which was dried at 4O0C under vacuum for 1 hour to yield the title compound as an off-white solid (0.284g, 76%).1H NMR (CDCI3) 51.27 (3H, d, J=I), 1.42 (9H, s), 2.24 (1 H, m), 2.42 (1 H, dd, J=11 ,4), 3.16 (1 H, m), 3.49 (1 H, dt, J=11 , 2), 3.67 (1 H, m), 3.93 (1 H, m), 4.34 (1 H, br s), 7.52 (2H, m), 7.67 (2H, m)., 169447-70-5

Big data shows that 169447-70-5 is playing an increasingly important role.

Reference：
Patent; GLAXO GROUP LIMITED; BESWICK, Paul, John; CAMPBELL, Alister; CRIDLAND, Andrew; GLEAVE, Robert, James; PAGE, Lee, William; WO2010/102663; (2010); 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 4-bromo-l,2-difluorobenzene (1 g, 5.18 mmol), (S)-tert-buty 2- methylpiperazine-l-carboxylate (1.04 g, 5.18 mmol), t-BuONa (747 mg, 7.77 mmol), BINAP (40 mg, 0.06 mmol) and Pd2(dba)3 (20 mg, 0.02 mmol) in toluene (15 mL) was stirred at 80C for 3 hrs. The mixture was then purified by chromatography (silica, EtOAc/PE = 1/8) to afford {S)-tert- butyl-4-(3,4-difluorophenyl)-2-methylpiperazine-l-carboxylate (921 mg, 2.95 mmol, 57%) as product. ESI-MS (EI+, m/z): 257.1 [M-55]+., 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; (184 pag.)WO2018/89493; (2018); 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 4-bromo-l,2-difluorobenzene (1 g, 5.18 mmol), (S)-tert-buty 2- methylpiperazine-l-carboxylate (1.04 g, 5.18 mmol), t-BuONa (747 mg, 7.77 mmol), BINAP (40 mg, 0.06 mmol) and Pd2(dba)3 (20 mg, 0.02 mmol) in toluene (15 mL) was stirred at 80C for 3 hrs. The mixture was then purified by chromatography (silica, EtOAc/PE = 1/8) to afford {S)-tert- butyl-4-(3,4-difluorophenyl)-2-methylpiperazine-l-carboxylate (921 mg, 2.95 mmol, 57%) as product. ESI-MS (EI+, m/z): 257.1 [M-55]+., 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; (184 pag.)WO2018/89493; (2018); 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

To 1 ,1-dimethylethyl (2S)-2-methyl-1-piperazinecarboxylate (1g) in DCM (5OmL) was added DIPEA (1.74ml_). 4-cyanobenzenesulfonyl chloride (1.1g) was then added slowly and the reaction mixture was stirred for 1 hour. To the reaction was added DCM (5OmL) and the solution was washed with saturated sodium bicarbonate solution and water. The organic layer was collected and evaporated to dryness under vacuum. The resulting oil was dissolved in 1 ,4-dioxane (1OmL) before the addition of 4M HCI in 1 ,4-dioxane (1OmL) and a few drops of water. The reaction was stirred for 1.5 hours. The reaction mixture was evaporated to dryness under vacuum then dissolved in MeOH. The MeOH solution was loaded onto a 1Og SCX column. The loaded column was then washed with 2 column volumes of MeOH and the desired product was eluted from the column with 1 M ammonia in MeOH. The fraction containing eluted product was evaporated to dryness under vacuum to yield the title compound as a yellow oil (895mg, 68%).MS ES+ve m/z 265 (M+H)

169447-70-5, As the paragraph descriping shows that 169447-70-5 is playing an increasingly important role.

Reference：
Patent; GLAXO GROUP LIMITED; BESWICK, Paul, John; CAMPBELL, Alister; CRIDLAND, Andrew; GLEAVE, Robert, James; PAGE, Lee, William; WO2010/102663; (2010); 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

To 1 ,1-dimethylethyl (2S)-2-methyl-1-piperazinecarboxylate (1g) in DCM (5OmL) was added DIPEA (1.74ml_). 4-cyanobenzenesulfonyl chloride (1.1g) was then added slowly and the reaction mixture was stirred for 1 hour. To the reaction was added DCM (5OmL) and the solution was washed with saturated sodium bicarbonate solution and water. The organic layer was collected and evaporated to dryness under vacuum. The resulting oil was dissolved in 1 ,4-dioxane (1OmL) before the addition of 4M HCI in 1 ,4-dioxane (1OmL) and a few drops of water. The reaction was stirred for 1.5 hours. The reaction mixture was evaporated to dryness under vacuum then dissolved in MeOH. The MeOH solution was loaded onto a 1Og SCX column. The loaded column was then washed with 2 column volumes of MeOH and the desired product was eluted from the column with 1 M ammonia in MeOH. The fraction containing eluted product was evaporated to dryness under vacuum to yield the title compound as a yellow oil (895mg, 68%).MS ES+ve m/z 265 (M+H)

169447-70-5, As the paragraph descriping shows that 169447-70-5 is playing an increasingly important role.

Reference：
Patent; GLAXO GROUP LIMITED; BESWICK, Paul, John; CAMPBELL, Alister; CRIDLAND, Andrew; GLEAVE, Robert, James; PAGE, Lee, William; WO2010/102663; (2010); 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) Step 1 The 7-(bromomethyl)-6-methoxybenzofuran-3(2H)-one (0.514 g, 2.00 mmol) described in [WO2011/136319] and potassium carbonate (0.276 g, 2.00 mmol) were added to 8 mL of methylene chloride and stirred at room temperature. Two milliliters of a methylene chloride solution of tert-butyl (S)-2-methylpiperazine-1-carboxylate (0.401 g, 2.00 mmol) was added dropwise, and stirring was continued for 24 hours at room temperature. The reaction solution was filtered, and the residue obtained by concentrating the filtrate was purified by silica gel chromatography (ethyl acetate/hexane) to obtain tert-butyl (S)-4-[(6-methoxy-3-oxo-2,3-dihydrobenzofuran-7-yl)methyl]-2-methylpiperazine-1-carboxylate (0.531 g, 70%). 1H NMR (300 MHz, CDCl3) delta 1.12 (d, J=6.6 Hz, 3H), 1.36 (s, 9H), 1.98 (dt, J=0.6, 11.7 Hz, 1H), 2.17 (dd, J=4.2, 10.8 Hz, 1H), 2.57 (d, J=10.8 Hz, 1H), 2.72 (d, J=10.8 Hz, 1H), 2.97 (dt, J=3.9, 12.3 Hz, 1H), 3.60 (d, J=2.4 Hz, 2H), 3.69 (d, J=12.3 Hz, 1H), 3.85 (s, 3H), 4.09-4.14 (m, 1H), 4.55 (s, 2H), 6.62 (d, J=8.7 Hz, 1H), 7.54 (d, J=8.7 Hz, 1H).

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

Reference：
Patent; THE UNIVERSITY OF TOKYO; NAGANO, Tetsuo; NAKANO, Hirofumi; HASEGAWA, Tsukasa; SAITO, Nae; KOJIMA, Hirotatsu; OKABE, Takayoshi; MUKAIDA, Naofumi; (42 pag.)US2017/145005; (2017); 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) Step 1 The 7-(bromomethyl)-6-methoxybenzofuran-3(2H)-one (0.514 g, 2.00 mmol) described in [WO2011/136319] and potassium carbonate (0.276 g, 2.00 mmol) were added to 8 mL of methylene chloride and stirred at room temperature. Two milliliters of a methylene chloride solution of tert-butyl (S)-2-methylpiperazine-1-carboxylate (0.401 g, 2.00 mmol) was added dropwise, and stirring was continued for 24 hours at room temperature. The reaction solution was filtered, and the residue obtained by concentrating the filtrate was purified by silica gel chromatography (ethyl acetate/hexane) to obtain tert-butyl (S)-4-[(6-methoxy-3-oxo-2,3-dihydrobenzofuran-7-yl)methyl]-2-methylpiperazine-1-carboxylate (0.531 g, 70%). 1H NMR (300 MHz, CDCl3) delta 1.12 (d, J=6.6 Hz, 3H), 1.36 (s, 9H), 1.98 (dt, J=0.6, 11.7 Hz, 1H), 2.17 (dd, J=4.2, 10.8 Hz, 1H), 2.57 (d, J=10.8 Hz, 1H), 2.72 (d, J=10.8 Hz, 1H), 2.97 (dt, J=3.9, 12.3 Hz, 1H), 3.60 (d, J=2.4 Hz, 2H), 3.69 (d, J=12.3 Hz, 1H), 3.85 (s, 3H), 4.09-4.14 (m, 1H), 4.55 (s, 2H), 6.62 (d, J=8.7 Hz, 1H), 7.54 (d, J=8.7 Hz, 1H).

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

Reference：
Patent; THE UNIVERSITY OF TOKYO; NAGANO, Tetsuo; NAKANO, Hirofumi; HASEGAWA, Tsukasa; SAITO, Nae; KOJIMA, Hirotatsu; OKABE, Takayoshi; MUKAIDA, Naofumi; (42 pag.)US2017/145005; (2017); 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

To 1 ,1-dimethylethyl (2S)-2-methyl-1-piperazinecarboxylate (1g) in DCM (5OmL) was added DIPEA (1.74ml_). 4-cyanobenzenesulfonyl chloride (1.1g) was then added slowly and the reaction mixture was stirred for 1 hour. To the reaction was added DCM (5OmL) and the solution was washed with saturated sodium bicarbonate solution and water. The organic layer was collected and evaporated to dryness under vacuum. The resulting oil was dissolved in 1 ,4-dioxane (1OmL) before the addition of 4M HCI in 1 ,4-dioxane (1OmL) and a few drops of water. The reaction was stirred for 1.5 hours. The reaction mixture was evaporated to dryness under vacuum then dissolved in MeOH. The MeOH solution was loaded onto a 1Og SCX column. The loaded column was then washed with 2 column volumes of MeOH and the desired product was eluted from the column with 1 M ammonia in MeOH. The fraction containing eluted product was evaporated to dryness under vacuum to yield the title compound as a yellow oil (895mg, 68%).MS ES+ve m/z 265 (M+H)

169447-70-5, As the paragraph descriping shows that 169447-70-5 is playing an increasingly important role.

Reference：
Patent; GLAXO GROUP LIMITED; BESWICK, Paul, John; CAMPBELL, Alister; CRIDLAND, Andrew; GLEAVE, Robert, James; PAGE, Lee, William; WO2010/102663; (2010); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics