Category: 438631-77-7

438631-77-7,With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.438631-77-7,(R)-1-tert-Butyl 3-methyl piperazine-1,3-dicarboxylate,as a common compound, the synthetic route is as follows.

To a de-gassed solution of 78 THF (325 ml) and 56 DIPEA (12.74 ml, 73.14 mmol) under a nitrogen atmosphere was added 113 7-bromo-4,6-dichloro-8-fluoro-3-nitroquinoline (26.59 g, 66.49 mmol) and 272 1-(tert-butyl) 3-methyl (R)-piperazine-1,3-dicarboxylate (17.05 g, 69.81 mmol). The resultant brown solution was heated at 61 C. (internal temperature) under a nitrogen atmosphere for 18 hours. Additional DIPEA (5.8 ml, 33.24 mmol) and 1-(tert-butyl) 3-methyl (R)-piperazine-1,3-dicarboxylate (8.12 g, 33.24 mmol) was then added and the resultant reaction mixture was heated at 61 C. (internal) for 4 hours. The reaction mixture was concentrated in vacuo, and the crude product was purified by flash silica chromatography, elution gradient 0 to 50% 57 ethyl acetate in 58 heptane. Pure fractions were evaporated to dryness to afford 273 1-tert-butyl 3-methyl (3R)-4-(7-bromo-6-chloro-8-fluoro-3-nitroquinolin-4-yl)piperazine-1,3-dicarboxylate (32.1 g, 88%) as an orange solid. 1H NMR (400 MHz, DMSO, 30 C.) 1.45 (9H, s), 2.52-2.53 (1H, m), 3.29-3.34 (1H, m), 3.56 (3H, s), 3.61-3.77 (2H, m), 3.78-3.93 (1H, m), 4.04-4.21 (1H, m), 4.33-4.4 (1H, m), 8.36 (1H, d), 9.16 (1H, s). m/z: ES+ [M+H]+ 547. 97% ee.

As the paragraph descriping shows that 438631-77-7 is playing an increasingly important role.

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

438631-77-7,With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.438631-77-7,(R)-1-tert-Butyl 3-methyl piperazine-1,3-dicarboxylate,as a common compound, the synthetic route is as follows.

To a de-gassed solution of 78 THF (325 ml) and 56 DIPEA (12.74 ml, 73.14 mmol) under a nitrogen atmosphere was added 113 7-bromo-4,6-dichloro-8-fluoro-3-nitroquinoline (26.59 g, 66.49 mmol) and 272 1-(tert-butyl) 3-methyl (R)-piperazine-1,3-dicarboxylate (17.05 g, 69.81 mmol). The resultant brown solution was heated at 61 C. (internal temperature) under a nitrogen atmosphere for 18 hours. Additional DIPEA (5.8 ml, 33.24 mmol) and 1-(tert-butyl) 3-methyl (R)-piperazine-1,3-dicarboxylate (8.12 g, 33.24 mmol) was then added and the resultant reaction mixture was heated at 61 C. (internal) for 4 hours. The reaction mixture was concentrated in vacuo, and the crude product was purified by flash silica chromatography, elution gradient 0 to 50% 57 ethyl acetate in 58 heptane. Pure fractions were evaporated to dryness to afford 273 1-tert-butyl 3-methyl (3R)-4-(7-bromo-6-chloro-8-fluoro-3-nitroquinolin-4-yl)piperazine-1,3-dicarboxylate (32.1 g, 88%) as an orange solid. 1H NMR (400 MHz, DMSO, 30 C.) 1.45 (9H, s), 2.52-2.53 (1H, m), 3.29-3.34 (1H, m), 3.56 (3H, s), 3.61-3.77 (2H, m), 3.78-3.93 (1H, m), 4.04-4.21 (1H, m), 4.33-4.4 (1H, m), 8.36 (1H, d), 9.16 (1H, s). m/z: ES+ [M+H]+ 547. 97% ee.

As the paragraph descriping shows that 438631-77-7 is playing an increasingly important role.

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.438631-77-7,(R)-1-tert-Butyl 3-methyl piperazine-1,3-dicarboxylate,as a common compound, the synthetic route is as follows.

To degassed mixture of 68 1,4-dioxane (74.3 ml) and 56 DIPEA (5.86 ml, 33.66 mmol) at rt was added 528 7-bromo-4-chloro-6,8-dimethyl-3-nitroquinoline (3.54 g, 11.22 mmol) followed by 272 1-tert-butyl 3-methyl (3R)-piperazine-1,3-dicarboxylate (4.11 g, 16.83 mmol). The reaction was heated at 100 C. for 48 h. The reaction was then cooled to rt and the solvent was removed in vacuo. The residue was diluted with EtOAc (300 ml) and washed with water (2×250 ml) and brine (100 ml). The organic layer was dried (phase separator) and concentrated in vacuo. The crude product was purified by flash silica chromatography (0 to 50% 57 EtOAc in 58 heptane) to give 530 1-tert-butyl 3-methyl (3R)-4-(7-bromo-6,8-dimethyl-3-nitroquinolin-4-yl)piperazine-1,3-dicarboxylate (4.79 g, 82%) as an orange oil; 1H NMR (400 MHz, DMSO, 30 C.) 1.45 (9H, s), 2.64 (3H, s), 2.88 (3H, s), 3.13-3.21 (1H, m), 3.51 (3H, s), 3.51-3.62 (2H, m), 3.8-3.89 (2H, m), 4.03 (1H, s), 4.31 (1H, s), 8.13 (1H, s), 9.06 (1H, s); m/z: ES+ [M+H]+ 524.9.

438631-77-7, As the paragraph descriping shows that 438631-77-7 is playing an increasingly important role.

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.438631-77-7,(R)-1-tert-Butyl 3-methyl piperazine-1,3-dicarboxylate,as a common compound, the synthetic route is as follows.

To degassed mixture of 68 1,4-dioxane (74.3 ml) and 56 DIPEA (5.86 ml, 33.66 mmol) at rt was added 528 7-bromo-4-chloro-6,8-dimethyl-3-nitroquinoline (3.54 g, 11.22 mmol) followed by 272 1-tert-butyl 3-methyl (3R)-piperazine-1,3-dicarboxylate (4.11 g, 16.83 mmol). The reaction was heated at 100 C. for 48 h. The reaction was then cooled to rt and the solvent was removed in vacuo. The residue was diluted with EtOAc (300 ml) and washed with water (2×250 ml) and brine (100 ml). The organic layer was dried (phase separator) and concentrated in vacuo. The crude product was purified by flash silica chromatography (0 to 50% 57 EtOAc in 58 heptane) to give 530 1-tert-butyl 3-methyl (3R)-4-(7-bromo-6,8-dimethyl-3-nitroquinolin-4-yl)piperazine-1,3-dicarboxylate (4.79 g, 82%) as an orange oil; 1H NMR (400 MHz, DMSO, 30 C.) 1.45 (9H, s), 2.64 (3H, s), 2.88 (3H, s), 3.13-3.21 (1H, m), 3.51 (3H, s), 3.51-3.62 (2H, m), 3.8-3.89 (2H, m), 4.03 (1H, s), 4.31 (1H, s), 8.13 (1H, s), 9.06 (1H, s); m/z: ES+ [M+H]+ 524.9.

438631-77-7, As the paragraph descriping shows that 438631-77-7 is playing an increasingly important role.

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

438631-77-7, (R)-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

To a solution of 7-bromo-4,6-dichloro-3-nitroquinoline (4.97 g, 15.44 mmol) in THF (100 mL) was added 1-tert-butyl 3-methyl (3R)-piperazine-1,3-dicarboxylate (4.9 g, 20.07 mmol) followed by DIPEA (8.07 mL, 46.31 mmol) and reaction mixture heated at reflux overnight. Further 1-tert-butyl 3-methyl (3R)-piperazine-1,3-dicarboxylate (0.943 g, 0.25 eq) was added, along with further DIPEA (1.35 mL, 0.5 eq) and the reaction mixture heated at reflux for a further 24 h. The reaction mixture was partially concentrated and partitioned between water and EtOAc. Layers were separated, the organic layer washed with water and the combined aqueous layers were back extracted with EtOAc. The combined organic layers were dried (phase separator) and concentrated in vacuo to afford crude material as a dark brown oil. This was purified by flash silica chromatography (0 to 18% EtOAc in heptane) to afford 1-tert-butyl 3-methyl (3R)-4-(7-bromo-6-chloro-3-nitroquinolin-4-yl)piperazine-1,3-dicarboxylate (5.2 g, 64%) as an orange foam; 1H NMR (400 MHz, DMSO, 30 C.) 1.44 (9H, s), 3.29 (2H, s), 3.5-3.58 (3H, m), 3.6-3.69 (1H, m), 3.73 (1H, dd), 3.78-3.9 (1H, m), 4.02-4.2 (1H, m), 4.3-4.38 (1H, m), 8.49 (1H, s), 8.52 (1H, s), 9.11 (1H, s); m/z: ES+ [M+H]+ 529, 531.

438631-77-7, The synthetic route of 438631-77-7 has been constantly updated, and we look forward to future research findings.

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.438631-77-7,(R)-1-tert-Butyl 3-methyl piperazine-1,3-dicarboxylate,as a common compound, the synthetic route is as follows.,438631-77-7

To (R)-1-tert-butyl 3-methylpiperazine-1,3-dicarboxylate (1.2 g, 4.9 mmol, ASW Med Chem Inc) in MeCN and MeOH (1:1, 100 mL) was added formaldehyde (37% aqueous, 13.2 mL, 177 mmol), followed by the addition of sodium triacetoxyborohydride (5.20 g, 24.5 mmol). The mixture was stirred for about 15 min at ambient temperature. AcOH (5.6 mL, 98 mmol) was added drop-wise and the mixture was stirred for about 1 h. The solvent was removed under reduced pressure and the residue was dissolved in DCM (100 mL) and neutralized using aqueous 2 N NaOH. Saturated aqueous NaHCO3 (50 mL) was added and the layers were separated. The organic layer was washed with brine (50 mL), dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The crude material was purified by silica gel chromatography eluting with a gradient of 20-80% EtOAc/heptane to afford (R)-1-tert-butyl 3-methyl 4-methylpiperazine-1,3-dicarboxylate (1.1 g, 85%): LC/MS (Table 2, Method a) Rt=1.91 min; MS m/z: 259 (M+H)+.

438631-77-7 (R)-1-tert-Butyl 3-methyl piperazine-1,3-dicarboxylate 6558432, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; ABBOTT LABORATORIES; US2009/312338; (2009); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

438631-77-7, (R)-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

Representative Synthesis I; (R)-l-(4-Chloro-benzyl)-piperazine-2-carboxylic acid methyl ester; R-4N-Boc-piperazine 2-carboxylic acid methyl ester (679.4mg, 2.78mmol) and 4- chlorobenzaldehyde (390.94mg, 2.78mmol) are mixed in dichloromethane(lthetaml) for 30 minutes. Sodium triacetoxyborohydride (800mg, 3.77mmol) is added. The mixture is stirred at room temperature for 16 hf . Water is added. The aqueous layer is extracted with dichloromethane twice (3OmL x2). The dichloromethane solution is treated with trifluoracetic acid (30ml). After 4 hrs the solvent is evaporated and re-disolved in water. The water solution is basified by adding K2CO3 (solid). The water solution is extracted with EtOAc three times. The organic layer is dried over NaSO4. The product is colorless oil (748mg, 100% ) after removing solvent to dryness. Found reta/z ES+=269 . ‘ . .

438631-77-7, 438631-77-7 (R)-1-tert-Butyl 3-methyl piperazine-1,3-dicarboxylate 6558432, apiperazines compound, is more and more widely used in various fields.

Reference£º
Patent; NOVARTIS AG; NOVARTIS PHARMA GmbH; WO2007/120595; (2007); A2;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

438631-77-7, (R)-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

Method 4:Synthesis of methyl (2R)-l-r5-(3-{l-r6-(2-aminopyrimidin-5-yl)pyridin-3- yl1cvclobutyl}-l,2,4-oxadiazol-5-yl)pyridin-2-yl1piperazine-2-carboxylate (Example 38, Table 1)Ex. 99 R30Example 99 (120 mg, 0.296 mmol) is treated with R30 (361 mg, 1.48 mmol) and NMP (0.150 mL) and heated at 80 C for 48 hours. The resulting mixture is cooled to room temperature and treated with 4N HC1 in 1,4-dioxane (1.50 mL) and stirred for 1.5 hours The resulting mixture is purified by reverse-phase preparative HPLC (C-18 silica, 10- 30% acetonitrile/water/0.1% trifluoroacetic acid over 20 minutes) to afford the title compound as a trifluoroacetic acid salt (110 mg), m/z 514.8 [M+H].

438631-77-7, As the paragraph descriping shows that 438631-77-7 is playing an increasingly important role.

Reference£º
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; BARTOLOZZI, Alessandra; BOSANAC, Todd; CHEN, Zhidong; DE LOMBAERT, Stephane; DINES, Jonathon, Alan; HUBER, John, D.; LIU, Weimin; LOKE, Pui Leng; MORWICK, Tina, Marie; OLAGUE, Alan; RIETHER, Doris; TYE, Heather; WU, Lifen; ZINDELL, Renee, M.; WO2012/40139; (2012); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

438631-77-7,With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.438631-77-7,(R)-1-tert-Butyl 3-methyl piperazine-1,3-dicarboxylate,as a common compound, the synthetic route is as follows.

To a de-gassed solution of 78 THF (325 ml) and 56 DIPEA (12.74 ml, 73.14 mmol) under a nitrogen atmosphere was added 113 7-bromo-4,6-dichloro-8-fluoro-3-nitroquinoline (26.59 g, 66.49 mmol) and 272 1-(tert-butyl) 3-methyl (R)-piperazine-1,3-dicarboxylate (17.05 g, 69.81 mmol). The resultant brown solution was heated at 61 C. (internal temperature) under a nitrogen atmosphere for 18 hours. Additional DIPEA (5.8 ml, 33.24 mmol) and 1-(tert-butyl) 3-methyl (R)-piperazine-1,3-dicarboxylate (8.12 g, 33.24 mmol) was then added and the resultant reaction mixture was heated at 61 C. (internal) for 4 hours. The reaction mixture was concentrated in vacuo, and the crude product was purified by flash silica chromatography, elution gradient 0 to 50% 57 ethyl acetate in 58 heptane. Pure fractions were evaporated to dryness to afford 273 1-tert-butyl 3-methyl (3R)-4-(7-bromo-6-chloro-8-fluoro-3-nitroquinolin-4-yl)piperazine-1,3-dicarboxylate (32.1 g, 88%) as an orange solid. 1H NMR (400 MHz, DMSO, 30 C.) 1.45 (9H, s), 2.52-2.53 (1H, m), 3.29-3.34 (1H, m), 3.56 (3H, s), 3.61-3.77 (2H, m), 3.78-3.93 (1H, m), 4.04-4.21 (1H, m), 4.33-4.4 (1H, m), 8.36 (1H, d), 9.16 (1H, s). m/z: ES+ [M+H]+ 547. 97% ee.

As the paragraph descriping shows that 438631-77-7 is playing an increasingly important role.

Reference£º
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

438631-77-7,With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.438631-77-7,(R)-1-tert-Butyl 3-methyl piperazine-1,3-dicarboxylate,as a common compound, the synthetic route is as follows.

(R)-l-(4-Chlorophenyl)-piperazine-2-carboxylic acid methyl esterR-4N-Boc-piperazine 2-carboxylic acid methyl ester (4.0gms, 16.4mmol) and 4- chlorophenylboronic acid (5.0gms, 32.8mmol) are mixed in dichloromethane (5OmI) . followed by addition of cupric acetate (3.0gms, 16.4mmol), 4 A molecular sieves (1 gm) and pyridine (3.28ml, 32.8mmol). The mixture is stirred at room temperature for 50 hr. The reaction mixture is concentrated directly in vacuo, diluted with ethyl acetate, and filtered through Celite. The organic filtrate is concentrated and the remaining residue is purified over silica gel column chromatography eluting with hexane and ethyl acetate to give 860 mg as a white solid.

As the paragraph descriping shows that 438631-77-7 is playing an increasingly important role.

Reference£º
Patent; NOVARTIS AG; NOVARTIS PHARMA GmbH; WO2007/120595; (2007); A2;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics