Category: 1403898-64-5

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.1403898-64-5,(2R,5R)-tert-Butyl 5-(hydroxymethyl)-2-methylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

To a solution of tert-butyl (2R,5R)-5-(hydroxymethyl)-2-methylpiperazine-1- carboxylate (100 mg, 0.43 mmol) in acetonitrile (5 mL) was added DIPEA (0.76 mL, 4.34 mmol) at room temperature. After 5 min, 4,4′-(bromomethylene) bis(fluorobenzene) (148 mg, 0.52 mmol) was added and the reaction mixture was heated at 80 C for 12 h. The reaction mixture was cooled to room temperature, the solvent was removed under reduced pressure and the crude product was purified by Combiflash using a 12 g silica gel column and eluted with 5-10% MeOH in DCM. The required fractions concentrated to obtain tert-butyl (2R,5R)-4-(bis(4-fluorophenyl)methyl)-5-(hydroxymethyl)-2- methylpiperazine-1-carboxylate (130 mg, 69.2 % yield) as an off-white solid; LCMS: m/z,433.4 (M+H); rt 2.15 min. LCMS Method Column Name: AQUITY UPLC BEH C18(3.0 x 50 mm) 1.7 ^m Buffer:10 mM ammonium acetate Mobile Phase A: Buffer: acetonitrile (95:5) Mobile phase B: Buffer: acetonitrile (5:95) Method: %B: 0 min- 20:2min -100: 2.2 min-100 Flow: 0.7 mL/min, 1403898-64-5

As the paragraph descriping shows that 1403898-64-5 is playing an increasingly important role.

Reference：
Patent; BRISTOL-MYERS SQUIBB COMPANY; VELAPARTHI, Upender; CHUPAK, Louis S.; DARNE, Chetan Padmakar; DING, Min; GENTLES, Robert G.; HUANG, Yazhong; KAMBLE, Manjunatha Narayana Rao; MARTIN, Scott W.; MANNOORI, Raju; MCDONALD, Ivar M.; OLSON, Richard E.; RAHAMAN, Hasibur; JALAGAM, Prasada Rao; ROY, Saumya; TONUKUNURU, Gopikishan; VELAIAH, Sivasudar; WARRIER, Jayakumar Sankara; ZHENG, Xiaofan; TOKARSKI, John S.; DASGUPTA, Bireshwar; REDDY, Kotha Rathnakar; RAJA, Thiruvenkadam; (0 pag.)WO2020/6018; (2020); 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.1403898-64-5,(2R,5R)-tert-Butyl 5-(hydroxymethyl)-2-methylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

To a solution of tert-butyl (2R,5R)-5-(hydroxymethyl)-2-methylpiperazine-1- carboxylate (100 mg, 0.43 mmol) in acetonitrile (5 mL) was added DIPEA (0.76 mL, 4.34 mmol) at room temperature. After 5 min, 4,4′-(bromomethylene) bis(fluorobenzene) (148 mg, 0.52 mmol) was added and the reaction mixture was heated at 80 C for 12 h. The reaction mixture was cooled to room temperature, the solvent was removed under reduced pressure and the crude product was purified by Combiflash using a 12 g silica gel column and eluted with 5-10% MeOH in DCM. The required fractions concentrated to obtain tert-butyl (2R,5R)-4-(bis(4-fluorophenyl)methyl)-5-(hydroxymethyl)-2- methylpiperazine-1-carboxylate (130 mg, 69.2 % yield) as an off-white solid; LCMS: m/z,433.4 (M+H); rt 2.15 min. LCMS Method Column Name: AQUITY UPLC BEH C18(3.0 x 50 mm) 1.7 ^m Buffer:10 mM ammonium acetate Mobile Phase A: Buffer: acetonitrile (95:5) Mobile phase B: Buffer: acetonitrile (5:95) Method: %B: 0 min- 20:2min -100: 2.2 min-100 Flow: 0.7 mL/min, 1403898-64-5

As the paragraph descriping shows that 1403898-64-5 is playing an increasingly important role.

Reference：
Patent; BRISTOL-MYERS SQUIBB COMPANY; VELAPARTHI, Upender; CHUPAK, Louis S.; DARNE, Chetan Padmakar; DING, Min; GENTLES, Robert G.; HUANG, Yazhong; KAMBLE, Manjunatha Narayana Rao; MARTIN, Scott W.; MANNOORI, Raju; MCDONALD, Ivar M.; OLSON, Richard E.; RAHAMAN, Hasibur; JALAGAM, Prasada Rao; ROY, Saumya; TONUKUNURU, Gopikishan; VELAIAH, Sivasudar; WARRIER, Jayakumar Sankara; ZHENG, Xiaofan; TOKARSKI, John S.; DASGUPTA, Bireshwar; REDDY, Kotha Rathnakar; RAJA, Thiruvenkadam; (0 pag.)WO2020/6018; (2020); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

1403898-64-5, (2R,5R)-tert-Butyl 5-(hydroxymethyl)-2-methylpiperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

To a solution of 6-(4-fluorobenzyl)-3,3,4-trimethyl-2,3-dihydro-lH-pyrrolo[3,2-b]pyridin-5(4H)-one (190 mg, 0.66 mmol) in DCM (3.00 mL) and was added triethylamine (0.277 mL, 1.99 mmol) and the reaction was stirred at room temperature under an atmosphere of nitrogen. Chloroacetyl chloride (0.058 mL, 0.730 mmol) was added and the reaction was stirred at room temperature for 30 minutes. The reaction was diluted in 25 mL DCM and washed with 10 mL saturated sodium bicarbonate solution, 10 mL water and 10 mL brine. The organic layer was passed through a biotage phase separator and concentrated under vacuum. The residue was dissolved in 3 mL THF and triethylamine (0.28 mL, 1.99 mmol) and (2R,5R)-tert-butyl 5-(hydroxymethyl)-2-methylpiperazine-l- carboxylate (199 mg, 0.86 mmol, obtained as described in WO 2012/143726) was added. The reaction was stirred at 60C for 18h, then was diluted in 25 mL EtOAc and washed with 2 x 10 mL water and 10 mL brine. The organic layer was passed a through biotage phase separator and concentrated under vacuum to afford the title compound (170 mg, 0.31 mmol, 46 % yield). LCMS Method A RT= 0.84 min, ES+ve 557.

1403898-64-5, 1403898-64-5 (2R,5R)-tert-Butyl 5-(hydroxymethyl)-2-methylpiperazine-1-carboxylate 71003242, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; CASILLAS, Linda N.; HARLING, John David; MIAH, Afjal Hussain; SMITH, Ian Edward David; RACKHAM, Mark David; (204 pag.)WO2017/182418; (2017); 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.1403898-64-5,(2R,5R)-tert-Butyl 5-(hydroxymethyl)-2-methylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

A mixture of (2R ,5R)-5-hydroxymethyl-2-methyl-piperazine- 1 -carboxylic acid tert-butyl ester(which may be prepared as described in Preparation 4) (3.48 g, 15.1 mmol), benzaldehyde(1.76 g, 16.6 mmol), sodium triacetoxyborohydride (3.84 g, 18.1 mmol) and 1,2-dichloroethane(30 mL) was stirred at 20 C for 18 h, then partitioned between saturated aqueous NaHCO3(150 mL) and DCM (3 x 50 mL). Combined organic extracts were dried (Na2SO4) thenevaporated in vacuo to give an oil. Chromatography (Si02, 0 – 30% EtOAc in petrol) gave the title compound (4.588 g, 74%) as a colourless solid. MS: [M+H] = 321., 1403898-64-5

As the paragraph descriping shows that 1403898-64-5 is playing an increasingly important role.

Reference：
Patent; ASTEX THERAPEUTICS LIMITED; CHESSARI, Gianni; JOHNSON, Christopher Norbert; HOWARD, Steven; DAY, James Edward Harvey; BUCK, Ildiko Maria; GRIFFITHS-JONES, Charlotte Mary; SAXTY, Gordon; TAMANINI, Emiliano; WILSHER, Nicola Elisabeth; WO2015/92420; (2015); 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.1403898-64-5,(2R,5R)-tert-Butyl 5-(hydroxymethyl)-2-methylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

A mixture of (2R ,5R)-5-hydroxymethyl-2-methyl-piperazine- 1 -carboxylic acid tert-butyl ester(which may be prepared as described in Preparation 4) (3.48 g, 15.1 mmol), benzaldehyde(1.76 g, 16.6 mmol), sodium triacetoxyborohydride (3.84 g, 18.1 mmol) and 1,2-dichloroethane(30 mL) was stirred at 20 C for 18 h, then partitioned between saturated aqueous NaHCO3(150 mL) and DCM (3 x 50 mL). Combined organic extracts were dried (Na2SO4) thenevaporated in vacuo to give an oil. Chromatography (Si02, 0 – 30% EtOAc in petrol) gave the title compound (4.588 g, 74%) as a colourless solid. MS: [M+H] = 321., 1403898-64-5

As the paragraph descriping shows that 1403898-64-5 is playing an increasingly important role.

Reference：
Patent; ASTEX THERAPEUTICS LIMITED; CHESSARI, Gianni; JOHNSON, Christopher Norbert; HOWARD, Steven; DAY, James Edward Harvey; BUCK, Ildiko Maria; GRIFFITHS-JONES, Charlotte Mary; SAXTY, Gordon; TAMANINI, Emiliano; WILSHER, Nicola Elisabeth; WO2015/92420; (2015); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

1403898-64-5, (2R,5R)-tert-Butyl 5-(hydroxymethyl)-2-methylpiperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Preparation 18: (2R,5R)-4-{2-[6-(4-FI uoro-benzyl)-3,3-di methyl-2,3-di hydro-pyrrolo[3,2- b]pyridi n-I -yI]-2-oxo-ethyl}-5-hydroxymethyl-2-methyl-pi perazi ne-I -carboxylic acid tert-butyl esterFinely ground potassium iodide (7.5 g, 45.26 mmol) was added to a mixture of (2R,5R)-5-hydroxymethyl-2-methyl-piperazine-1-carboxylic acid teit-butyl ester (5.7 g, 24.89 mmol), 2-chloro- 1 -[6-(4-fluorobenzyl)-3, 3-dimethyl-2, 3-dihydro-pyrrolo[3,2-b]pyridin- 1 -yl]-ethanone hydrochloride (8.35 g, 22.63 mmol) potassium carbonate (12.5 g, 90.51 mmol) and acetonitrile (100 mL) under nitrogen. The mixture was stirred at 20 00 overnight. The mixture was partitioned between water (300 mL) and EtOAc (300 mL) and the organic phasewas dried and evaporated in vacuo to give the title compound (12.14 g). MS: [M+H] = 527.

1403898-64-5, As the paragraph descriping shows that 1403898-64-5 is playing an increasingly important role.

Reference：
Patent; ASTEX THERAPEUTICS LIMITED; CHESSARI, Gianni; JOHNSON, Christopher Norbert; PAGE, Lee William; BUCK, Ildiko Maria; DAY, James Edward Harvey; HOWARD, Steven; SAXTY, Gordon; MURRAY, Christopher William; WO2014/60770; (2014); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

1403898-64-5, (2R,5R)-tert-Butyl 5-(hydroxymethyl)-2-methylpiperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Finely ground potassium iodide (7.5 g, 45.26 mmol) was added to a mixture of (2R,5R)-5- hydroxymethyl-2-methyl-piperazine- 1 -carboxylic acid teit-butyl ester (5.7 g, 24.89 mmol), 2- chloro- 1 -[6-(4-fluorobenzyl)-3, 3-dimethyl-2, 3-dihydro-pyrrolo[3,2-b]pyridin- 1 -yl]-ethanone hydrochloride (8.35 g, 22.63 mmol) potassium carbonate (12.5 g, 90.51 mmol) andacetonitrile (100 mL) under nitrogen. The mixture was stirred at 20 C overnight. The mixture was partitioned between water (300 mL) and EtOAc (300 mL) and the organic phase was dried and evaporated in vacuo to give the title compound (12.14 g). MS: [M+H] = 527., 1403898-64-5

The synthetic route of 1403898-64-5 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; ASTEX THERAPEUTICS LIMITED; CHESSARI, Gianni; JOHNSON, Christopher Norbert; PAGE, Lee William; MILLEMAGGI, Alessia; HOWARD, Steven; SAXTY, Gordon; HEIGHTMAN, Thomas Daniel; WO2014/60768; (2014); 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.1403898-64-5,(2R,5R)-tert-Butyl 5-(hydroxymethyl)-2-methylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

Tert-butyl (2R,5R)-5-(hydroxymethyl)-2-methylpiperazine-1-carboxylate (770 mg, 3.34 mmol), 181 tert-butylchlorodimethylsilane (756 mg, 5.02 mmol), 132 triethylamine (677 mg, 6.69 mmol) and 182 N,N-dimethylpyridin-4-amine (41 mg, 0.33 mmol) were dissolved in 63 DCM (6 ml) and the mixture was stirred at room temperature for 2 hours. The reaction was quenched with saturated 152 aqueous NH4Cl and extracted with DCM (3×30 ml). The organic phase was washed with brine and dried. The solvent was removed under reduced pressure and the crude product was purified by flash chromatography on a silica gel, eluting from 0-30% (57 EtOAc in 148 petroleum ether). The fractions containing the desired product were evaporated to dryness to afford 183 tert-butyl (2R,5R)-5-(((tert-butyldimethylsilyl)oxy)methyl)-2-methylpiperazine-1-carboxylate (1.04 g, 90%) as a colourless oil. 1H NMR (Chloroform-d, 400 MHz) 0.08 (6H, d), 0.91 (9H, s), 1.30 (3H, d), 1.47 (9H, s), 2.56 (1H, dd), 2.96-3.05 (1H, m), 3.10 (1H, dd), 3.30 (1H, dd), 3.55 (1H, dd), 3.68-3.82 (2H, m), 4.15-4.25 (1H, m), (1 exchangeable proton not seen). m/z (ES+), [M+H]+=345., 1403898-64-5

The synthetic route of 1403898-64-5 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.1403898-64-5,(2R,5R)-tert-Butyl 5-(hydroxymethyl)-2-methylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

Preparation 22: (2R,5R)-4-{2-[6-(4-FI uoro-benzyl)-3,3-di methyl-2,3-di hydro-pyrrolo[3,2- b]pyridi n-I -yI]-2-oxo-ethyl}-5-hydroxymethyl-2-methyl-pi perazi ne-I -carboxylic acid tertbutyl esterFinely ground potassium iodide (7.5 g, 45.26 mmol) was added to a mixture of (2R,5R)-5- hydroxymethyl-2-methyl-piperazine- 1 -carboxylic acid teit-butyl ester (5.7 g, 24.89 mmol), 2- chloro- 1 -[6-(4-fluorobenzyl)-3, 3-dimethyl-2, 3-dihydro-pyrrolo[3,2-b]pyridin- 1 -yl]-ethanone hydrochloride (8.35 g, 22.63 mmol) potassium carbonate (12.5 g, 90.51 mmol) and acetonitrile (100 mL) under nitrogen. The mixture was stirred at 20 C overnight. The mixture waspartitioned between water (300 mL) and EtOAc (300 mL) and the organic phase was dried and evaporated in vacuo to give the title compound (12.14 g). MS: [M+H] = 527.

1403898-64-5, 1403898-64-5 (2R,5R)-tert-Butyl 5-(hydroxymethyl)-2-methylpiperazine-1-carboxylate 71003242, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; ASTEX THERAPEUTICS LIMITED; CHESSARI, Gianni; JOHNSON, Christopher Norbert; PAGE, Lee William; BUCK, Ildiko Maria; DAY, James Edward Harvey; HOWARD, Steven; SAXTY, Gordon; MURRAY, Christopher William; HOPKINS, Anna; WO2014/60767; (2014); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

1403898-64-5, (2R,5R)-tert-Butyl 5-(hydroxymethyl)-2-methylpiperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

To a solution of 6-(4-fluorobenzyl)-3,3,4-trimethyl-2,3-dihydro-lH-pyrrolo[3,2-b]pyridin-5(4H)-one (190 mg, 0.66 mmol) in DCM (3.00 mL) and was added triethylamine (0.277 mL, 1.99 mmol) and the reaction was stirred at room temperature under an atmosphere of nitrogen. Chloroacetyl chloride (0.058 mL, 0.730 mmol) was added and the reaction was stirred at room temperature for 30 minutes. The reaction was diluted in 25 mL DCM and washed with 10 mL saturated sodium bicarbonate solution, 10 mL water and 10 mL brine. The organic layer was passed through a biotage phase separator and concentrated under vacuum. The residue was dissolved in 3 mL THF and triethylamine (0.28 mL, 1.99 mmol) and (2R,5R)-tert-butyl 5-(hydroxymethyl)-2-methylpiperazine-l- carboxylate (199 mg, 0.86 mmol, obtained as described in WO 2012/143726) was added. The reaction was stirred at 60C for 18h, then was diluted in 25 mL EtOAc and washed with 2 x 10 mL water and 10 mL brine. The organic layer was passed a through biotage phase separator and concentrated under vacuum to afford the title compound (170 mg, 0.31 mmol, 46 % yield). LCMS Method A RT= 0.84 min, ES+ve 557.

1403898-64-5, 1403898-64-5 (2R,5R)-tert-Butyl 5-(hydroxymethyl)-2-methylpiperazine-1-carboxylate 71003242, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; CASILLAS, Linda N.; HARLING, John David; MIAH, Afjal Hussain; SMITH, Ian Edward David; RACKHAM, Mark David; (204 pag.)WO2017/182418; (2017); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics