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Simple exploration of 1403898-64-5

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.

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 5: (2R,5R)-4-Benzyl-5-hydroxymethyl-2-methyl-pi perazi ne-I -carboxyl icacid tert-butyl esterA mixture of (2 R,5R)-5-hydroxymethyl-2-methyl-piperazine- 1 -carboxylic acid tert-butyl ester (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 partitionedbetween saturated aqueous NaHCO3 (150 mL) and DCM (3 x 50 mL). Combined organic extracts were dried (Na2SO4) then evaporated 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, 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; WO2014/60770; (2014); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

Some tips on 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.

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.

DIPEA (7.7 ml, 44.2 mmol) was added slowly to a stirred solution of 472 7-bromo-4,6-dichloro-8-methyl-3-nitroquinoline (9.9 g, 29.47 mmol) and 180 tert-butyl (2R,5R)-5-(hydroxymethyl)-2-methylpiperazine-1-carboxylate (8.82 g, 38.31 mmol) in 63 DCM (100 ml) at rt. The resulting solution was stirred at rt for 64 h and then concentrated in vacuo to afford crude product, which was purified by flash silica chromatography (0 to 40% 57 EtOAc in 58 heptane) to give 487 tert-butyl (2R,5R)-4-(7-bromo-6-chloro-8-methyl-3-nitroquinolin-4-yl)-5-(hydroxymethyl)-2-methylpiperazine-1-carboxylate (8.9 g, 57%) as an orange solid; 1H NMR (400 MHz, DMSO, 30 C.) 1.22 (3H, d), 1.45 (9H, s), 2.91 (3H, s), 2.93-3.02 (1H, m), 3.46-3.68 (3H, m), 3.68-3.81 (2H, m), 4.02 (1H, d), 4.22-4.38 (1H, m), 4.62 (1H, t), 8.22 (1H, s), 9.05 (1H, s); m/z: ES+ [M+H]+ 529.2., 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£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

Analyzing the synthesis route of (2R,5R)-tert-Butyl 5-(hydroxymethyl)-2-methylpiperazine-1-carboxylate

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

Preparation 5: (2R,5R)-4-Benzyl-5-hydroxymethyl-2-methyl-pi perazi ne-I -carboxylic acidtert-butyl ester A mixture of (2 R,5R)-5-hydroxymethyl-2-methyl-piperazine- 1 -carboxylic acid tert-butyl ester(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 at2O c for 18 h, then partitionedbetween saturated aqueous NaHCO3 (150 mL) and DCM (3 x 50 mL). Combined organic extracts were dried (Na2SO4) then evaporated 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

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

Reference£º
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

Downstream synthetic route of (2R,5R)-tert-Butyl 5-(hydroxymethyl)-2-methylpiperazine-1-carboxylate

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

DIPEA (1.517 mL, 8.68 mmol) was added to 505 7-bromo-4-chloro-6,8-difluoro-3-nitroquinoline (702 mg, 2.17 mmol) and 180 tert-butyl (2R,5R)-5-(hydroxymethyl)-2-methylpiperazine-1-carboxylate (500 mg, 2.17 mmol) in 78 THF (8 mL) at 25 C. The resulting solution was stirred at 80 C. for 4 h. The solvent was removed in vacuo. The crude product was purified by flash silica chromatography (10 to 50% 57 EtOAc in 148 petroleum ether) to afford 732 tert-butyl (2R,5R)-4-(7-bromo-6,8-difluoro-3-nitroquinolin-4-yl)-5-(hydroxymethyl)-2-methylpiperazine-1-carboxylate (861 mg, 77%) as a yellow solid; 1H NMR (400 MHz, DMSO, 30 C.) 1.21 (3H, d), 1.44 (9H, s), 2.84-3.00 (1H, m), 3.27-3.34 (1H, m), 3.47-3.68 (2H, m), 3.70-3.84 (2H, m), 3.97-4.08 (1H, m), 4.21-4.33 (1H, m), 4.64 (1H, t), 7.92 (1H, dd), 9.02 (1H, s); m/z: ES+ [M+H]+=517., 1403898-64-5

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

Brief introduction of 1403898-64-5

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

A stirred solution of 113 7-bromo-4,6-dichloro-8-fluoro-3-nitroquinoline (2 g, 5.88 mmol) and 180 tert-butyl (2R,5R)-5-(hydroxymethyl)-2-methylpiperazine-1-carboxylate (1.355 g, 5.88 mmol) in 142 MeCN (30 mL) was treated with 56 DIPEA (1.025 mL, 5.88 mmol) and the reaction mixture stirred at 80 C. for 75 min. The reaction mixture was concentrated in vacuo and purified by flash silica chromatography (0 to 40% 57 EtOAc in 58 heptane) to give 444 tert-butyl (2R,5R)-4-(7-bromo-6-chloro-8-fluoro-3-nitroquinolin-4-yl)-5-(hydroxymethyl)-2-methylpiperazine-1-carboxylate (2.6 g, 83%) as a yellow solid; m/z: ES+ [M+H]+ 533/535.

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

Analyzing the synthesis route of 1403898-64-5

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

Preparation 46: (2R,5R) -4-(2,4-Di methoxy-benzyl)-5-hydroxymethyl-2-methyl-pi perazi ne1-carboxylic acid tert-butyl ester To an ice-cooled solution of (2R ,5R)-5-hydroxymethyl-2-methyl-piperazine- 1 -carboxylic acid tert-butyl ester (10.0 g, 43.5 mmol) in DOE (70 mL) were added 2,4-dimethoxy-benzaldehyde (11.1 g, 66.6 mmol) and sodium triacetoxyborohydride(11.1 g, 52.2 mmol) in small portions. Thereaction mixture was stirred at room temperature overnight. Saturated aqueous NaHCO3 was added and the product was extracted with DCM. The organic phase was dried and evaporated. Chromatography on silica gel, eluting with petrol – EtOAc 0-50% gave the title compound (16.3 g, 99%). 1297-012-1 MS: [M+H] = 381., 1403898-64-5

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

Brief introduction of 1403898-64-5

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

Preparation 10: (2R,5R)-2-Hydroxymethyl-5-methyl-piperazine-1 ,4-dicarboxylic acid 1 – benzyl ester 4-ferf-butyl esterTo (2R,5R)-5-hydroxymethyl-2-methyl-piperazine-1 -carboxylic acid ie f-butyl ester (21 g, 90 mmol) in THF (210 mL) at 3-4 C (ice bath) was added 1 M aqueous NaOH (99.5 mL) and benzyl chloroformate (12.9 mL, 90.43 mmol). After stirring for 1 h at the same temperature, the mixture was left to stir for another 1 h and then warmed to RT. The organic layer was separated and the aqueous phase extracted with EtOAc (2 x 50 mL). The combined organic extracts were washed with saturated brine solution (150 mL), then dried over sodium sulfate, filtered and concentrated. The crude oil was purified by column chromatography on silica gel (gradient elution, 0 – 100%, EtOAc/petrol), to give the title compound (26 g) as a pale yellow oil, used directly in Preparation 1 1 . 1H NMR (Me-d3-OD): 7.47-7.15 (5H, m), 5.26-5.07 (2H, m), 4.25 (2H, s), 4.04-3.88 (1 H, m), 3.83 (1 H, d), 3.61 (2H, bs), 3.31 -3.09 (2H, m), 1 .48 (9H, s), 1.14 (3H, t)., 1403898-64-5

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

Reference£º
Patent; ASTEX THERAPEUTICS LIMITED; WOOLFORD, Alison Jo-Anne; HOWARD, Steven; BUCK, Ildiko Maria; CHESSARI, Gianni; JOHNSON, Christopher Norbert; TAMANINI, Emiliano; DAY, James Edward Harvey; CHIARPARIN, Elisabetta; HEIGHTMAN, Thomas Daniel; FREDERICKSON, Martyn; GRIFFITHS-JONES, Charlotte Mary; WO2012/143726; (2012); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

New learning discoveries about 1403898-64-5

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

A solution of 180 tert-butyl (2R,5R)-5-(hydroxymethyl)-2-methylpiperazine-1-carboxylate (18.5 g, 80.33 mmol) in 78 THF (190 ml) was cooled in an ice-bath to 0 C. Aqueous 1M 38 sodium hydroxide solution (88 ml, 88.36 mmol) was added, followed by 317 benzyl chloroformate (11.99 ml, 84.34 mmol) (internal reaction temperature kept 57 ethyl acetate in 58 heptane. Pure fractions were evaporated to dryness to afford 318 1-benzyl 4-tert-butyl (2R,5R)-2-(hydroxymethyl)-5-methylpiperazine-1,4-dicarboxylate (25.4 g, 87%) as a colourless oil. 1H NMR (400 MHz, CD3OD, 30 C.): 1.12 (3H, dd), 1.46 (9H, s), 3.1-3.29 (2H, m), 3.53-3.66 (2H, m), 3.81 (1H, d), 3.88-4.02 (1H, m), 4.15-4.38 (2H, m), 5.06-5.26 (2H, m), 7.21-7.51 (5H, m). One exchangeable proton not seen. m/z: ES+ [M-Boc]=265.1., 1403898-64-5

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

New learning discoveries about 1403898-64-5

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

To a solution of l-(2-chloroacetyl)-6-(4-fluorobenzyl)-3,3-dimethyl-2,3-dihydro-lH-pyrrolo[3,2- b]pyridin-5(4H)-one (0.5 g, 1.44 mmol) and triethylamine (0.44g, 4.5 mmol) in THF (10 mL) was added (2R,5R)-tert-butyl 5-(hydroxymethyl)-2-methylpiperazine-l-carboxylate (0.3 g, 1.30 mmol) and the reaction was stirred at 80 C overnight. To the reaction mixture was added 20 ml of water and 20 ml of ethyl acetate, the organic layer was separated and evaporated to dryness. The residue was purified by flash chromatography on silica gel, eluting with methanol : dichloromethane = 1:20 to afford the title compound (450 mg, 0.83 mmol, 64 % yield). LCMS Method D RT= 1.35 min, ES+ve 543.

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

Reference£º
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

Downstream synthetic route of 1403898-64-5

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

A mixture of (2 R,5R)-5-hydroxymethyl-2-methyl-piperazine- 1 -carboxylic acid tert-butyl ester (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 partitionedbetween saturated aqueous NaHCO3 (150 mL) and DCM (3 x 50 mL). Combined organic extracts were dried (Na2SO4) then evaporated 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.

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

Reference£º
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