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Chemical Structure| 1270982-05-2 Chemical Structure| 1270982-05-2

Structure of 1270982-05-2

Chemical Structure| 1270982-05-2

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Product Details of [ 1270982-05-2 ]

CAS No. :1270982-05-2
Formula : C11H22N2O3
M.W : 230.30
SMILES Code : O=C(N1CC(COC)NCC1)OC(C)(C)C
English Name :tert-Butyl 3-(methoxymethyl)piperazine-1-carboxylate
MDL No. :MFCD19688481

Safety of [ 1270982-05-2 ]

Application In Synthesis of [ 1270982-05-2 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 1270982-05-2 ]

[ 1270982-05-2 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 301673-16-5 ]
  • [ 74-88-4 ]
  • [ 1270982-05-2 ]
YieldReaction ConditionsOperation in experiment
10% Stage #1: tert-butyl 3-(hydroxymethyl)piperazine-1-carboxylate With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.25h; Stage #2: methyl iodide In tetrahydrofuran; mineral oil at 0 - 20℃; 157.1 A suspension of sodium hydride (0.10 g, 2.6 mmol, 60% in mineral oil) in THF (6.0 mL) at 0 °C, was treated with a solution of tert-butyl 3-(hydroxymethyl)piperazine-l- carboxylate (0.56 g, 2.6 mmol, racemic, AstaTech) in THF (6.0 mL). After 15 min, methyl iodide (0.16 mL, 2.6 mmol) was added. The mixture was allowed to warm to RT and stir for 1.5 h. The reaction was then quenched with water, and extracted with four portions of DCM. The combined extracts were dried over sodium sulfate, decanted and concentrated. Flash chromatography using a 40 g silica gel cartridge, eluting with a gradient from 0-15% MeOH in DCM afforded the purified desired product, as the second product to elute (60 mg, 10%). ¾ NMR (500 MHz, CDC13): δ 3.90 (br s, 2H), 3.37 (dd, 1H), 3.34 (s, 3H), 3.25 (dd, 1H), 2.99-2.92 (m, 1H), 2.90-2.79 (m, 2H), 2.72 (td, 1H), 2.57 (br s, 1H), 2.15 (br s, 1H), 1.45 (s, 9H); LCMS (M+H)+: 231.2.
  • 2
  • [ 1270982-05-2 ]
  • [ 1270982-08-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium hydrogencarbonate / acetonitrile / 96 h 2: potassium carbonate / N,N-dimethyl-formamide / 5 h
  • 3
  • [ 1270982-05-2 ]
  • [ 42879-03-8 ]
  • [ 1270982-06-3 ]
YieldReaction ConditionsOperation in experiment
78% With sodium hydrogencarbonate In acetonitrile for 96h; 157.2 Racemic tert-butyl 3 -(methoxymethyl)piperazine- 1 -carboxylate (54 mg, 0.23 mmol; from Step 1) was dissolved in acetonitrile (0.31 mL), and into the mixture was added 4- bromobut-2-enenitrile (51 mg, 0.35 mmol, as a mixture of E- and Z-isomers prepared as described in J. Am. Chem. Soc. (1940), 62; 974-7) followed by sodium bicarbonate (39 mg, 0.47 mmol). After 4 days, the mixture was filtered and solvent removed in vacuo. The residue was treated with IN HCl to pH 1, the aqueous solution was extracted with EtOAc, the extract was then discarded. The aqueous phase was then made basic by the addition of solid sodium bicarbonate, and the product was extracted with two portions of EtOAc. The extracts were washed with brine, dried over sodium sulfate, decanted and concentrated to afford product as a mixture of E- and Z- olefin isomers, which was used without further purification (54 mg, 78%). 'H NMR (400 MHz, CDC13): δ 6.74 (dt, 1H, trans), 6.63 (ddd, 1H, cis), 5.63 (dt, 1H, trans), 5.47 (dt, 1H, cis), 3.82-2.93 (m, 16H), 3.34 (s, 3H), 3.32 (s, 3H), 2.74 (dt, 1H), 2.68 (ddd, 1H), 2.57-2.48 (m, 2H), 2.40-2.21 (m, 2H), 1.45 (s, 18H); LCMS (M-tBu+2H)+: 240.1.
  • 4
  • [ 13036-50-5 ]
  • [ 1270982-05-2 ]
  • [ 1580440-77-2 ]
YieldReaction ConditionsOperation in experiment
60% With N-ethyl-N,N-diisopropylamine In acetonitrile at 140℃; for 36h; Microwave irradiation; Sealed tube; 144 2-Chloro-4-phenylpyrimidine (prepared as described in Example 137; 0.332 g, 1.74 mmol), tert-butyl 3-(methoxymethyl)piperazine-l-carboxylate (0.400 g, 1.74 mmol), N,N-diisopropylethylamine (0.61 mL, 3.49 mmol) and acetonitrile (8 mL) were loaded into a sealed microwave reaction vial. The mixture was heated with stirring in a microwave reactor for 36 hours at 140 °C. The reaction was then concentrated and the residue was partitioned between water and ethyl acetate. The organic layer was combined with a second ethyl acetate extract, dried (Na2S04) and concentrated. The crude product was purified by flash chromatography over silica using a dichloromethane/methanol eluant to afford tert-butyl 3-(methoxymethyl)-4-(4-phenylpyrimidin-2-yl)piperazine-l- carboxylate as a glassy, faint amber solid (0.397 g, 60%>). The t-butoxycarbonyl protecting group was removed from this compound using General Procedure G to afford 2-(2-(methoxymethyl)piperazin-l-yl)-4-phenylpyrimidine. The intermediate was, in turn, reacted with Intermediate 5 using General Procedure A to generate the title compound. 1H NMR (400 MHz, DMSO-d6) δ 8.47 (d, J = 5.1 Hz, 1H), 8.18-8.09 (m, 2H), 7.57-7.47 (m, 3H), 7.24 (d, J= 5.1 Hz, 1H), 5.65 (s, 0.5H), 5.61 (s, 0.5H), 4.99-4.84 (m, 1H), 4.58-4.42 (m, 1H), 4.13-3.93 (m, 2H), 3.56-3.35 (m, 2H), 3.29 (s, 1.5H), 3.28 (s, 1.5H), 3.25-3.03 (m, 2H), 3.01-2.65 (m, 7H), 2.37-2.28 (m, 1H), 1.86-1.61 (m, 4H), 1.55-1.21 (m, 5H) ppm. Purity: 99.4% (214 & 254 nm) UPLCMS; retention time: 0.83 min; (M+H+) 465.4.
  • 5
  • [ 1270982-05-2 ]
  • [ 1183945-90-5 ]
  • [ 3027194-30-2 ]
YieldReaction ConditionsOperation in experiment
78 mg Stage #1: tert-butyl 3-(methoxymethyl)piperazine-1-carboxylate; 3-bromo-4-methoxy-N-methyl-N-propylbenzenesulfonamide With palladium diacetate; caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In toluene Inert atmosphere; Reflux; Sealed tube; Stage #2: With hydrogenchloride In 1,4-dioxane; dichloromethane; ethyl acetate at 20℃; 4-methoxy-3-[2-(methoxymethyl)piperazin-1-yl]-N-methyl-N-propyl- benzenesulfonamide (I-017) A microwave reaction vial was charged with the aryl bromide I-009 (600mg, 1.86mmol, 1 equiv.), tert-butyl 3-(methoxymethyl) piperazine-1-carboxylate (429mg, 1.86mmol, 1 equiv.), Cs2CO3 (1.82g, 5.59mmol, 3 equiv.), Pd(OAc)2 (42mg, 0.19mmol, 0.1 equiv.) and rac-BINAP (174mg, 279µmol, 0.15 equiv.). The vial was flushed with argon and degassed toluene (9.5mL) was added. The vial was sealed and the reaction was stirred at reflux in a preheated heating-block for 3h. After cooling down to RT, EtOAc was added and the suspension was filtered over Celite (EtOAc rinses). The filtrate was concentrated under reduced pressure and purified by FC (DCM/EtOAc = 95/5 to 40/60). The residue was directly treated with HCl (4M solution in dioxane, 1.03mL, 4.14mmol, 10 equiv.). The mixture was stirred at RT for 16h. The reaction mixture was concentrated under reduced pressure and the residue was partitioned between water and DCM. K2CO3(s) was added portionwise until pH >11. The layers were separated and the aqueous phase was extracted with DCM (2*). The combined organic extracts were dried (Na2SO4), filtered and concentrated under Reduced pressure. residue was purified by FC (DCM/MeOH (7N NH3) = 99/1 to 90/10) to afford 78mg (8% over two steps) of I-017 as an orange oil.1H NMR (400 MHz, Chloroform-d) δ 7.46 (dd, J = 8.6, 2.0 Hz, 1H), 7.36 (d, J = 2.1 Hz, 1H), 6.94 (dd, J = 8.5, 1.6 Hz, 1H), 3.93 (d, J = 1.7 Hz, 3H), 3.80 (dt, J = 7.6, 3.7 Hz, 1H), 3.65-3.58 (m, 1H), 3.40-3.26 (m, 2H), 3.22 (d, J = 1.7 Hz, 3H), 3.19- 2.99 (m, 4H), 2.99-2.87 (m, 3H), 2.72 (d, J = 1.6 Hz, 3H), 1.56 (q, J = 7.4 Hz, 2H), 0.94 (td, J = 7.4, 1.6 Hz, 3H). MS (ESI+): [M+H]+ 372.2.
78 mg Stage #1: tert-butyl 3-(methoxymethyl)piperazine-1-carboxylate; 3-bromo-4-methoxy-N-methyl-N-propylbenzenesulfonamide With palladium diacetate; caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In toluene Inert atmosphere; Reflux; Sealed tube; Stage #2: With hydrogenchloride In 1,4-dioxane; dichloromethane; ethyl acetate at 20℃; 4-methoxy-3-[2-(methoxymethyl)piperazin-1-yl]-N-methyl-N-propyl- benzenesulfonamide (I-017) A microwave reaction vial was charged with the aryl bromide I-009 (600mg, 1.86mmol, 1 equiv.), tert-butyl 3-(methoxymethyl) piperazine-1-carboxylate (429mg, 1.86mmol, 1 equiv.), Cs2CO3 (1.82g, 5.59mmol, 3 equiv.), Pd(OAc)2 (42mg, 0.19mmol, 0.1 equiv.) and rac-BINAP (174mg, 279µmol, 0.15 equiv.). The vial was flushed with argon and degassed toluene (9.5mL) was added. The vial was sealed and the reaction was stirred at reflux in a preheated heating-block for 3h. After cooling down to RT, EtOAc was added and the suspension was filtered over Celite (EtOAc rinses). The filtrate was concentrated under reduced pressure and purified by FC (DCM/EtOAc = 95/5 to 40/60). The residue was directly treated with HCl (4M solution in dioxane, 1.03mL, 4.14mmol, 10 equiv.). The mixture was stirred at RT for 16h. The reaction mixture was concentrated under reduced pressure and the residue was partitioned between water and DCM. K2CO3(s) was added portionwise until pH >11. The layers were separated and the aqueous phase was extracted with DCM (2*). The combined organic extracts were dried (Na2SO4), filtered and concentrated under Reduced pressure. residue was purified by FC (DCM/MeOH (7N NH3) = 99/1 to 90/10) to afford 78mg (8% over two steps) of I-017 as an orange oil.1H NMR (400 MHz, Chloroform-d) δ 7.46 (dd, J = 8.6, 2.0 Hz, 1H), 7.36 (d, J = 2.1 Hz, 1H), 6.94 (dd, J = 8.5, 1.6 Hz, 1H), 3.93 (d, J = 1.7 Hz, 3H), 3.80 (dt, J = 7.6, 3.7 Hz, 1H), 3.65-3.58 (m, 1H), 3.40-3.26 (m, 2H), 3.22 (d, J = 1.7 Hz, 3H), 3.19- 2.99 (m, 4H), 2.99-2.87 (m, 3H), 2.72 (d, J = 1.6 Hz, 3H), 1.56 (q, J = 7.4 Hz, 2H), 0.94 (td, J = 7.4, 1.6 Hz, 3H). MS (ESI+): [M+H]+ 372.2.
 

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