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CAS No. : | 31166-44-6 | MDL No. : | MFCD00274317 |
Formula : | C12H16N2O2 | Boiling Point : | - |
Linear Structure Formula : | C6H5CH2OCOC4N2H9 | InChI Key : | CTOUWUYDDUSBQE-UHFFFAOYSA-N |
M.W : | 220.27 | Pubchem ID : | 643495 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47% | With potassium phosphate;bis(tri-tert-butylphosphine)palladium(0); In ISOPROPYLAMIDE; at 100℃; | A mixture of methyl -bromo-l-benzothiophene-^-carboxylate (60 mg, 0.21 mmol), Cbz- piperazine (0.100 mL, 0.52 mmol) and K3PO4 (220 mg) in DMAc (1 mL) was degassed by the freeze- pump-thaw method. Next, Pd[P(tert-butyl)3]2 (20 mg) was added and the mixture stirred at 100C overnight. The crude mixture was partitioned between EtOAc and sat'd NaCl, the organic layer dried (Na2SO4) and concentrated. Chromatography on SiO2 (EtOAc/CH2Cl2, 0:100 to 10:90) gave 42 mg (47%) of the ethyl ester coupled product. A mixture of this ester in 2: 1: 1 THF/MeOH/water (2 mL) was treated with LiOH (10 mg, 0.24 mmol) and stirred overnight, then partitioned between EtOAc and 1 M citric acid. The organic layer was dried (Na2SO4) and concentrated. The residue was dissolved in DMF (1 mL) and treated with EDC (25 mg, 0.13 mmol), HOBt (15 mg, 0.11 mmol), and 1,2-phenylenediamine (25 mg, 0.23 mmol), then stirred overnight. The reaction mixture was partitioned between CH2Cl2 and sat'd NaHCO3, dried (Na2SO4), concentrated and finally triturated with ether to provide the desired product: 1H NMR (600 MHz, DMSO-^6) delta 9.75 (s, 1 H), 8.13 (s, 1 H), 7.77 (d, J = 8.8 Hz, 1 H), 7.45 (d, J = 2.1 Hz, 1 H), 7.36 (m, 5 H), 7.32 (m, 1 H), 7.17 (dd, J = 9.1, 2.3 Hz, 1 H), 6.95 (t, J = 7.8 Hz, 1 H), 6.75 (dd, J = 9.4, 1.2 Hz, 1 H), 6.57 (t, J = 7.6 Hz, 1 H), 5.10 (s, 2 H), 4.93 (s, 2 H), 3.55 (br, 4 H), 3.25 (br, 4 H); MS cal'd 487 (MH+), exp 487 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In toluene; at 70℃; for 16h; | [00199] To a suspension of Intermediate 33 A (50 mg, 0.167 mmol) and Pd2(dba)3 (15.25 mg, 0.017 mmol) in toluene (2 mL) was added xantphos (28.9 mg, 0.050 mmol), benzyl piperazine-l-carboxylate (36.7 mg, 0.167 mmol), followed by sodium tert-butoxide (48.0 mg, 0.500 mmol). The reaction mixture was stirred at 70 C for 16 h, and then filtered. The filtrate was concentrated and purified on ISCO using a 15 min gradient from 0 to 100% EtOAc in hexane to give Intermediate 33B (70 mg,0.159 mmol, 96 % yield). LC-MS (ESI) m/z 440.1 (M+H), RT = 2.27 min (Method B). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With palladium diacetate; caesium carbonate; XPhos; In toluene; at 105℃;Inert atmosphere; | Into a 100-mL round-bottom flask, purged and maintained with an inert atmosphere of nitrogen, was added <strong>[120157-97-3]tert-butyl (4-bromophenethyl)carbamate</strong> (4,00 g, 13.3 mmol) and anhydrous toluene (50 mL). To the resulting solution was added benzyl piperazine-1- carboxylate (3.53 g, 16.0 mmol), Pd(OAc)2 (300 mg, 1.34 mmol), XPhos (1.28 g, 2.69 mmol), and CsiCO, (13.1 g, 40.0 mmol). The reaction mixture was stirred overnight at 105 C in an oil bath and then cooled to RT and quenched by the addition of H20 (200 mL). The resulting mixture was extracted with ethyl acetate (2 x 50 mL). The combined organic layers were washed with brine (1 x 200 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified by FCC eluting with ethyl acetate/petroleum ether (PE/EA=3 : 1) to afford benzyl 4-(4-(2-((fert-butoxycarbonyl)amino)ethyl)phenyl)piperazine-l- carboxylate as a yellow solid (5 g, 85%), LCMS (ESI, m/z) 440 [M+H]+ |
85% | With palladium diacetate; caesium carbonate; XPhos; In toluene; at 105℃;Inert atmosphere; | (0937) [00331] Into a 100-mL round-bottom flask, purged and maintained under an inert atmosphere of nitrogen, was added fe/t~buty (4~bromophenethyl)carbarnate (4.00 g, 13.3 mmol) dissolved in anhydrous toluene (50-mL). To the resulting solution was added benzyl piperazine-1- carboxylate (3.53 g, 16.0 mmol), Pd(OAc)2 (0.300 g, 1.34 mmol), XPhos (1.28 g, 2.69 mmol), and CS2CO3 (13.1 g, 40.0 mmol). The reaction mixture was stirred overnight at 105 C in an oil bath and then cooled to RT and quenched with H2O (200 mL). The resulting mixture was extracted with ethyl acetate (2 x 50 mL). The combined organic layers were washed with brine (1 x 200 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The resulting crude product was purified by FCC eluting with ethyl acetate/petroleum ether (PE/EA=3: 1) to afford benzyl 4-(4-(2-((feri-butoxycarbonyl)amino)ethyl)phenyl) piperazine-1- carboxylate as a yellow solid (5 g, 85%), LCMS (ESI, m/z): 440 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; | To a solution of 2-(2-hydroxyethoxy)ethyl 4-methylbenzenesulfonate (2.7 g, 10.4 mmol) and benzyl piperazine-1-carboxylate (2.3 g, 10.4 mmol) in DMF (10 mL) was added K2CO3 (2.86 g, 20.8 mmol). The solution was stirred at 80oC overnight. The mixture was extracted with ethyl acetate (50 mL × 2). The organic phase was washed with water (10 mL) and brine (8 mL). The organic layer was dried (Na2SO4), filtered and concentrated under reduced pressure to afford the crude Benzyl 4-(2-(2-hydroxyethoxy)ethyl)piperazine-1-carboxylate (4.5 g), which was used in the next reaction without further purification |
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