4-(2-AMINO-ETHYL)-PIPERAZINE-1-CARBOXYLIC ACID TERT-BUTYL ESTER

General procedure: A solution of the N-substituted phthalimide (2.00 mmol) and hydrazine hydrate (80percent in water, 2 mL) in ethanol (20 mL) was stirred at 70 °C for 20 h. The mixture was cooled to room temperature, the precipitate was filtered off and the solvent was evaporated in vacuo yielding a residue, which was used without further purificationa A mixture of 2- (5-amino-2- (furan-2-yl) -7H-pyrazolo [4, 3-e] [1, 2, 4] triazolo [1, 5-c] pyrimidin-7-yl) -2-phenylpropanoic acid (60 mg, 0.154 mmol) , the product of Step B (35.3 mg, 0.154 mmol) , HATU (70.6 mg, 0.18 mmol) and DIPEA (40 mg, 0.308 mmol) in DMF (3 mL) was stirred overnight. The reaction mixture was poured into H 2O (15 mL) and extracted with EtOAc (10 mL x 3) . The combined organic layers were washed with brine, dried over Na 2SO 4, concentrated and purified by prep-TLC (petroleum ether/EtOAc=1: 2) to give the target compound (34 mg, 36.8%) as a white solid. MS: M/e 601 (M+1) +.General procedure: One pot method was adopted for synthesis of 2a-k. Firstly, in a50 ml round-bottom flask, appropriate primary amine 1a-k(3.125 mmol), triethylamine (6.25 mmol) and CS2 (6.25 mmol) weredissolved in ethanol (15 mL). The reaction mixture was stirred for3 h at room temperature. Upon completion of the reaction, di-tertbutyldecarbonate (8.5 mmol), dissolved in absolute ethanol, wasadded followed by the immediate addition of a catalytic amount of4-dimethylaminopyridine (0.425 mmol). After the reaction mixturewas kept for further 30 min at room temperature, the solvent wasdistilled off under reduced pressure, and the residue was purifiedby column chromatography (petroleum ether/ethyl acetate= 4:1)to afford the corresponding 2a-k in 48-66% yield.To a stirred suspension of tert-butyl 4-(2-aminoethy|l)piperazine-I-carboxylate (CAS: 192130-34-0) (297 mg, 1.68 mmol) and intermediate 35 (600 mg, 1.29 mmol) in DMF (4 mL) at room temperature were added HOBT (350 mg, 2.59 mmol), EDCI (498 mg, 5 2.59 mmol) and DIPEA (502 mg, 3.89 mmol). The reaction was stirred at room temperature overnight. The reaction mixture was diluted with saturated aqueous NH4Cl (50 mL), solid precipitated. The resulting mixture was filtered. The filter cake was collected and dried to give intermediate 103 (600 mg, 68% yield).

Molecular Weight:229.32
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:4
Exact Mass:229.17902698
Monoisotopic Mass:229.17902698
Topological Polar Surface Area:58.8
Heavy Atom Count:16
Complexity:230
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes