顺式-3,4-二羟基吡咯烷盐酸盐

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (3R,4S)-3,4-Dihydroxypyrrolidine hydrochloride (the cis, or meso isomer, 1.79 mmol) and [(5-chloro-1H-indole-2-carbonyl)-amino]-acetic acid (0.85 mmol) were coupled according to procedure A (1:1 CH2Cl2/DMF reaction solvent) with the following workup: the reaction mixture was concentrated, the residue suspended in 10 ml EtOAc and 10 ml 2 N NaOH, the solids filtered and washed successively with aqueous 1 N NaOH, EtOAc, aqueous 1 N HCl, H2O, and ether. This washing sequence was repeated and the resulting solids were suspended in EtOAc, stirred for 1 hour, filtered and dried: Yield 252 mg, 88%; HPLC (60/40) 2.33 minutes (93%); TSPMS 338/340 (MH+, 100%); the reaction mixture was concentrated 10 ml 2 N NaOH, the solids filtered washed successively with aqueous 1 N NaOH, EtOAc, aqueous 1 N HCl, H2O, and ether filtered dried HPLC (60/40) 2.33 minutes (93%)

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A suspension of [6-(4,4-dimethylcyclohexyl)-2-methylthieno[2,3-d]pyrimidin-4-yl]methyl methanesulfonate (100 mg), cis-pyrrolidine-3,4-diol hydrochloride (57 mg), and K2CO3 (75 mg) in DMF (3 mL) was stirred at 50° C. for 12 hours. The reaction mixture was cooled to room temperature, and water was added thereto, followed by extraction with EtOAc. The organic layer was dried over MgSO4 and then concentrated under reduced pressure. The residue was purified by silica gel column (chloroform/MeOH). The obtained purified product was suspended in IPE, and the precipitate was collected by filtration to obtain cis-1-{[6-(4,4-dimethylcyclohexyl)-2-methylthieno[2,3-d]pyrimidin-4-yl]methyl}pyrrolidine-3,4-diol (9 mg). The reaction mixture was cooled to room temperature followed by extraction with EtOAc The organic layer was dried over MgSO4 concentrated under reduced pressure The residue was purified by silica gel column (chloroform/MeOH) The obtained purified product the precipitate was collected by filtration

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (3R,4S)-3,4-Dihydroxypyrrolidine hydrochloride (the cis, or meso isomer, 1.79 mmol) and [(5-chloro-1H-indole-2-carbonyl)-amino]-acetic acid (0.85 mmol) were coupled according to procedure A (1:1 CH2Cl2 /DMF reaction solvent) with the following workup: the reaction mixture was concentrated, the residue suspended in 10 ml EtOAc and 10 ml 2N NaOH, the solids filtered and washed successively with .aqueous 1N NaOH, EtOAc, aqueous 1N HCl, H2O, and ether. This washing sequence was repeated and the resulting solids were suspended in EtOAc, stirred for 1 hour, filtered and dried: Yield 252 mg, 88%; HPLC (60/40) 2.33 minutes (93%); TSPMS 338/340 (MH+, 100%); the reaction mixture was concentrated 10 ml 2N NaOH, the solids filtered washed successively with .aqueous 1N NaOH, EtOAc, aqueous 1N HCl, H2O, and ether filtered dried HPLC (60/40) 2.33 minutes (93%)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (3R,4S)-3,4-Dihydroxypyrrolidine hydrochloride (the cis, or meso isomer, 1.79 mmol) and [(5-chloro-1H-indole-2-carbonyl)-amino]-acetic acid (0.85 mmol) were coupled according to procedure A (1:1 CH2Cl2/DMF reaction solvent) with the following workup: the reaction mixture was concentrated, the residue suspended in 10 ml EtOAc and 10 ml 2 N NaOH, the solids filtered and washed successively with aqueous 1 N NaOH, EtOAc, aqueous 1 N HCl, H2O, and ether. This washing sequence was repeated and the resulting solids were suspended in EtOAc, stirred for 1 hour, filtered and dried: Yield 252 mg, 88%; HPLC (60/40) 2.33 minutes (93%); TSPMS 338/340 (MH+, 100%); the reaction mixture was concentrated 10 ml 2 N NaOH, the solids filtered washed successively with aqueous 1 N NaOH, EtOAc, aqueous 1 N HCl, H2O, and ether filtered dried HPLC (60/40) 2.33 minutes (93%)