1-BOC-2-(2-氯乙酰基)吡咯烷

反应条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 4-Bromo-benzamidine (0.202 g) and potassium carbonate (0.237 g) in H2O (0.286 mL) and THF (1.1 mL) was heated to 65° C. 2-(2-Chloro-acetyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.106 g) in THF (0.7 mL) was added over 1 hour and reaction mixture heated at 65° C. for 18 hours. Reaction mixture was concentrated to ˜0.5 mL and extracted with ethyl acetate. Organic layer was washed with H2O, brine and dried (MgSO4), concentrated and purified by flash column chromatography (silica gel, 20 to 100% ethyl acetate/hexanes) to give 2-[2-(4-Bromo-phenyl)-3H-imidazol-4-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (0.075 g) as an orange film: LCMS-ESI−: calc'd for C18H23BrN3O2: 393.30 (M+H+). Found: 391.8, 393.83 (M+H+). reaction mixture heated at 65° C. for 18 hours Reaction mixture was concentrated to ˜0.5 mL extracted with ethyl acetate Organic layer was washed with H2O, brine dried (MgSO4) concentrated purified by flash column chromatography (silica gel, 20 to 100% ethyl acetate/hexanes)

反应条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 4-Bromo-benzamidine (0.202 g) and potassium carbonate (0.237 g) in H2O (0.286 mL) and THF (1.1 mL) was heated to 65° C. 2-(2-Chloro-acetyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.106 g) in THF (0.7 mL) was added over 1 hour and reaction mixture heated at 65° C. for 18 hours. Reaction mixture was concentrated to ˜0.5 mL and extracted with ethyl acetate. Organic layer was washed with H2O, brine and dried (MgSO4), concentrated and purified by flash column chromatography (silica gel, 20 to 100% ethyl acetate/hexanes) to give 2-[2-(4-Bromo-phenyl)-3H-imidazol-4-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (0.075 g) as an orange film: LCMS-ESI−: calc'd for C18H23BrN3O2: 393.30 (M+H+). Found: 391.8, 393.83 (M+H+). reaction mixture heated at 65° C. for 18 hours Reaction mixture was concentrated to ˜0.5 mL extracted with ethyl acetate Organic layer was washed with H2O, brine dried (MgSO4) concentrated purified by flash column chromatography (silica gel, 20 to 100% ethyl acetate/hexanes)

反应条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 4-Bromo-benzamidine (0.202 g) and potassium carbonate (0.237 g) in H2O (0.286 mL) and THF (1.1 mL) was heated to 65° C. 2-(2-Chloro-acetyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.106 g) in THF (0.7 mL) was added over 1 hour and reaction mixture heated at 65° C. for 18 hours. Reaction mixture was concentrated to ˜0.5 mL and extracted with ethyl acetate. Organic layer was washed with H2O, brine and dried (MgSO4), concentrated and purified by flash column chromatography (silica gel, 20 to 100% ethyl acetate/hexanes) to give 2-[2-(4-Bromo-phenyl)-3H-imidazol-4-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (0.075 g) as an orange film: LCMS-ESI−: calc'd for C18H23BrN3O2: 393.30 (M+H+). Found: 391.8, 393.83 (M+H+). reaction mixture heated at 65° C. for 18 hours Reaction mixture was concentrated to ˜0.5 mL extracted with ethyl acetate Organic layer was washed with H2O, brine dried (MgSO4) concentrated purified by flash column chromatography (silica gel, 20 to 100% ethyl acetate/hexanes)

反应条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 4-Bromo-benzamidine (0.202 g) and potassium carbonate (0.237 g) in H2O (0.286 mL) and THF (1.1 mL) was heated to 65° C. 2-(2-Chloro-acetyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.106 g) in THF (0.7 mL) was added over 1 hour and reaction mixture heated at 65° C. for 18 hours. Reaction mixture was concentrated to ˜0.5 mL and extracted with ethyl acetate. Organic layer was washed with H2O, brine and dried (MgSO4), concentrated and purified by flash column chromatography (silica gel, 20 to 100% ethyl acetate/hexanes) to give 2-[2-(4-Bromo-phenyl)-3H-imidazol-4-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (0.075 g) as an orange film: LCMS-ESI−: calc'd for C18H23BrN3O2: 393.30 (M+H+). Found: 391.8, 393.83 (M+H+). reaction mixture heated at 65° C. for 18 hours Reaction mixture was concentrated to ˜0.5 mL extracted with ethyl acetate Organic layer was washed with H2O, brine dried (MgSO4) concentrated purified by flash column chromatography (silica gel, 20 to 100% ethyl acetate/hexanes)

反应条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 4-Bromo-benzamidine (0.202 g) and potassium carbonate (0.237 g) in H2O (0.286 mL) and THF (1.1 mL) was heated to 65° C. 2-(2-Chloro-acetyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.106 g) in THF (0.7 mL) was added over 1 hour and reaction mixture heated at 65° C. for 18 hours. Reaction mixture was concentrated to ˜0.5 mL and extracted with ethyl acetate. Organic layer was washed with H2O, brine and dried (MgSO4), concentrated and purified by flash column chromatography (silica gel, 20 to 100% ethyl acetate/hexanes) to give 2-[2-(4-Bromo-phenyl)-3H-imidazol-4-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (0.075 g) as an orange film: LCMS-ESI−: calc'd for C18H23BrN3O2: 393.30 (M+H+); Found: 391.8, 393.83 (M+H+). reaction mixture heated at 65° C. for 18 hours Reaction mixture was concentrated to ˜0.5 mL extracted with ethyl acetate Organic layer was washed with H2O, brine dried (MgSO4) concentrated purified by flash column chromatography (silica gel, 20 to 100% ethyl acetate/hexanes)

反应条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 4-Bromo-benzamidine (0.202 g) and potassium carbonate (0.237 g) in H2O (0.286 mL) and THF (1.1 mL) was heated to 65° C. 2-(2-Chloro-acetyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.106 g) in THF (0.7 mL) was added over 1 hour and reaction mixture heated at 65° C. for 18 hours. Reaction mixture was concentrated to ˜0.5 mL and extracted with ethyl acetate. Organic layer was washed with H2O, brine and dried (MgSO4), concentrated and purified by flash column chromatography (silica gel, 20 to 100% ethyl acetate/hexanes) to give 2-[2-(4-Bromo-phenyl)-3H-imidazol-4-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (0.075 g) as an orange film: LCMS-ESI−: calc'd for C18H23BrN3O2: 393.30 (M+H+). Found: 391.8, 393.83 (M+H+). reaction mixture heated at 65° C. for 18 hours Reaction mixture was concentrated to ˜0.5 mL extracted with ethyl acetate Organic layer was washed with H2O, brine dried (MgSO4) concentrated purified by flash column chromatography (silica gel, 20 to 100% ethyl acetate/hexanes)

反应条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 4-Bromo-benzamidine (0.202 g) and potassium carbonate (0.237 g) in H2O (0.286 mL) and THF (1.1 mL) was heated to 65° C. 2-(2-Chloro-acetyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.106 g) in THF (0.7 mL) was added over 1 hour and reaction mixture heated at 65° C. for 18 hours. Reaction mixture was concentrated to ˜0.5 mL and extracted with ethyl acetate. Organic layer was washed with H2O, brine and dried (MgSO4), concentrated and purified by flash column chromatography (silica gel, 20 to 100% ethyl acetate/hexanes) to give 2-[2-(4-Bromo-phenyl)-3H-imidazol-4-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (0.075 g) as an orange film: LCMS-ESI−: calc'd for C18H23BrN3O2: 393.30 (M+H+). Found: 391.8, 393.83 (M+H+). reaction mixture heated at 65° C. for 18 hours Reaction mixture was concentrated to ˜0.5 mL extracted with ethyl acetate Organic layer was washed with H2O, brine dried (MgSO4) concentrated purified by flash column chromatography (silica gel, 20 to 100% ethyl acetate/hexanes)

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

实验步骤: An ethanol (20 mL) solution of tert-butyl 2-(2-chloroacetyl)pyrrolidine-1-carboxylate (1.08 g, 4.4 mol) and thiourea (334 mg, 4.4 mmol) was stirred at 55 C for 70 hours. Upon completion of the condensation, the solution was evaporated. The solid was dissolved in CH2Cl2 (100 mL). It was washed with dilute NaHCO3 solution, dried and evaporated. Recrystallization from CH2Cl2/hexane afforded tert-butyl 2-(2-aminothiazol-4-yl)pyrrolidine-1-carboxylate. 1H NMR (400 MHz, CDCl3): mixture of rotamers: δ 8.81 (s, 2H, br), 6.22 and 6.15 (2s, 1H), 4.84 and 4.78 (2s, 1H), 3.62 and 3.44 (2m, 2H), 2.4-1.8 (m, 4H), 1.46 and 1.36 (2s, 9H). MS (ES+): M/Z 270 (M+H)+, 170 (M−C5H8O2)+. Upon completion of the condensation the solution was evaporated The solid was dissolved in CH2Cl2 (100 mL) It was washed with dilute NaHCO3 solution dried evaporated Recrystallization from CH2Cl2/hexane

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

实验步骤: To a solution of tert-butyl 2-(2-chloroacetyl)pyrrolidine-1-carboxylate (5 g, 20.24 mmol) in 200 mL of acetone was added 3 g (20.24 mmol) of NaI. The reaction was let to stir at room temperature for 18 h. The reaction was monitored by TLC (20% EtOAc/hexanes, the plate was developed by KMnO4 stain). The reaction mixture was filtered over celite, concentrated and dried to afford tert-butyl 2-(2-iodoacetyl)pyrrolidine-1-carboxylate (8 g, 99% yield). 1H NMR (CDCl3): δ 1.45 (d, 9H), 1.99 (s, 3H), 2.20 (m, 1H), 3.50 (m, 2H), 4.90 (m, 2H), 4.50 (m, 1H). The reaction mixture was filtered over celite concentrated dried

反应条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 4-Bromo-benzamidine (0.202 g) and potassium carbonate (0.237 g) in H2O (0.286 mL) and THF (1.1 mL) was heated to 65° C. 2-(2-Chloro-acetyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.106 g) in THF (0.7 mL) was added over 1 hour and reaction mixture heated at 65° C. for 18 hours. Reaction mixture was concentrated to ˜0.5 mL and extracted with ethyl acetate. Organic layer was washed with H2O, brine and dried (MgSO4), concentrated and purified by flash column chromatography (silica gel, 20 to 100% ethyl acetate/hexanes) to give 2-[2-(4-Bromo-phenyl)-3H-imidazol-4-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (0.075 g) as an orange film: LCMS-EST: calc'd for C18H23BrN3O2: 393.30 (M+H+). Found: 391.8, 393.83 (M+H+). reaction mixture heated at 65° C. for 18 hours Reaction mixture was concentrated to ˜0.5 mL extracted with ethyl acetate Organic layer was washed with H2O, brine dried (MgSO4) concentrated purified by flash column chromatography (silica gel, 20 to 100% ethyl acetate/hexanes)

反应条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 4-Bromo-benzamidine (0.202 g) and potassium carbonate (0.237 g) in H2O (0.286 mL) and THF (1.1 mL) was heated to 65° C. 2-(2-Chloro-acetyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.106 g) in THF (0.7 mL) was added over 1 hour and reaction mixture heated at 65° C. for 18 hours. Reaction mixture was concentrated to ˜0.5 mL and extracted with ethyl acetate. Organic layer was washed with H2O, brine and dried (MgSO4), concentrated and purified by flash column chromatography (silica gel, 20 to 100% ethyl acetate/hexanes) to give 2-[2-(4-Bromo-phenyl)-3H-imidazol-4-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (0.075 g) as an orange film: LCMS-ESI−: calc'd for C18H23BrN3O2: 393.30 (M+H+). Found: 391.8, 393.83 (M+H+). reaction mixture heated at 65° C. for 18 hours Reaction mixture was concentrated to ˜0.5 mL extracted with ethyl acetate Organic layer was washed with H2O, brine dried (MgSO4) concentrated purified by flash column chromatography (silica gel, 20 to 100% ethyl acetate/hexanes)