1-氯-4-异氰基苯

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

实验步骤: 4-chlorobenzenamine 12.7 g (0.1 mol), and 470 mg BnEt3NCl was suspended in the mixture of 200 ml DCM, 200 ml CH3C1 and 200 ml 50% KOH (aq.), then was stirred at room temperature for 2 h. The organic phase was separated, washed with water (500 ml), dried with Na2SO4 and concentrated to afford yellow oil, which was purified by chromatography; 1-chloro-4-isocyanobenzene 500 mg, 2-hydroxynaphthalene-1,4-dione 635 mg (1.0 eq) and Paraformaldehyde 109 mg (1.0 eq) was dissolved in 30 ml toluene, stirred and refluxed under N2 for 4 h. After removing all solvents under reduced pressure, the residue was purified by chromatography to afford 2-(4-chlorophenylamino)naphtho[2,3-b]furan-4,9-dione as black solid. 1H NMR (300 MHz, DMSO) δ6.39 (s, 1H); 7.24˜7.29 (m, 2H); 7.41˜7.43 (dd, 2H); 7.54 (br, 1H); 7.69˜7.73 (t, 1H); 7.78˜7.82 (t, 1H); 8.13˜8.17 (t, 3H) ppm. MS-ESI: cal. 323; found: 346 (M+Na). The organic phase was separated washed with water (500 ml) dried with Na2SO4 concentrated to afford yellow oil, which was purified by chromatography stirred refluxed under N2 for 4 h After removing all solvents under reduced pressure the residue was purified by chromatography

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

实验步骤: To a solution of 3,3-difluoropyrrolidine hydrochloride (129 mg, 0.90 mmol, Sigma-Aldrich) in methanol (3 mL) was added formaldehyde (37% aqueous) (0.067 mL, 0.90 mmol) and triethylamine (0.139 mL, 1.00 mmol). The reaction mixture was shaken at room temperature for 2 hours. To the reaction mixture was added 4-chlorophenyl isocyanide (138 mg, 1.00 mmol) and trimethylsilylazide (0.133 mL, 1.00 mmol). The reaction mixture was shaken at room temperature for a further 18 hours. The reaction mixture was shaken at room temperature for a further 18 hours

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

实验步骤: To a solution of (cis)-2,6-dimethylmorpholine (104 mg, 0.900 mmol, Alfa Aesar, Ward Hill, USA) in methanol (3 mL) was added formaldehyde (37% aqueous) (0.067 mL, 0.900 mmol). The reaction mixture was shaken at room temperature for 2 hours. To the reaction mixture was added 4-chlorophenyl isocyanide (138 mg, 1 mmol) and trimethylsilylazide (0.133 mL, 1.00 mmol). The reaction mixture was shaken at room temperature for a further 18 hours. The reaction mixture was shaken at room temperature for a further 18 hours

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

实验步骤: Methyl 4-formylmethylbenzoate (56.3 mg, 0.316 mmol, 4-chlorophenyl isocyanide (43.5 mg, 0.316 mmol), 1-(2,4-dimethoxyphenyl)methanamine (56.9 μL, 0.379 mmol) and benzoic acid (38.6 mg, 0.316 mmol) were dissolved in 100 μL of trifluoroethanol and heated at 50° C. for 2 hours. The reaction mixture was diluted with 2 mL of methanol and purified by reversed phase HPLC to afford the desired product. MS cal'd 587.2 (MH+), exp 587.2 (MH+). purified by reversed phase HPLC

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

实验步骤: Methyl 4-formylmethylbenzoate (52.3 mg, 0.294 mmol), 4-chlorophenyl isocyanide (40.4 mg, 0.294 mmol), N-methylpiperazine (39.1 μL, 0.352 mmol) and AcOH (16.6 μL, 0.294 mmol) were dissolved in 100 μL of trifluoroethanol and heated at 50° C. for 3 hours. The reaction mixture was diluted with 2 mL of methanol and purified by reverse phase HPLC to afford the desired product. MS cal'd 416.2 (MH+), exp 416.2 (MH+). purified by reverse phase HPLC

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

实验步骤: Ethyl 5-formylthiophene-2-carboxylate (0.50 g, 2.71 mmol) was made 2.25 M in anhydrous trifluoroethanol and to this stirring solution was added N-methylpiperazine (0.33 g, 3.26 mmol), 1-chloro-4-isocyanobenzene (0.45 g, 3.26 mmol) and acetic acid (0.20 g, 3.26 mmol). The resulting mixture was stirred at ambient temperature overnight. The reaction mixture was concentrated in vacuo then purified by MPLC to give the desired product. MS: cal'd 422, 424 (MH+), exp 422, 424 (MH+). The reaction mixture was concentrated in vacuo then purified by MPLC

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

实验步骤: Methyl 4-(3-oxopropyl)benzoate (43.5 mg, 0.226 mmol), 4-chlorophenyl isocyanide (43.5 mg, 0.316 mmol), N-methylpiperazine (40.0 μL, 0.36 mmol) and AcOH (20.0 μL, 0.36 mmol) were dissolved in 100 μL of trifluoroethanol and heated at 50° C. for 3 hours. The reaction mixture was diluted with 2 mL of methanol and purified by reversed phase HPLC to afford the desired product. MS cal'd 430.2 (MH+), exp 430.1 (MH+). purified by reversed phase HPLC

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

实验步骤: 4-chlorobenzenamine 12.7 g (0.1 mol), and 470 mg BnEt3NCl was suspended in the mixture of 200 ml DCM, 200 ml CH3C1 and 200 ml 50% KOH (aq.), then was stirred at room temperature for 2 h. The organic phase was separated, washed with water (500 ml), dried with Na2SO4 and concentrated to afford yellow oil, which was purified by chromatography; 1-chloro-4-isocyanobenzene 500 mg, 2-hydroxynaphthalene-1,4-dione 635 mg (1.0 eq) and Paraformaldehyde 109 mg (1.0 eq) was dissolved in 30 ml toluene, stirred and refluxed under N2 for 4 h. After removing all solvents under reduced pressure, the residue was purified by chromatography to afford 2-(4-chlorophenylamino)naphtho[2,3-b]furan-4,9-dione as black solid. 1H NMR (300 MHz, DMSO) δ6.39 (s, 1H); 7.24˜7.29 (m, 2H); 7.41˜7.43 (dd, 2H); 7.54 (br, 1H); 7.69˜7.73 (t, 1H); 7.78˜7.82 (t, 1H); 8.13˜8.17 (t, 3H) ppm. MS-ESI: cal. 323; found: 346 (M+Na). The organic phase was separated washed with water (500 ml) dried with Na2SO4 concentrated to afford yellow oil, which was purified by chromatography stirred refluxed under N2 for 4 h After removing all solvents under reduced pressure the residue was purified by chromatography

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

实验步骤: To a solution of 3,3-difluoropyrrolidine hydrochloride (129 mg, 0.90 mmol, Sigma-Aldrich) in methanol (3 mL) was added formaldehyde (37% aqueous) (0.067 mL, 0.90 mmol) and triethylamine (0.139 mL, 1.00 mmol). The reaction mixture was shaken at room temperature for 2 hours. To the reaction mixture was added 4-chlorophenyl isocyanide (138 mg, 1.00 mmol) and trimethylsilylazide (0.133 mL, 1.00 mmol). The reaction mixture was shaken at room temperature for a further 18 hours. The reaction mixture was shaken at room temperature for a further 18 hours

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

实验步骤: To a solution of (cis)-2,6-dimethylmorpholine (104 mg, 0.900 mmol, Alfa Aesar, Ward Hill, USA) in methanol (3 mL) was added formaldehyde (37% aqueous) (0.067 mL, 0.900 mmol). The reaction mixture was shaken at room temperature for 2 hours. To the reaction mixture was added 4-chlorophenyl isocyanide (138 mg, 1 mmol) and trimethylsilylazide (0.133 mL, 1.00 mmol). The reaction mixture was shaken at room temperature for a further 18 hours. The reaction mixture was shaken at room temperature for a further 18 hours