but-3-en-1-amine;hydrochloride

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To an ice-cooled solution of 1,3-difluoro-4-nitro-2-vinylbenzene (389 mg, 2.1 mmol) in DMF (8 mL) was added 3-butenylamine hydrochloride (248 mg, 2.31 mmol) and potassium carbonate (0.87 g, 6.3 mmol). The reaction mixture was stirred at RT for 2 h, and then partitioned between water and EtOAc. The aqueous phase was extracted with EtOAc and the combined organic layers were washed with water, followed by brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, eluant 2-4% EtOAc in cyclohexane) affording the title compound as an orange oil (327.6 mg, 66%). LCMS (Method B): RT 4.27 min [M+H]+ 237 partitioned between water and EtOAc The aqueous phase was extracted with EtOAc the combined organic layers were washed with water dried (Na2SO4) concentrated in vacuo The resulting residue was purified by column chromatography (Si—PCC, eluant 2-4% EtOAc in cyclohexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To an ice-cooled solution of 1,3-difluoro-4-nitro-2-vinylbenzene (389 mg, 2.1 mmol) in DMF (8 mL) was added 3-butenylamine hydrochloride (248 mg, 2.31 mmol) and potassium carbonate (0.87 g, 6.3 mmol). The reaction mixture was stirred at RT for 2 h, and then partitioned between water and EtOAc. The aqueous phase was extracted with EtOAc and the combined organic layers were washed with water, followed by brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, eluant 2-4% EtOAc in cyclohexane) affording the title compound as an orange oil (327.6 mg, 66%). LCMS (Method B): RT 4.27 min [M+H]+ 237 partitioned between water and EtOAc The aqueous phase was extracted with EtOAc the combined organic layers were washed with water dried (Na2SO4) concentrated in vacuo The resulting residue was purified by column chromatography (Si—PCC, eluant 2-4% EtOAc in cyclohexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 3-butenylamine hydrochloride (200 mg, 1.12 mmol) and sodium acetate (184 mg, 2.24 mmol) in methanol (15 mL) was added bromomaleimide (200 mg, 1.12 mmol) dropwise in methanol (15 mL). After 10 minutes, solvent was removed in vacuo and purification by flash chromatography (10% ethyl acetate in petroleum ether) afforded the desired compound as a bright yellow waxy solid (142 mg, 0.85 mmol) in 76% yield. δH (500 MHz, CDCl3) 7.10 (s, 1H, NH), 5.77 (tdd, 1H, J=6.9, 10.7 and 17.4, H-2), 5.38 (s, 1H, NH), 5.18-5.15 (m, 2H, H2-1), 4.83 (d, 1H, J=1.3, H-6), 3.24 (t, 2H, J=6.7, H2-4), 2.40 (dtd, 2H, J=1.2, 6.8 and 6.9, H2-3); δC (125 MHz, CDCl3) 171.94 (C═O), 167.45 (C═O), 149.53 (C5), 133.89 (C2), 118.51 (C1), 85.80 (C6), 43.30 (C4), 32.68 (C3); IR (solid, cm−1) 3290 (m), 1703 (m), 1629 (s); MS (ES−) m/z (relative intensity): 165 ([M−H], 100); Exact Mass Calcd for [C8H10N2O2]−H requires m/z 165.0659 Found 165.0664 (ES−); m.p. 68-76° C.; UV (Acetonitrile) ε241=8300 and ε348=6100 cm−1M−1 d3. solvent was removed in vacuo and purification by flash chromatography (10% ethyl acetate in petroleum ether)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To an ice-cooled solution of 1,3-difluoro-4-nitro-2-vinylbenzene (389 mg, 2.1 mmol) in DMF (8 mL) was added 3-butenylamine hydrochloride (248 mg, 2.31 mmol) and potassium carbonate (0.87 g, 6.3 mmol). The reaction mixture was stirred at RT for 2 h, and then partitioned between water and EtOAc. The aqueous phase was extracted with EtOAc and the combined organic layers were washed with water, followed by brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, eluant 2-4% EtOAc in cyclohexane) affording the title compound as an orange oil (327.6 mg, 66%). LCMS (Method B): RT 4.27 min [M+H]+ 237 partitioned between water and EtOAc The aqueous phase was extracted with EtOAc the combined organic layers were washed with water dried (Na2SO4) concentrated in vacuo The resulting residue was purified by column chromatography (Si—PCC, eluant 2-4% EtOAc in cyclohexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of tert-butyl-1-(3-(4-(allyloxy)phenyl)-3-(ethoxyimino)-propanoylimino)-2-(4-(2-bromoacetamido)-3,5-dichlorophenyl)ethylcarbamate (100 mg) in dichloromethane (0.30 mL) at room temperature was added but-3-en-1-amine hydrochloride (45 mg) and diisopropylethylamine (97 μL), and the resulting solution was stirred at room temperature for 2 h. The solvents were removed in vacuo to give the title compound as a white solid, which was used for Step B without purification. retention time: 2.11 min (method A). MS (ESI) (M+H)+ 689.20. The solvents were removed in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of tert-butyl-1-(3-(4-(allyloxy)phenyl)-3-(ethoxyimino)-propanoylimino)-2-(4-(2-bromoacetamido)-3,5-dichlorophenyl)ethylcarbamate (100 mg) in dichloromethane (0.30 mL) at room temperature was added but-3-en-1-amine hydrochloride (45 mg) and diisopropylethylamine (97 μL), and the resulting solution was stirred at room temperature for 2 h. The solvents were removed in vacuo to give the title compound as a white solid, which was used for Step B without purification. retention time: 2.11 min (method A). MS (ESI) (M+H)+ 689.20. The solvents were removed in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of tert-butyl-1-(3-(4-(allyloxy)phenyl)-3-(ethoxyimino)-propanoylimino)-2-(4-(2-bromoacetamido)-3,5-dichlorophenyl)ethylcarbamate (100 mg) in dichloromethane (0.30 mL) at room temperature was added but-3-en-1-amine hydrochloride (45 mg) and diisopropylethylamine (97 μL), and the resulting solution was stirred at room temperature for 2 h. The solvents were removed in vacuo to give the title compound as a white solid, which was used for Step B without purification. retention time: 2.11 min (method A). MS (ESI) (M+H)+ 689.20. The solvents were removed in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 3-butenylamine hydrochloride (200 mg, 1.12 mmol) and sodium acetate (184 mg, 2.24 mmol) in methanol (15 mL) was added bromomaleimide (200 mg, 1.12 mmol) dropwise in methanol (15 mL). After 10 minutes, solvent was removed in vacuo and purification by flash chromatography (10% ethyl acetate in petroleum ether) afforded the desired compound as a bright yellow waxy solid (142 mg, 0.85 mmol) in 76% yield. δH (500 MHz, CDCl3) 7.10 (s, 1H, NH), 5.77 (tdd, 1H, J=6.9, 10.7 and 17.4, H-2), 5.38 (s, 1H, NH), 5.18-5.15 (m, 2H, H2-1), 4.83 (d, 1H, J=1.3, H-6), 3.24 (t, 2H, J=6.7, H2-4), 2.40 (dtd, 2H, J=1.2, 6.8 and 6.9, H2-3); δC (125 MHz, CDCl3) 171.94 (C═O), 167.45 (C═O), 149.53 (C5), 133.89 (C2), 118.51 (C1), 85.80 (C6), 43.30 (C4), 32.68 (C3); IR (solid, cm−1) 3290 (m), 1703 (m), 1629 (s); MS (ES−) m/z (relative intensity): 165 ([M−H], 100); Exact Mass Calcd for [C8H10N2O2]−H requires m/z 165.0659 Found 165.0664 (ES−); m.p. 68-76° C.; UV (Acetonitrile) ε241=8300 and ε348=6100 cm−1M−1 d3. solvent was removed in vacuo and purification by flash chromatography (10% ethyl acetate in petroleum ether)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To an ice-cooled solution of 1,3-difluoro-4-nitro-2-vinylbenzene (389 mg, 2.1 mmol) in DMF (8 mL) was added 3-butenylamine hydrochloride (248 mg, 2.31 mmol) and potassium carbonate (0.87 g, 6.3 mmol). The reaction mixture was stirred at RT for 2 h, and then partitioned between water and EtOAc. The aqueous phase was extracted with EtOAc and the combined organic layers were washed with water, followed by brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, eluant 2-4% EtOAc in cyclohexane) affording the title compound as an orange oil (327.6 mg, 66%). LCMS (Method B): RT 4.27 min [M+H]+ 237 partitioned between water and EtOAc The aqueous phase was extracted with EtOAc the combined organic layers were washed with water dried (Na2SO4) concentrated in vacuo The resulting residue was purified by column chromatography (Si—PCC, eluant 2-4% EtOAc in cyclohexane)