1-methylpyrrolidine-2-carbaldehyde

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-[4-[[3-Chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl]-2-diethoxyphosphoryl-acetamide 1d (3 g, 4.40 mmol) was dissolved in 30 mL of tetrahydrofuran in a dry ice bath, followed by dropwise addition of a solution of lithium bis(trimethylsilyl)amide (1 M) in toluene (9.6 mL, 8.80 mmol). After the mixture was stirred for 30 minutes, a solution of 1-methylpyrrolidine-2-carbaldehyde 10e (1 g, 8.80 mmol) in 5 mL of tetrahydrofuran was added dropwise. The reaction mixture was stirred for another 30 minutes, then warmed up to room temperature and stirred for 24 hours. The reaction mixture was concentrated under reduced pressure and the resulting residue was purified by silica gel column chromatography with elution system A to obtain the title compound (E)-N-[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl]-3-(1-methylpyrrolidin-2-yl)prop-2-enamide 10 (500 mg, yield 20.8%) as a yellow solid. The reaction mixture was stirred for another 30 minutes stirred for 24 hours The reaction mixture was concentrated under reduced pressure the resulting residue was purified by silica gel column chromatography with elution system

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-[4-[[3-Chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl]-2-diethoxyphosphoryl-acetamide 1d (3 g, 4.40 mmol) was dissolved in 30 mL of tetrahydrofuran in a dry ice bath, followed by dropwise addition of a solution of lithium bis(trimethylsilyl)amide (1 M) in toluene (9.6 mL, 8.80 mmol). After the mixture was stirred for 30 minutes, a solution of 1-methylpyrrolidine-2-carbaldehyde 10e (1 g, 8.80 mmol) in 5 mL of tetrahydrofuran was added dropwise. The reaction mixture was stirred for another 30 minutes, then warmed up to room temperature and stirred for 24 hours. The reaction mixture was concentrated under reduced pressure and the resulting residue was purified by silica gel column chromatography with elution system A to obtain the title compound (E)-N-[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl]-3-(1-methylpyrrolidin-2-yl)prop-2-enamide 10 (500 mg, yield 20.8%) as a yellow solid. The reaction mixture was stirred for another 30 minutes stirred for 24 hours The reaction mixture was concentrated under reduced pressure the resulting residue was purified by silica gel column chromatography with elution system