4-二乙氨基-but-2-壬酸

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: n-Butyl lithium in hexane (54 mL, 2.5M in n-hexane) was slowly added to 1-diethylamino-2-propyne (15 g, 135 mmol) in 60 mL of tetrahydrofuran under nitrogen. The mixture was stirred for 1 hr at −78° C., then dry carbon dioxide was passed through overnight. The resulting solution was poured into water and washed with ethyl acetate. The aqueous layer was evaporated under reduced pressure to give the crude acid. The dry acid was dissolved in methanol, and the insoluble salt was removed via filtration. The filtrate was collected and dried in vacuo to give 9.2 g of 4-diethylamino-but-2-ynoic acid: mass spectrum (m/e):M+H 156. washed with ethyl acetate The aqueous layer was evaporated under reduced pressure to give the crude acid the insoluble salt was removed via filtration The filtrate was collected dried in vacuo

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: n-Butyl lithium in hexane (54 mL, 2.5M in n-hexane) was slowly added to 1-diethylamino-2-propyne (15 g, 135 mmol) in 60 mL of tetrahydrofuran under nitrogen. The mixture was stirred for 1 hr at −78° C., then dry carbon dioxide was passed through overnight. The resulting solution was poured into water and washed with ethyl acetate. The aqueous layer was evaporated under reduced pressure to give the crude acid. The dry acid was dissolved in methanol, and the insoluble salt was removed via filtration. The filtrate was collected and dried in vacuo to give 9.2 g of 4-diethylamino-but-2-ynoic acid: mass spectrum (m/e):M+H 156. washed with ethyl acetate The aqueous layer was evaporated under reduced pressure to give the crude acid the insoluble salt was removed via filtration The filtrate was collected dried in vacuo

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

实验步骤: Isobutyl chloroformate (0.061 g, 0.448 mmol) was dropwise added into an ice cold solution of 4-diethylamino-2-butynoic acid (0.104 g, 0.672 mmol) and N-methylmorpholine (0.068 g, 0.672 mmol) in 10 mL of tetrahydrofuan under N2. After stirring for 30 min, a solution of 0.1 g (0.32 mmol) of 6-amino-4-[(3-chloro-4-fluorophenyl)-amino]-3-quinolinecarbonitrile in 1.5 mL of pyridine was added dropwise and the mixture was stirred at 0° C. for 1.5 hr. The reaction was quenched with ice water, poured into saturated sodium bicarbonate and brine, and extracted with ethyl acetate. The ethyl acetate layer was concentrated and purified by thin-layer chromatography eluted with 15% methanol in ethyl acetate. The product was collected, and dried in vacuo to give 0.046 g (32%) of light brown solid; ESMS m/z 450.2, (M+H+); mp 117-120° C. the mixture was stirred at 0° C. for 1.5 hr The reaction was quenched with ice water poured into saturated sodium bicarbonate and brine extracted with ethyl acetate The ethyl acetate layer was concentrated purified by thin-layer chromatography eluted with 15% methanol in ethyl acetate The product was collected dried in vacuo to give 0.046 g (32%) of light brown solid

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

实验步骤: Isobutyl chloroformate (0.261 g, 1.91 mmol) was dropwise added into an ice cold solution of 4-diethylamino-2-butynoic acid (0.456 g, 2.94 mmol) and N-methylmorpholine (0.294 g, 2.94 mmol) in 50 mL of tetrahydrofuan under N2. After stirring for 30 min, a solution of 0.5 g (1.47 mmol) of 6-amino-4-[(3-bromophenyl)amino]-3-quinolinecarbonitrile in 3 mL of pyridine was added dropwise and the mixture was stirred at 0° C. for 2 hr. The reaction was quenched with ice water, poured into saturated sodium bicarbonate and brine, and extracted with ethyl acetate. The ethyl acetate layer was concentrated and purified by thin-layer chromatography eluted with 15% methanol in ethyl acetate. The product was collected, and dried in vacuo to give 0.2 g (28.5%) of pale greenish yellow solid; ESMS m/z 476.2, 478.2 (M+H+); mp 133-135° C. the mixture was stirred at 0° C. for 2 hr The reaction was quenched with ice water poured into saturated sodium bicarbonate and brine extracted with ethyl acetate The ethyl acetate layer was concentrated purified by thin-layer chromatography eluted with 15% methanol in ethyl acetate The product was collected dried in vacuo

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: Isobutyl chloroformate (0.061 g, 0.448 mmol) was dropwise added into an ice cold solution of 4-diethylamino-2-butynoic acid (0.104 g, 0.672 mmol) and N-methyl-morpholine (0.068 g, 0.672 mmol) in 10 mL of tetrahydrofuran under N2. After stirring for 30 min, a solution of 0.1 g (0.32 mmol) of 6-amino-4-[(3-chloro-4-fluorophenyl)amino]-3-quinolinecarbonitrile in 1.5 mL of pyridine was added dropwise and the mixture was stirred at 0° C. for 1.5 hr. The reaction was quenched with ice water, poured into saturated sodium bicarbonate and brine, and extracted with ethyl acetate. The ethyl acetate layer was concentrated and purified by thin-layer chromatography eluted with 15% methanol in ethyl acetate. The product was collected, and dried in vacuo to give 0.046 g (32%) of light brown solid; ESMS m/z 450.2, (M+H+); mp 117-120° C. the mixture was stirred at 0° C. for 1.5 hr The reaction was quenched with ice water poured into saturated sodium bicarbonate and brine extracted with ethyl acetate The ethyl acetate layer was concentrated purified by thin-layer chromatography eluted with 15% methanol in ethyl acetate The product was collected dried in vacuo to give 0.046 g (32%) of light brown solid