Hydrochloric Acid → 4-(2,3-dihydro-1H-indol-6-ylamino)-6-methoxy-7-(3-pyridin-4-yl-propoxy)-quinoline-3-carbonitrile

Participants

Reaction Steps

To a 0° C. solution consisting of 2 ml of chloroform, 1 ml of tetrahydrofurane, 167 mg (0.64 mM) of triphenyl phosphine, 52 μl (0.40 mM) of 4-hydroxypropylpyridine and 107 mg (0.32 mM) of the 4-(2,3-dihydro-1H-indol-6-ylamino)-7-hydroxy-6-methoxy-quinoline-3-carbonitrile, was slowly added 101 μL (0.64 mM) of DEAD. The reaction was allowed to run at 0° C. for 15 min and then allowed to warm to room temperature. The heterogeneous solution was allowed to stir at room temperature for 7 hour. TCL and ES MS showed no signs of product formation. An additional 1 ml of chloroform and 500 mL of tetrahydrofurane was added and the reaction was refluxed for 14 hours. Once again no signs of product formation were seen. The volume of the reaction was reduced to 1 ml by heating and then brought up to 4 ml by addition of tetrahydrofurane. Once the reaction had cooled to room temperature, and additional 80 mg (0.32 mM) of triphenyl phosphine, 25 μl (0.20 mM) of 4-hydroxypropylpyridine was added followed by the slow addition of 50 μL (0.32 mM) of DEAD. The reaction quickly turned to a clear brown solution. After six hours at room temperature, TLC and the mass spectrum showed the reaction was complete. To the reaction mixture was added 10 ml of 1N HCl followed by 20 ml of water. The solution was extracted five time with 25 ml portions of chloroform. The water layer was allowed to stand for three hours at room temperature and the resulting brown solid was isolated by filtration. The filtrate was treated with solid sodium bicarbonate until a yellow solid fell from solution. The precipitate was isolated and washed with excess water followed by 1 ml of diethyl ether and dried under vacuum at 80° C. to give 57 mg of 4-(2,3-dihydro-1H-indol-6-ylamino)-6-methoxy-7-(3-pyridin-4-yl-propoxy)-quinoline-3-carbonitrile as a yellow solid: mass spectrum (electrospray, m/e): 452.3 M+H, 226.7 M+2H/2, mp=100-105° C.

Provenance & Evidence