Diisopropylamine → 4-[5-(4-isobutyl piperazin-1-yl)pyridin-2-yl]-3,4-dihydro-2H-quinoxaline-1-carboxylic acid (5-carbamoyladamantan-2-yl)amide

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Reaction Steps

1-[5-(4-Isobutylpiperazin-1-yl)pyridin-2-yl]-1,2,3,4-tetrahydroquinoxaline (0.25 g, 0.71 mmol) is placed in 7 ml of dichloromethane at 0° C. under nitrogen. Triethylamine (0.2 ml, 1.43 mmol) and then triphosgene (0.084 g, 0.28 mmol) are added. The reaction medium is stirred at ambient temperature for 3 h. 7.1 ml of DMF, diisopropylamine (0.31 ml, 1.78 mmol) and then 4-aminoadamantane-1-carboxylic acid amide (0.164 g, 0.71 mmol) are then added. The reaction medium is heated at 50° C. for 18 h under nitrogen. After hydrolysis on 50 ml of ice and extraction with ethyl acetate, the organic phase is washed with water and then with a saturated aqueous sodium chloride solution, dried over MgSO4 and concentrated to dryness. The crude product obtained is chromatographed on silica gel, elution being carried out with an ethyl acetate/methanol/aqueous ammonia gradient in dichloromethane varying from 100/0/0/0 to 7/2.5/0.5/0.5 (dichloromethane/ethyl acetate/methanol/aqueous ammonia). 0.236 g of 4-[5-(4-isobutyl piperazin-1-yl)pyridin-2-yl]-3,4-dihydro-2H-quinoxaline-1-carboxylic acid (5-carbamoyladamantan-2-yl)amide is obtained, subsequently triturated from diethyl ether. The crystals obtained are filtered off and dried.

Provenance & Evidence