Diisopropylethylamine → HCID 44540063, compound

Participants

Reaction Steps

A mixture of 1-(1-methylethyl)-1H-imidazole-2-carboxylic acid (467 mg, contained 50% ethyl 1H-imidazole-2-carboxylate plus inorganic impurities) (now available pure from AKos), HATU (576 mg), and DIPEA (0.793 ml) in DMF (2 ml) was stirred at RT for 10 min. 6-(1H-Indol-4-yl)-1H-indazol-4-amine (188 mg) in DMF (3 ml) was then added and the mixture was stirred at RT. After 3 h at RT, a further quantity of premixed [1-(1-methylethyl)-1H-imidazole-2-carboxylic acid (467 mg), HATU (576 mg), and DIPEA (0.793 ml) in DMF (2 ml)] was added to the reaction mixture and stirring was continued for 2 h at RT. Water (0.5 ml) was added to the reaction mixture, and it was then evaporated to dryness. The residue was partitioned between ethyl acetate (25 ml) and water (10 ml). The phases were separated and the aqueous phase was extracted with further ethyl acetate (2×25 ml). The combined organic extracts were dried over anhydrous sodium sulphate and evaporated to give a brown oily residue which was dissolved in DCM (15 ml) and applied to a 100 g silica SPE cartridge. The cartridge was eluted on a Flashmaster (II) using a gradient of 0-100% ethyl acetate in cyclohexane over 60 min to give a pale brown oil which was dissolved in DCM (5 ml) and applied to a 20 g silica SPE cartridge. The cartridge was eluted with a gradient of 0-100% ethyl acetate in cyclohexane over 40 min followed by 0-20% methanol in ethyl acetate over 15 min to give the title compound (53 mg) as a buff-coloured solid.

Provenance & Evidence