Diisopropylethylamine → HCID 178462813, compound

Participants

Reaction Steps

To a solution of 4.3 g (0.02 mol) (2,6-dichlorophenyl)-propargylic acid (M. S. Reich et al., Bull. Soc. Chim. Fr. 21, 217-225 (1917)) in 120 ml DMF and 120 ml acetonitrile are added at RT 4.23 ml (0.025 mol) N,N-di-isopropyl-N-ethylamine, followed by a solution of 5.94 g (0.02 mol) TPTU (O-(1,2-dihydro-2-oxo-1-pyridyl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate, Fluka, Buchs, Switzerland) in 100 ml DMF. The resulting solution is stirred at RT for 5 minutes and then added dropwise to a solution of 7.36 g (0.02 mol) 4-[6-(3-amino-phenylamino)-9-ethyl-9H-purin-2-ylamino]-cyclohexanol (example 77, stage 1.2) in a 1:1 mixture of DMF and acetonitrile (240 ml). The addition takes 1.25 hrs and stirring at RT is continued for an additional hour. A second portion of preactivated (2,6-dichlorophenyl)-propargylic acid [prepared by adding 2.0 g (0.0066 mol) TPTU in 30 ml DMF to a solution of 1.3 g (0.0066 mol) (2,6-dichlorophenyl)-propargylic acid in 30 ml DMF and 30 ml acetonitrile and stirring for 5 minutes at RT] was then added dropwise over 30 minutes. After stirring for another 1.5 hrs the solvent is evaporated under reduced pressure and the residue taken up in a mixture of ethyl acetate and 10% aqueous citric acid. The aqueous phase is extracted with ethyl acetate and the combined organic layers are washed with water, saturated sodium bicarbonate solution and brine. After drying (anhydrous sodium sulfate) the ethyl acetate solution is concentrated until the product crystallises. It is collected by filtration, re-suspended in a small amount of ethyl acetate, filtered and vacuum dried. N-{3-[9-Ethyl-2-(trans-4-hydroxy-cyclo-hexylamino)-9H-purin-6-yl-amino]-phenyl}-3-(2,6-dichlorophenyl)-propargylic acid amide (7.0 g, 60%), is obtained as a colourless solid.

Provenance & Evidence