Diisopropylethylamine → (S)-1-ethyl-3-(4-(6-(3-ethylmorpholino)-7-methyl-7H-purin-2-yl)phenyl)urea

Participants

Reaction Steps

Preparation of (S)-4-(2-chloro-7-methyl-7H-purin-6-yl)-3-ethylmorpholine (e-1) was prepared as described in Example 2 with the modification that (S)-3-ethylmorpholine HCl salt was used in place of morpholine and the 3.5/1 mixture of ethanol/DMF required gentle heating was necessary to effect dissolution of (a-2). Once solubilized, the reaction mixture remained homogeneous upon cooling to room temperature. Diisopropylethylamine and (S)-3-ethylmorpholine HCl were added at room temperature and the reaction stirred for 20 h. Additional heating to 60° C. for 24 h was required for complete conversion to (e-1). The intermediate compound (e-1) was obtained as a tan solid in 87% yield after workup and was taken directly into the next step. 1H NMR (400 MHz, DMSO d6) 8.43 (s, 1H), 4.03 (m, 1H), 3.94 (s, 3H), 3.78 (m, 3H), 3.62 (m, 1H), 3.52 (dd, J=7.3, 18.4 Hz, 2H), 1.79 (m, 2H), 0.79 (t, J=7.4 Hz, 3H). LC/MS-m/z+282.5 (M+H)+.

Provenance & Evidence