N,N'-Dimethylethylenediamine → ethyl 4-[1-cyclopropyl-6-(pyridin-2-ylmethoxy)-1H-pyrrolo[2,3-b]pyridin-3-yl]-3-oxopiperazine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of 3-bromo-1-cyclopropyl-6-(pyridin-2-ylmethoxy)-1H-pyrrolo[2,3-b]pyridine (0.263 g, 765 μmol), ethyl 3-oxopiperazine-1-carboxylate (0.158 g, 0.918 mmol), N,N′-dimethylethane-1,2-diamine (33.8 μL, 0.313 mmol), copper(I) iodide (32 mg, 168 μmol), potassium phosphate (tribasic, n-hydrate) (0.179 g, 841 μmol) in DMF (10 mL) is heated at 120° C. for 15 h. The mixture is cooled to room temperature and further copper(I) iodide (0.145 g, 765 μmol), potassium phosphate (tribasic, n-hydrate) (0.536 g, 2.52 mmol) and N,N′-dimethylethane-1,2-diamine (165 μL, 1.53 mmol) are added, followed by ethyl 3-oxopiperazine-1-carboxylate (0.132 g, 0.765 mmol). After further heating for 24 h under nitrogen at 100° C., the mixture is concentrated in vacuo, diluted with MeOH and poured onto a SCX-2 ion-exchange column. This is washed with 3 column volumes of MeOH and then the product collected in the subsequent one column volume flush of 7 M methanolic ammonia. The solution is concentrated in vacuo and purified by column chromatography on silica, eluting with 0 to 100% EtOAc in isohexane, to give the title compound as a yellow oil (40 mg, 0.09 mmol). MS (m/z): 436 (M+1). 1H-NMR (400 MHz, CDCl3): 0.89-0.99 (m, 4H), 1.31 (t, 3H), 3.31-3.37 (m, 1H), 3.76-3.78 (m, 2H), 3.82-3.88 (m, 2H), 4.22 (q, 2H), 4.33 (s, 2H), 5.60 (s, 2H), 6.72 (d, 1H), 7.00 (s, 1H), 7.18-7.22 (m, 1H), 7.48-7.52 (m, 1H), 7.64-7.69 (m, 2H), 8.59-8.61 (m, 1H).

Provenance & Evidence