Sodium Carbonate → tert-butyl(3S)-3-[4-(2-aminopyrimidin-5-yl)-2-(methylsulfanyl)-5,6-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-3-methylpyrrolidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a suspension of tert-butyl(3S)-3-[4-chloro-2-(methylsulfanyl)-5,6-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-3-methylpyrrolidine-1-carboxylate (1.24 g, 3.22 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine (1.0 g, 4.6 mmol) in dioxane (16 mL) was added 1 M Na2CO3 solution (13 mL, 12.9 mmol) at room temperature. The reaction mixture was purged with nitrogen for a few minutes before adding PdCl2(dppf)-DCM (395 mg, 0.484 mmol). The reaction mixture was heated at 120° C. for 40 h in a microwave reactor. The mixture was filtered through a pad of Celite® rinsing with EtOAc several times, concentrated and purified via ISCO normal phase silica gel chromatography (40 g column) with a 0-100% gradient of EtOAc/Heptane to give the title compound (828 mg, 58%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.72 (d, J=4.6 Hz, 2 H), 7.06 (s, 2 H), 3.79-3.64 (m, 3 H), 3.63-3.51 (m, 1 H), 3.39-3.34 (m, 2 H), 3.21-3.14 (m, 2 H), 2.45 (s, 3 H), 2.41-2.27 (m, 1 H), 2.10-1.99 (m, 1 H), 1.40 (s, 9 H), 1.28 (s, 3 H). m/z (APCI+) for C21H29N7O2S 444.2 (M+H)+.

Provenance & Evidence