Sodium Carbonate → 5-[7-(3,3-difluorocyclobutyl)-2-(methylsulfanyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl]pyrimidin-2-amine

Participants

Reaction Conditions

Reaction Steps

To a suspension of 4-chloro-7-(3,3-difluorocyclobutyl)-2-(methylsulfanyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine (844 mg, 2.89 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine (920 mg, 4.20 mmol) in 1,4-dioxane (24 mL), was added 1 M aqueous solution of Na2CO3 (9 mL, 8.68 mmol) at room temperature. The reaction was purged with nitrogen for a few minutes before adding PdCl2(dppf)-DCM (354 mg, 0.434 mmol). The reaction was heated at 120° C. for 1 h in a microwave reactor. The mixture was cooled to room temperature and filtered through Celite® rinsing with EtOAc. The filtrate was concentrated and DCM was added, resulting in precipitation that was filtered to give a crude title compound (768 mg, ˜80% purity). The mother liquor was purified via silica gel chromatography using a gradient of EtOAc/heptane to afford an additional 250 mg of the title compound as a white solid (95% purity). 1H NMR (400 MHz, DMSO-d6) δ 8.76 (s, 2 H), 7.08 (s, 2 H), 4.51-4.36 (m, 1 H), 3.71 (t, J=8.2 Hz, 2 H), 3.22 (t, J=8.2 Hz, 2 H), 3.13-2.94 (m, 2 H), 2.94-2.80 (m, 2 H), 2.47 (s, 3 H). m/z (APCI+) for C15H16F2N6S 351.1 (M+H)+.

Provenance & Evidence