Sodium Carbonate → HCID 118436652, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of tert-butyl(3R)-3-[4-chloro-2-(morpholin-4-yl)-5,6-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-3-methylpyrrolidine-1-carboxylate (150 mg, 0.354 mmol) in dioxane (3 mL) was added 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine (104 mg, 0.471 mmol), and 1 M aqueous Na2CO3 (1.3 mL, 51.3 mmol). Nitrogen was bubbled through the suspension for a few minutes before PdCl2(dppf)2-DCM (24 mg, 0.029 mmol) was added. The vial was crimp sealed and the reaction was heated at 120° C. for 30 min in a microwave reactor. The mixture was partitioned between EtOAc and aqueous NaHCO3. The aqueous layer was extracted with EtOAc (2x). The combined organic layers were dried over MgSO4 and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using a gradient of 0-10% (MeOH with 10% NH4OH)/(EtOAc/DCM, 1:1) to give 150 mg (88%) of the title compound as a crisp foam (˜85% pure). This material was taken into the next step without further purification. 1H NMR (400 MHz, 80° C., DMSO-d6) δ 8.72 (s, 2 H), 6.60 (br s, 2 H), 3.80-3.62 (m, 11 H), 3.54 (q, J=8.9 Hz, 1 H), 3.42-3.34 (m, 1 H), 3.33-3.23 (m, 1 H), 3.09 (t, J=8.1 Hz, 2 H), 2.44-2.34 (m, 1 H), 2.08-1.99 (m, 1 H), 1.42 (s, 9 H), 1.31 (s, 3 H).

Provenance & Evidence