1-Amino-5-bromoisoquinoline → 2-(1-((2-(1-aminoisoquinolin-5-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)piperidin-4-yl)propan-2-ol

Participants

Reaction Conditions

Reaction Steps

To a degassed mixture of 2-(1-((9-methyl-6-morpholino-2-(tributylstannyl)-9H-purin-8-yl)methyl)piperidin-4-yl)propan-2-ol (256 mg, 0.386 mmol), 5-bromoisoquinolin-1-amine (86 mg, 0.386 mmol), copper(I) thiophene-2-carboxylate (74 mg, 0.386 mmol) in 1,4-dioxane (4 mL) was added Pd(PPh3)4 (45 mg, 0.039 mmol). The reaction mixture was heated in the microwave at 140° C. for 35 minutes. The reaction mixture was then loaded onto a Biotage Isolute SPE SCX-2 column The column was first washed with MeOH. The product was eluted with 2 M NH3 in MeOH and concentrated. The crude was further purified by RP-HPLC to give 147 (36.3 mg, 18.2%). LCMS: M+H+=517.3. 1H-NMR (400 MHz, DMSO-d6): δ 8.28 (d, 1H), 8.11 (d, 1H), 7.79 (d, 1H), 7.70 (d, 1H), 7.53 (t, 1H), 6.80 (s, 2H), 4.23 (s, br, 4H), 4.09 (s, 1H), 3.81 (s, 3H), 3.73 (m, 6H), 2.90 (m, 2H), 2.02 (m, 2H), 1.66 (m, 2H), 1.19 (m, 3H), 1.02 (s, 6H)

Provenance & Evidence