Sodium Hydroxide → 4-(1-((9-methyl-6-morpholino-2-(1H-pyrrolo[2,3-c]pyridin-4-yl)-9H-purin-8-yl)methyl)piperidin-4-yl)morpholine

Participants

Reaction Conditions

Reaction Steps

To a degassed mixture of 4-(1-((9-methyl-6-morpholino-2-(tributylstannyl)-9H-purin-8-yl)methyl)piperidin-4-yl)morpholine (859 mg, 1.24 mmol), 4-bromo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-c]pyridine (385 mg, 1.14 mmol), copper(I) iodide (326 mg, 1.71 mmol) in 1,4-dioxane (10 mL) was added Pd(PPh3)4 (100 mg, 0.09 mmol). The reaction mixture was stirred at 110° C. for 18 hours. The reaction mixture was concentrated and then dissolved in DCM and filtered through a column of silica gel (20% MeOH in DCM). The elutant was concentrated to give a yellow paste which was taken up in ethanol (2 mL) and 1,4-dioxane (3 mL). A 12 M aqueous NaOH solution (0.5 mL) was then added and the resulting mixture was stirred at room temperature for 1 hour. The reaction mixture was then concentrated and the crude product was purified by flash chromatography using a Biotage KP—NH column (10% MeOH in DCM) followed by RP-HPLC to give 124. LCMS: M+H+=518.3. 1H-NMR (400 MHz, DMSO-d6): δ 11.70 (s, 1H), 9.14 (s, 1H), 8.79 (s, 1H), 7.70 (m, 1H), 7.43 (m, 1H), 4.30 (s, br, 4H), 3.88 (s, 3H), 3.78 (m, 4H), 3.70 (s, 2H), 3.54 (m, 4H), 2.86 (m, 2H), 2.43 (m, 4H), 2.09 (m, 2H), 1.75 (m, 2H), 1.36 (m, 3H).

Provenance & Evidence