Potassium Carbonate → Benzothiazol-6-yl-[6-(1,2,3,6-tetrahydropyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine trihydrochloride

Participants

Reaction Conditions

Reaction Steps

To a suspension of benzothiazol-6-yl-(6-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine (4.05 g, 10.3 mmol) in 1,2-dimethoxyethane (125 mL) and water (25 mL) were added 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (3.50 g, 11.3 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloro palladium(II), complex with dichloromethane (1:1) (420 mg, 0.51 mmol) and potassium carbonate (2.85 g, 20.6 mmol). The flask was evacuated and refilled with N2 (3×). The mixture was heated at 80° C. overnight. The reaction mixture was diluted with EtOAc (200 mL) and water (50 mL) and filtered through a pad of celite. The organic phase was separated, and the aqueous phase was extracted with EtOAc (2×50 mL). The combined organic phases were washed with brine (100 mL), and dried over anhydrous sodium sulfate. Evaporation under reduced pressure afforded a brown solid. To a suspension of this crude material in methylene chloride (30 mL) was added 4M HCl/1,4-dioxane (30 mL), and the resulting mixture was stirred at rt overnight. The mixture was diluted with CH2Cl2 (30 mL), and the light-yellow solid was collected by filtration and dried in vacuo to give the title compound. LC-MS (ES, Pos.): 349 [MH+]. 1H NMR (DMSO-d6, 400 MHz): δ=2.51 (m, 2H), 3.34 (m, 2H), 3.81 (m, 2H), 6.52 (s, 1H), 7.09 (s, 1H), 7.73 (dd, J=8.7 Hz, 2.0 Hz, 1H), 8.22 (d, J=8.7 Hz, 1H), 8.36 (d, J=2.0 Hz, 1H), 8.51 (s, 1H), 9.46 (s, 1H).

Provenance & Evidence