Hydrochloric Acid → HCID 178490967, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 5-chloro-N-(6-methoxypyridin-3-yl)-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-amine (0.230 g, 0.509 mmol) and 3-methoxyaniline (0.142 mL, 1.272 mmol) (Aldrich, St. Louis, Mo.) in THF (10 mL) was treated with sodium tert-butoxide (0.147 g, 1.527 mmol) and 2-di-t-butylphosphino-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (0.040 g). The mixture was deoxygenated and treated with Pd2(dba)3 (0.030 g, 0.033 mmol) under N2. The flask was fitted with a reflux condenser, then placed into a pre-heated bath at 80° C. and stirred overnight. The reaction mixture was diluted with saturated aqueous NaHCO3 (15 mL) and extracted with CH2Cl2 (2×25 mL). The combined organic extracts were washed with NaHCO3 (20 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give a tan oil. A glass microwave reaction vessel was charged with the crude oil and 1 N aqueous HCl (1.5 mL) in THF (2.5 mL). The reaction mixture was stirred and heated in a Discover model microwave reactor (CEM, Matthews, N.C.) at 100° C. for 8 min (100 watts, Powermax feature on). The mixture was diluted with MeOH, concentrated and triturated with THF. The precipitate was collected by filtration and washed with diethyl ether (3×25 ml). The solid (0.178 g) was neutralized with SiliCycle Si-Carbonate Silica Gel (SiliCycle Inc., Quebec City, Canada) (1.8 g) in a mixture of THF/DCM (1:1; 10 mL) and allowed to stir under inert atmosphere overnight. The mixture was filtered with a fine-fritted funnel. The desired material which was still attached to the Silica-polymer, was released by washing the silica with methanol (2×10 mL) and concentrated. The residue was triturated with diethyl ether and the precipitate was collected by filtration to give N5-(3-methoxyphenyl)-N2-(6-methoxypyridin-3-yl)-3-(2-methyl-9H-purin-6-yl)pyridine-2,5-diamine (0.040 g, 0.088 mmol, 17.29% yield) as a tan solid. MS (ESI pos. ion) m/z 456 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 12.50 (s, 1H); 9.75 (s, 1H); 8.54 (s, 2H); 8.17 (s, 2H); 8.08 (s, 1H); 7.08 (s, 1H); 6.83 (d, J=8.80 Hz, 1H); 6.51-6.59 (m, 2H); 6.32 (s, 1H); 3.84 (s, 3H); 3.71 (s, 3H); 2.86 (s, 3H).

Provenance & Evidence