Hydrochloric Acid → HCID 178463357, 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 (0.200 g, 0.443 mmol) and ethylamine (0.553 mL, 1.106 mmol) (Aldrich, St. Louis, Mo.) in THF (10 mL) was treated with sodium tert-butoxide (0.128 g, 1.328 mmol) and 2-di-t-butylphosphino-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (0.030 g). The mixture was deoxygenated and treated with Pd2(dba)3 (0.041 g, 0.044 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 (10 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 (3 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 concentrated and neutralized with SiliCycle Si-Carbonate Silica Gel (SiliCycle Inc., Quebec City, Canada) (0.800 g). The mixture was diluted with THF (5 mL) and allowed to stir under inert atmosphere overnight. The mixture was concentrated, diluted with DCM (10 mL) and filtered. The desired product was released from the silica by rinsing with methanol (20 mL). The filtrate was concentrated and triturated with diethyl ether to give N5-ethyl-N2-(6-methoxypyridin-3-yl)-3-(2-methyl-9H-purin-6-yl)pyridine-2,5-diamine (0.065 g, 0.173 mmol, 39.0% yield) as a tan solid. MS (ESI pos. ion) m/z 377 (M+H)+. 1H NMR (400 MHz, CD3OD) δ 8.65 (d, 1H); 8.35 (d, 1H); 8.20 (s, 1H); 7.92 (d, 1H); 7.76 (s, 1H); 6.75 (d, 1H); 3.87 (s, 3H); 3.20 (m, 2H); 2.80 (s, 3H); 1.29 (s, 3H).

Provenance & Evidence