Hydrochloric Acid → HCID 178495869, 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 (0.150 g, 0.332 mmol) and 2-methoxyethylamine (0.114 mL, 1.328 mmol) (Aldrich, St. Louis, Mo.) in THF (10 mL) was treated with sodium tert-butoxide (0.096 g, 0.996 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 (0.030 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 water (10 mL) and extracted with 4:1 CHCl3/isopropanol (2×20 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 diluted with methanol and then concentrated. The mixture was triturated with acetonitrile and allowed to stir 5 minutes. The precipitate was collected by filtration and washed with diethyl ether (3×25 mL). The solid was neutralized with 1 N aqueous sodium hydroxide and extracted with chloroform/isopropanol (4:1). The organic layer was dried over sodium sulfate, filtered and concentrated. The residue was diluted with diethyl ether and the precipitate was collected by filtration, washing with diethyl ether (3×20 ml) and finally with hexanes. This gave N5-(2-methoxyethyl)-N2-(6-methoxypyridin-3-yl)-3-(2-methyl-9H-purin-6-yl)pyridine-2,5-diamine (0.035 g, 0.086 mmol, 25.9% yield) as a tan solid. MS (ESI pos. ion) m/z 407 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 12.06 (s, 1H); 9.20 (s, 1H); 8.60 (s, 1H); 8.47 (s, 1H); 8.12 (d, 1H); 7.90 (d, J=2.35 Hz, 1H); 6.82 (d, 1H); 5.42 (s, 1H); 3.82 (s, 6H); 3.58 (t, J=5.58 Hz, 2H); 3.26 (s, 3H); 2.85 (s, 3H).

Provenance & Evidence