Hydrochloric Acid → HCID 178492177, 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 aniline (0.161 mL, 1.770 mmol) (Fluka, Buchs, Switzerland) 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 (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 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). This gave N2-(6-methoxypyridin-3-yl)-3-(2-methyl-9H-purin-6-yl)-N5-phenylpyridine-2,5-diamine (0.180 g, 0.424 mmol, 96% yield) as a tan solid. MS (ESI pos. ion) m/z 425 (M+H)+. 1H NMR (400 MHz, CD3OD) δ 9.85 (s, 1H); 8.52 (s, 1H); 8.41 (s, 1H); 7.87 (s, 1H); 7.52 (d, J=7.43 Hz, 2H); 7.39 (d, J=7.43 Hz, 1H); 7.21-7.29 (m, 2H); 7.10 (s, 2H); 7.00 (d, 1H); 6.88 (s, 1H); 3.98 (s, 3H); 2.83 (s, 3H).

Provenance & Evidence