Benzylamine → n5-Benzyl-n2-(6-methoxypyridin-3-yl)-3-(2-methyl-9-(tetrahydro-2h-pyran-2-yl)-9h-purin-6-yl)pyridine-2,5-diamine

Participants

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 (0.160 g, 0.354 mmol) and benzylamine (0.155 mL, 1.416 mmol) (Source: Aldrich) in THF (10 mL) was treated with sodium tert-butoxide (0.102 g, 1.062 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 (0.032 g, 0.035 mmol) under N2. The flask was fitted with a reflux condenser, then placed into a pre-heated bath at 90° 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. This was adsorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 1% to 5% MeOH in CH2Cl2 over 25 minutes to give N5-benzyl-N2-(6-methoxypyridin-3-yl)-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridine-2,5-diamine as a tan solid. This material was added to a glass microwave reactor vial along with 1 N aqueous HCl (1 mL) and THF (3 mL). The mixture was stirred and heated in a Discover model microwave reactor (CEM, Matthews, N.C.) at 100° C. for 10 min (100 watts, Powermax feature on). The mixture was concentrated in-vacuo and diluted with DCM and 1 N aqueous NaOH. The mixture was extracted and the organic layer was dried over sodium sulfate, filtered and concentrated. The residue was diluted with ethyl ether and the precipitate was collected by filtration and washed with diethyl ether (5×25 mL). This gave N5-benzyl-N2-(6-methoxypyridin-3-yl)-3-(2-methyl-9H-purin-6-yl)pyridine-2,5-diamine (0.065 g, 0.148 mmol, 41.9% yield) as a tan solid. MS (ESI pos. ion) m/z 439 (M+H)+. 1H NMR (400 MHz, CD3OD) δ 8.56 (s, 1H); 8.21 (s, 1H); 8.11 (s, 1H); 7.80 (d, 1H); 7.59 (s, 1H); 7.35 (d, 2H); 7.22 (t, 2H); 7.12 (m, 1H); 6.64 (d, 1H); 4.31 (s, 2H); 3.76 (s, 3H); 2.69 (s, 3H).

Provenance & Evidence