Ammonia → 4-(2-(5-Methoxypyridin-3-ylamino)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine

Participants

Reaction Steps

A stirred solution of 2-(2-fluoro-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-4-methyl-6-(methylthio)-1,3,5-triazine (200 mg, 0.485 mmol) and 5-methoxypyridin-3-amine (Astatech, Inc., 90 mg, 0.727 mmol) in DMF (5.00 mL, 1.000 mmol) was treated with 1.0 M LiHMDS in THF (1.939 mL, 1.939 mmol) at 0° C. and the mixture was stirred for 1 h. The reaction mixture was diluted with water (10 mL each) and ethyl acetate (15 mL). The separated aqueous layer was extracted with ethyl acetate (2×10 mL) and the combined organic layers were washed with brine, dried over Na2SO4, and concentrated to give the crude residue which was heated with 2.0 M ammonia in IPA (3.00 mL, 6.00 mmol) in a sealed tube at 90° C. overnight. After cooling, the mixture was adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep pre-packed silica gel column (pure DCM to 5% MeOH in DCM) to give 4-(2-(5-methoxypyridin-3-ylamino)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (44 mg, 0.091 mmol, 18.69% yield) as a yellow solid. 1H NMR (400 MHz, d6-DMSO) δ 12.13 (s, 1H); 8.74 (s, 1H); 8.55 (s, 1H); 8.31 (s, 1H); 8.19 (br. s., 1H); 7.93 (br. s., 2H); 7.78 (br. s., 1H); 3.86 (s, 3H); 3.52 (s, 2H); 3.11 (br. s., 4H); 2.87 (s, 3H); 2.46-2.50 (m, 4H); 2.46 (s, 3H). m/z (ESI, +ve ion) 486.1 (M+H)+.

Provenance & Evidence