4-Chloro-6-methyl-1,3,5-triazin-2-amine → HCID 49785754, compound

Participants

Reaction Conditions

Reaction Steps

1,4-Dioxane (4.00 mL, 46762 μmol) was added to a mixture of 3-(3-chloro-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-ylamino)phenol (390 mg, 983 μmol), bis(pinacolato)diboron (299 mg, 1179 μmol), X-Phos (46.8 mg, 98.3 μmol), tris(dibenzylideneacteone)dipalladium(0) (45.0 mg, 49.1 μmol) and potassium acetate (0.154 ml, 2457 μmol) and the mixture was stirred at 100° C. for 3 h. After cooling to room temperature, 4-chloro-6-methyl-1,3,5-triazin-2-amine (213 mg, 1474 μmol) and bis(di-tert-butyl (4-dimethylaminophenyl)phosphine)dichloropalladium(II) (Aldrich, St. Louis, Mo.) (61.1 mg, 98.3 μmol) was added and the mixture was resealed and continued heating at 100° C. overnight. The mixture was allowed to cool to room temperature, filtered through a short path of Celite® (diatomaceous earth), and the filter cake was washed with EtOAc (2×20 mL). The combined organic phases were concentrated with SiO2 and purified by flash column chromatography (ISCO CombiFlash® system, Teledyne ISCO, Lincoln, Nebr.), pure DCM to 10% 2 M NH3/MeOH in DCM) to give 3-(3-(4-Amino-6-methyl-1,3,5-triazin-2-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-ylamino)phenol (7 mg, 1.5%) as a yellow solid. LCMS (API-ES) m/z 471 (M+H)+; 1H NMR (400 MHz, d6-DMSO) δ 11.98 (br. s., 1H) 9.27 (d, J=4.89 Hz, 1H) 8.59-8.78 (m, 1H) 8.26 (d, J=2.93 Hz, 1H) 7.61-7.92 (m, 1H) 7.50 (d, J=1.76 Hz, 1H) 6.81-7.26 (m, 2H) 6.24-6.50 (m, 1H) 3.49 (br. s., 2H) 3.11 (br. s., 4H) 2.87 (d, J=5.87 Hz, 3H) 2.37-2.48 (m, 7H).

Provenance & Evidence