Tetrahydrofuran → 4-(2'-(2-Hydroxy-2-methylpropylamino)-4'-isopropyl-4,5'-bipyrimidin-2-ylamino)benzonitrile

Participants

Reaction Steps

4-(4′-Isopropyl-2′-(methylthio)-4,5′-bipyrimidin-2-ylamino)benzonitrile (36b) (51.1 mg, 0.141 mmol) and 1-amino-2-methylpropanol (126 mg, 1.410 mmol) were dissolved in THF (513 μl) and NMP (51.3 μl), then the reaction mixture was microwaved at 200° C. for 2 hours. The reaction was approximately 10% complete. Additional 1-amino-2-methylpropanol (126 mg, 1.410 mmol) was added, and the reaction mixture was microwaved at 200° C. for an additional 2 hours. The reaction mixture was microwaved at 200° C. for additional 3.5 hours. The crude reaction mixture was purified by reverse-phase HPLC [30-100% organic phase over 15 minutes using 0.1% TFA modified mobile phase] to obtain the desired product as a yellow foamy solid. 1H NMR (400 MHz, MeOD) δ ppm 1.27 (d, J=6.57 Hz, 6H) 1.30 (s, 6H) 3.43-3.65 (m, 2H) 3.71 (ddd, J=13.52, 6.69, 6.57 Hz, 1H) 7.08 (d, J=5.05 Hz, 1H) 7.63 (m, J=9.09 Hz, 2H) 7.95 (m, J=8.59 Hz, 2H) 8.45 (s, 1H) 8.61 (d, J=5.05 Hz, 1H). HRMS (ES+) for C22H25N7O.H+ [MH+]: calcd, 404.2199; found, 404.2201. UV-LC: 95.41/100% UV purity at 214/254 nm; tR=5.73 minutes over 7.75 minutes.

Provenance & Evidence