1-Amino-2-propanol → 4-(4'-Ethyl-2'-(2-hydroxy-2-methylpropylamino)-4,5'-bipyrimidin-2-ylamino)benzonitrile

Participants

Reaction Steps

4-(4′-Ethyl-2′-(methylthio)-4,5′-bipyrimidin-2-ylamino)benzonitrile (36a) (48.6 mg, 0.112 mmol) and 1-amino-2-propanol (29.8 mg, 0.335 mmol) were dissolved in THF (540 μl) and NMP (54.0 μl), then the reaction mixture was microwaved at 150° C. for 1 hour. Additional 1-amino-2-methylpropanol (99.8 mg, 1.12 mmol) was added, and the reaction mixture was microwaved further at 150° C. an additional 1 hour. Additional 1-amino-2-methylpropanol (99.8 mg, 1.12 mmol) was added, and the reaction mixture was microwaved further at 200° C. The crude reaction mixture was purified by reverse-phase HPLC [30-100% organic phase over 15 minutes using 0.1% TFA modifier] followed by Biotage™ silica gel chromatography [10 g SNAP column, 100% DCM to 10% MeOH/DCM] to obtain the desired product as a pale yellow solid (4.14 mg, 9% yield). 1H NMR (400 MHz, MeOD) δ ppm 1.20-1.27 (m, 9 H) 2.94 (q, J=7.58 Hz, 2 H) 3.51 (s, 2 H) 4.55 (s, 1 H) 7.04 (d, J=5.56 Hz, 1 H) 7.62 (m, J=9.09 Hz, 2 H) 7.96 (m, J=8.59 Hz, 2 H) 8.44 (s, 1 H) 8.52 (d, J=5.05 Hz, 1 H). HRMS (ES+) for C21H23N7O.H+ [MH+]: calcd, 390.2042. found, 390.2023. UV-LC: 96.40/95.08% UV purity at 214/254 nm; tR=5.31 minutes over 7.75 minutes.

Provenance & Evidence