Methanol → [4-(5-Diethylaminomethyl-2,4-dimethyl-1H-pyrrol-3-yl)-pyrimidin-2-yl]-(4-fluoro-phenyl)-amine

Participants

Reaction Steps

Diethylamine (40 μL, 0.31 mmol) was diluted with methanol (0.5 mL) and formaldehyde (30 μL of a 37% w/w aq solution, 0.37 mmol) was added. [4-(2,4-Dimethyl-1H-pyrrol-3-yl)-pyrimidin-2-yl]-(4-fluoro-phenyl)-amine (87 mg, 0.31 mmol) was added in small portions and the mixture was heated to reflux. After 1.5 h the mixture was diluted with H2O (10 mL). The resulting precipitate was filtered and triturated in 2 M aq HCl. The mixture was filtered and the filtrate was washed with 2 M aq NaOH. The filtrate was extracted with EtOAc (3×15 mL). The combined organic extracts were washed (brine), dried (MgSO4), filtered, and evaporated in vacuo. The crude product was purified by SiO2 chromatography (heptane/EtOAc gradient elution) to afford the title compound (36 mg) as an orange solid after recrystallisation from iPr2O. M.p. 71.9–74.2° C. MS: [M+H]+=367.7 (C21H26FN5 requires 367.5). 1H-NMR (CD3OD) δ: 1.10 (t, 6H, J=7.1 Hz, CH3), 2.19 (s, 3H, CH3), 2.41 (s, 3H, CH3), 2.58 (t, 4H, J=7.8 Hz, CH2), 3.56 (s, 2H, CH2), 6.78 (d, 1H, J=5.6 Hz, pyrimidinyl-H), 7.00 (t, 2H, J=8.5 Hz, Ph-H), 7.61–7.63 (m, 2H, Ph-H), 8.22 (d, 1H, J=5.4 Hz, pyrimidinyl-H).

Provenance & Evidence