N-(3-Aminopropyl)morpholine → N2-(3-chlorophenyl)-N4-(3-morpholin-4-yl-propyl)-pyrimidine-2,4-diamine

Beteiligte Stoffe

Reaktionsschritte

To 4-chloro-N-(3-chlorophenyl)pyrimidin-2-amine, 3, (0.2 g, 0.84 mmol) in THF (4 mL) is added diisopropylethylamine (0.29 mL, 1.67 mmol) followed by 3-morpholino-propylamine (0.245 mL, 1.67 mmol). The resulting mixture was heated to reflux for 6 hours. Another 2 equivalents of 3-morpholinopropylamine (0.245 mL, 1.67 mmol) is added and the reaction heated to reflux and stirred for 18 hours. The resulting mixture is heated to reflux for 18 hours. The reaction is cooled to room temperature and concentrated in vacuo. The residue is diluted with 5 mL water and extracted with EtOAc (3×25 mL). The combined organic layers are dried (MgSO4) and concentrated in vacuo. The residue is diluted with 5 mL water and extracted with EtOAc (3×25 mL). The combined organic layers are dried (MgSO4) and concentrated in vacuo. This residue is purified over silica (6% MeOH in CH2Cl2 with 0.7% Et3N) to afford 0.120 g (41% yield) of the desired compound. 1H NMR (DMSO-d6, 300 MHz): δ 1.68-1.75 (m, 2H), 2.34-2.40 (m, 6H), 3.30-3.35 (m, 2H), 3.55-3.58 (m, 4H), 5.97 (d, J=5.7 Hz, 1H), 6.88 (d, J=7.2 Hz, 1H), 7.19-7.28 (m, 2H), 7.59 (d, J=7.2 Hz, 1H), 7.80 (br s, 1H), 8.13 (br s, 1H), 9.19 (br s, 1H). MS (ESI, pos. ion) m/z: 348 (M+1).

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