1. In a dry reaction flask, morpholine (871 mg, 10 mmol) and N,N-diisopropylethylamine (2.6 g, 20 mmol) were sequentially added to a solution of n-butanol (100 mL) containing 3-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-5-yl)benzonitrile (2.5 g, 9.8 mmol).
2. The reaction mixture was heated to reflux with continuous stirring for 3 hours.
3. Upon completion of the reaction, the solvent was removed by rotary evaporator under reduced pressure.
4. The residue was purified by silica gel column chromatography with the eluent being a solvent mixture of ethyl acetate and petroleum ether (1:1, v/v).
5. After collection of the target fraction, the target fraction was further recrystallized using ethyl acetate and tert-butyl methyl ether to give the white solid product 3-(4-morpholino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)benzonitrile.
6. Yield: 770 mg, 2.52 mmol, 26%. 7.
7. Product characterization: LCMS m/z 306.0 [M + H]+. 1H NMR (400 MHz, DMSO-d6) δ 12.34 (br s, 1H), 8.41 (s, 1H), 7.99-8.02 (m, 1H), 7.89 (br d, J = 8 Hz, 1H), 7.76 (br d, J = 7.5 Hz, 1H), 7.71 (s, 1H), 7.81 (s, 1H), 7.82 (br d, J = 7.5 Hz, 1H). 7.71 (s, 1H), 7.68 (dd, J = 7.8, 7.8 Hz, 1H), 3.44-3.50 (m, 4H), 3.11-3.17 (m, 4H).