反应详情

A suspension of 4-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one (127 mg, 0.424 mmol, prepared according to procedures described in Example 230 Step C substituting 2-chloro-5-ethylpyrimidine (Aldrich) for 2-chloro-5-cyclopropylpyrimidine), sodium hydride (60 wt % mineral oil, 21 mg, 0.51 mmol) and DMF (5 mL) was purged with Argon and then stirred at room temperature for 1 h. To the reaction was added 1,2-difluoro-4-(methylsulfonyl)benzene (90 mg, 0.47 mmol, Matrix Scientific) and then heated at 110° C. for 1 h. The resulting mixture was quenched with H2O and extracted with EtOAc. The organic layer was concentrated in vacuo to a yellow solid. The solid was purified by flash chromatography (SiO2, 0 to 100% EtOAc in CH2Cl2) to yield 91 mg of the desired product as an off-white solid. 1H NMR (400 MHz, CDCl3) δ ppm 8.20 (s, 2 H), 7.83-7.91 (m, 2 H), 7.64 (dd, J=8.53, 6.78 Hz, 1 H), 7.13 (dd, J=7.53, 1.00 Hz, 1 H), 6.08 (dd, J=7.65, 2.64 Hz, 1H), 6.03 (d, J=2.51 Hz, 1 H), 4.54-4.63 (m, 1 H), 4.16-4.27 (m, 2 H), 3.60-3.70 (m, 2 H), 3.12 (s, 3H), 2.49 (q, J=7.53 Hz, 2 H),1.97-2.15 (m, 2 H),1.78-1.97 (m, 2H),1.21 (t, J=7.53 Hz, 3 H). MS (ESI) 473 (M+H).

1. customwas purged with Argon
2. temperatureheated at 110° C. for 1 h
3. customThe resulting mixture was quenched with H2O
4. extractionextracted with EtOAc
5. concentrationThe organic layer was concentrated in vacuo to a yellow solid
6. customThe solid was purified by flash chromatography (SiO2, 0 to 100% EtOAc in CH2Cl2)