反应详情

温度

0 °C

To a round bottom flask is added 2-(2-amino-6-chloro-5-formyl-pyrimidin-4-ylamino)-N-(3-trifluoromethyl-phenyl)-acetamide (80.0 mg, 0.21 mmol, 1.0 eq.), THF (5.0 mL), and DIEA (0.036 mL, 0.21 mmol, 1.0 eq.). The flask was then cooled to 0° C. before adding sodium thiomethoxide (16.0 mg, 0.23 mmol, 1.1 eq.). The reaction was warmed to RT and stirred for 3 hrs before quenching with H2O (10 mL) and EtOAc (50 mL). The EtOAc layer washed with brine, dried with Na2SO4, and concentrated to give pure 2-(2-amino-5-formyl-6-methylsulfanyl-pyrimidin-4-ylamino)-N-(3-trifluoromethyl-phenyl)-acetamide as a yellow solid (75.0 mg, 92%). LC/MSD (HP Series 1100 MSD): Expected MW: 385, Observed M+H, 386.1, Retention time: 1.58 min. ANALYTICAL HPLC: >95%, Retention time: 4.30 min (8 minute run). 1H-NMR (d6-DMSO): 10.48 (s, 1H), 9.98 (s, 1H), 9.35 (t, 1H), 8.10 (s, 1H), 7.80 (d, 1H), 7.59 (t, 1H), 7.41 (m, 2H), 7.25 (br s, 1H), 4.25 (d, 2H), (3 thiomethyl protons are buried under DMSO peak) ppm. 1H-NMR (d-MeOH): 10.0 (s, 1H), 8.00 (s, 1H), 7.78 (d, 1H), 7.50 (t, 1H), 7.39 (d, 1H), 4.33 (s, 2H), 2.51 (s, 3H) ppm.

1. temperatureThe reaction was warmed to RT
2. custombefore quenching with H2O (10 mL) and EtOAc (50 mL)
3. washThe EtOAc layer washed with brine
4. dry with materialdried with Na2SO4
5. concentrationconcentrated