反应详情

温度

160 °C

As shown in FIG. 4—step v, to a solution of compound 1019 (31.7 mg, 0.100 mmol) in DME (0.50 mL) was added a nucleophilic amine (pyrrolidine, 10 μL, 0.11 mmol) and diisopropylethylamine (25.8 mg, 34.8 μL, 0.200 mmol). The mixture was heated at 160° C. with microwave for 5 min, followed by the addition of 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-7H-pyrrolo[2,3-d]pyrimidine (compound 1005, 39.9 mg, 0.100 mmol) and a solution of CsF (30 mg, 0.20 mmol) in water (0.25 mL). The mixture was heated at 160° C. with microwave for 5 min. The reaction mixture was filtered through a short pad of silica gel using EtOAc/hexanes as eluent to provide, after concentration in vacuo, the crude intermediate tosylate. This intermediate was dissolved in 1 mL of dry methanol and 200 uL of 25% sodium methoxide in methanol was added. The reaction mixture was stirred at 60° C. for 1 hour and quenched with trifluoroacetic acid. Purification by reversed-phase HPLC gave 35.0 mg of 2-[4-pyrrolidin-1-yl-6-(7H-pyrrolo[2,3-d]pyrimidin-5-yl)-pyrimidin-2-ylamino]-N-(2,2,2-trifluoro-ethyl)-propionamide TFA salt (a compound of formula IX where R10 is 1-pyrrolidine).

1. temperatureThe mixture was heated at 160° C. with microwave for 5 min
2. filtrationThe reaction mixture was filtered through a short pad of silica gel
3. customto provide
4. concentrationafter concentration in vacuo
5. dissolutionThis intermediate was dissolved in 1 mL of dry methanol
6. addition200 uL of 25% sodium methoxide in methanol was added
7. customquenched with trifluoroacetic acid
8. customPurification by reversed-phase HPLC