反应详情

Phenyl chloroformate (0.03 mL, 0.24 mmol) was added slowly to a solution of 3-Cyclopropyl-1′-methyl-1′H-[1,4′]bipyrazolyl-5-ylamine (Preparation 297, 40 mg, 0.19 mmol) and pyridine (0.03 mL) in THF (2 mL) at 00° C. and the mixture was stirred at room temperature for 4 hours. A solution of (5-Amino-pyridin-3-yl)-(7-isopropyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-methanone (Preparation 95) (55.4 mg, 0.19 mmol) in DMF (1 mL) and was then added and the reaction mixture heated at 100° C. for 16 hours. The mixture was cooled and diluted with ethyl acetate (15 mL), and washed with aqueous saturated NaHCO3 solution (2×10 mL), water (10 mL), brine (10 mL), dried over sodium sulphate and evaporated to dryness in vacuo. The crude material was purified over preparative TLC plate (eluting with 5% methanol in DCM) to afford the title compound as off white solid in 15% yield, 15 mg. 1H NMR (400 MHz, DMSO-d6) δ: 0.64-0.65 (m, 2H), 0.85-0.88 (m, 2H), 1.56 (d, 6H), 1.82-1.85 (m, 1H), 3.89 (s, 3H), 5.09-5.12 (m, 1H), 6.10 (s, 1H), 7.66 (s, 1H), 8.05 (s, 1H), 8.36 (s, 1H), 8.52 (s, 1H), 8.61 (br s, 1H), 8.65 (s, 1H), 8.78 (s, 1H), 8.99 (s, 1H), 9.45 (s, 2H); LCMS (system 10): Rt=2.75 min; m/z 511 [M+H]+.

1. temperaturethe reaction mixture heated at 100° C. for 16 hours
2. temperatureThe mixture was cooled
3. washwashed with aqueous saturated NaHCO3 solution (2×10 mL), water (10 mL), brine (10 mL)
4. dry with materialdried over sodium sulphate
5. customevaporated to dryness in vacuo
6. customThe crude material was purified over preparative TLC plate (eluting with 5% methanol in DCM)