反应详情

To a solution of 4-(5-bromo-pyridin-3-yl)-2-(6-methyl-pyridin-2-yl)-7H-pyrrolo[2,3-d]pyrimidine (Example 16) (1 eq, 0.81 mmol, 300 mg) in THF (5 ml), 1-methylpiperazine (Sigma-Aldrich, St. Louis, USA) (1.25 eq, 1.01 mmol, 0.114 ml), Pd2(dba)3 (0.04 eq, 0.032 mmol, 29.7 mg), and 2-(dicyclohexylphosphino)biphenyl (0.08 eq, 0.065 mmol, 25.5 mg) are added. After addition of LHMDS (1 M in THF, 2.2 eq, 1.8 mmol, 1.8 ml) the mixture is refluxed for 5 h, cooled down and quenched by addition of aqueous HCl solution (2M, 5 ml). The mixture is adjusted to pH 6 using aqueous NaOH solution and washed with ethyl acetate. The aqueous layer is adjusted to pH 12 and extracted with EtOAc. The organic layer is washed with brine, dried with MgSO4, filtered, and concentrated. Purification by reversed phase HPLC is giving the title compound, [M+H]+=422; 1H-NMR (400 MHz, CD3OD): δ 9.20 (s, 1H), 9.06-9.03 (m, 2H), 8.74 (d, 1H), 8.67 (t, 1H), 8.04 (d, 1H), 7.99 (d, 1H), 7.23 (d, 1H), 4.41 (m, 2H), 3.76 (m, 2H), 3.60 (m, 2H), 3.43 (m, 2H), 3.04 (s, 3H), 3.03 (s, 3H).

1. temperatureis refluxed for 5 h
2. temperaturecooled down
3. customquenched by addition of aqueous HCl solution (2M, 5 ml)
4. washwashed with ethyl acetate
5. extractionextracted with EtOAc
6. washThe organic layer is washed with brine
7. dry with materialdried with MgSO4
8. filtrationfiltered
9. concentrationconcentrated
10. customPurification by reversed phase HPLC