反应详情

4-[4-amino-5-(4-amino-3-methoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-1-cyclohexanone (2.25 g, 6.5 mmol), acetic acid (1.17 g, 19.5 mmol) and N-methylpiperazine (1.95 g, 19.5 mmol) were dissolved in dichloroethane (200 ml). Sodium triacetoxyborohydride (2.07 g, 9.75 mmol) was added portionwise and the mixture stirred at room temperature overnight. Saturated sodium bicarbonate solution (150 ml) was added and the aqueous layer extracted with dichloromethane (3×100 ml). The combined organics were washed with water, dried (sodium sulphate), filtered and evaporated to leave a semi-solid whaich was purified by flash silica gel column chromatography using CH2Cl2/methanol (0% MeOH to 50% MeOH in 5% increments). The fractions corresponding to the faster running material were combined and evaporated to give cis-5-(4-amino-3-methoxyphenyl)-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine (1.2 g, 43%) as a cream solid. 1H NMR (d6-DMSO): δ 8.1(1H, s), 7.11(1H, s), 6.87(1H, s), 6.79(1H, d), 6.05(2H, bs), 4.80(2H, bs), 4.64(1H, m), 4.08(1H, m), 3.82(3H, s), 3.17(2H, m), 2.37(6H, m), 2.21(3H, s), 2.08(4H, m), 1.70(2H, m), 1.53(2H, m). HPLC (rt=11.24 min, 97.6%).

1. extractionthe aqueous layer extracted with dichloromethane (3×100 ml)
2. washThe combined organics were washed with water
3. dry with materialdried (sodium sulphate)
4. filtrationfiltered
5. customevaporated
6. customto leave a semi-solid
7. customwas purified by flash silica gel column chromatography
8. customevaporated