反应详情

Step 3—Synthesis of d: tert-butyl 2-(4-(3-ethylureido)phenyl)-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (c, 1.74 mmol) was dissolved in dichloromethane (5 mL), then TFA (3 mL) was added. The mixture was stirred at room temperature for 2 hours. Isopropanol and toluene were added and the resulting mixture was concentrated in vacuo. The resulting residue was azeotroped with toluene two more times. Methanol and methylene chloride (4 mL each) were added to the resulting residue, then PS-carbonate (2.5-3.5 mmol N/gram resin, 1.45 g) was added. The mixture was stirred at room temperature until the pH reached >7 (˜1 hr). The mixture was filtered, the resin was washed with methanol and dichloromethane. The filtrate was concentrated to provide 1-ethyl-3-(4-(4-morpholino-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea as a free amine, which was used in the next step. An aliquot was purified by reverse-phase HPLC to give the pure desired product: 1H NMR (400 MHz, DMSO) δ 9.57 (s, 1H), 8.75 (s, 1H), 8.19 (d, J=8.9, 2H), 7.50 (d, J=8.9, 2H), 6.38-6.08 (m, 1H), 4.71 (s, 2H), 4.38 (s, 2H), 3.72 (s, 8H), 3.24-3.03 (m, 2H), 1.06 (t, J=7.2, 3H); LC-MS: m/z=+369 (M+H)+.

1. concentrationthe resulting mixture was concentrated in vacuo
2. customThe resulting residue was azeotroped with toluene two more times
3. additionMethanol and methylene chloride (4 mL each) were added to the resulting residue
4. stirringThe mixture was stirred at room temperature until the pH
5. custom>7 (˜1 hr)
6. filtrationThe mixture was filtered
7. washthe resin was washed with methanol and dichloromethane
8. concentrationThe filtrate was concentrated