反应详情

温度

120 °C

3-(2-Methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine (76 mg, 0.34 mmol, 1.0 eq), N-[2-(2,5-dichloro-pyrimidin-4-ylamino)-2-methyl-propyl]-methanesulfonamide (119 mg, 0.38 mmol, 1.1 eq), and 10-camphorsulfonic acid (88 mg, 0.38 mmol, 1.1 eq) were dissolved in IPA (3 mL) and heated at 120° C. in a microwave for 40 minutes. The reaction was then concentrated under reduced pressure and the residue was taken up in CH2Cl2 (20 mL) and washed with sat. NaHCO3 (20 mL). The organic layer was dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by amine capped silica gel chromatography using a gradient of 0-100% EtOAc/hex as the eluting solvent to obtain N-(2-{5-chloro-2-[3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-2-methyl-propyl)-methanesulfonamide as a white foam (107 mg, 63%). LCMS (m/e) 497 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 7.94 (s, 1H), 7.25-7.18 (m, 2H), 7.04 (d, 1H, J=7.9 Hz), 6.87 (s 1H), 5.93-5.79 (m, 1H), 5.13 (s, 1H), 3.55 (t, 2H, J=5.7 Hz), 3.47 (d, 2H, J=6.0 Hz), 3.38 (s, 3H), 2.99-2.88 (m, 4H), 2.78 (s, 3H), 2.81-2.68 (m, 6H), 1.50 (s, 6H).

1. concentrationThe reaction was then concentrated under reduced pressure
2. washwashed with sat. NaHCO3 (20 mL)
3. dry with materialThe organic layer was dried (sodium sulfate)
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customPurification by amine
7. customcapped silica gel chromatography