反应详情

To a solution of ethyl ((1S)-5-{3-[(5-bromo-2-pyrimidinyl)amino]propoxy}2,3-dihydro-1H-inden-1-yl)acetate (Example 281, 500 mg, 1.15 mmol) in DMF (10 mL) was added NaH [H2 evolution], followed by Mel (180 mg, 1.27 mmol) added over 5 min. The reaction mixture was stirred at rt for 4 h, NH4Cl (10% aqueous solution) was added, after which the mixture was concentrated under reduced pressure. The residue was taken up in EtOAc, then washed with water and brine successively. The organic phase was dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography to provide the product (600 mg, 21%) as a colorless oil. 1H NMR (300 MHz, CDCl3) δ 1.29 (t, 3H), 1.71-1.81 (m, 1H), 2.05-2.13 (m, 2H), 2.34-2.45 (m, 2H), 2.73 (dd, 1H), 2.73-2.94 (m, 2H), 3.14 (s, 3H), 3.49-3.56 (m, 1H), 3.77 (t, 2H), 3.97 (t, 2H), 4.18 (q, 2H), 6.74 (dd, 1H), 6.75 (d, 1H), 7.05 (d, 1H), 8.24 (s, 2H).

1. additionadded over 5 min
2. concentrationafter which the mixture was concentrated under reduced pressure
3. washwashed with water and brine successively
4. dry with materialThe organic phase was dried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified by silica gel chromatography