Sodium hydride → ethyl ((1S)-5-{3-[(5-bromo-2-pyrimidinyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate

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Reaction Steps

To a solution of 5-bromo-2-aminopyrimidine (2.35 g, 13.5 mmol) in DMF (50 mL) was added NaH (539 mg, 13.5 mmol of a 60% dispersion in mineral oil) [H2 evolution]. Then, ethyl [(1S)-5-(3-bromopropoxy)-2,3-dihydro-1H-inden-1-yl]acetate (Example 45, 2.3 g, 6.74 mmol) was added over 5 min, and the reaction mixture was stirred at rt for 4 h, after which NH4Cl (10% aqueous solution) was added, and the mixture was concentrated under reduced pressure. The residue was taken up in EtOAc and 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 (400 MHz, CDCl3) δ 1.27 (t, 3H), 1.70-1.81 (m, 1H), 2.02-2.12 (m, 2H), 2.34-2.43 (m, 1H), 2.41 (dd, 1H), 2.73 (dd, 1H), 2.77-2.94 (m, 2H), 3.48-3.56 (m, 1H), 3.58 (q, 2H), 4.03 (t, 2H), 4.18 (q, 2H), 5.95 (b t, 1H), 6.69 (dd, 1H), 6.75 (d, 1H), 7.04 (d, 1H), 8.22 (s, 2H).

Provenance & Evidence