Reaction Steps
To a solution of 3-(1-adamantyl)-4-benzyloxyphenylboronic acid (Zhang Y. et al., Blood, 2002; 100:2917-2925, Dawson M. I. et al., J. Med. Chem., 2004; 47:3518-3536) (3.62 g, 10.0 mmol) and ethyl (2E)-3-(2-chloro-5-pyrimidinyl)-2-propenoate (1.76 g, 8.30 mmol) in dimethoxyethane (50 mL) was added under argon tetrakis(triphenylphosphine)-palladium (1.15 g, 1.00 mmol) and 2 M aqueous Na2CO3 (10 mL). The reaction mixture was heated at reflux for 18 h, cooled to room temperature, diluted with ethyl acetate, washed (water and brine) and dried. After solvent removal at reduced pressure, the residue was chromatographed (9% to 14% ethyl acetate/hexane) to give 3.98 g (96%) of ethyl(E)-3-[2-(3-(1-adamantyl)-4-benzyloxyphenyl)-5-pyrimidinyl]-2-propenoate as a yellow solid, mp 164-167° C. IR 2903, 1710, 1432, 1225 cm−1; 1H NMR δ (CDCl3) 1.40 (t, J=7.2 Hz, 3H, OCH2CH3), 1.77 (bs, 6H, AdCH2), 2.11 (bs, 3H, AdCH), 2.26 (bs, 6H, AdCH2), 4.33 (q, J=7.2 Hz, 2H, OCH2CH3), 5.24 (s, 2H, CH2), 6.59 (d, J=16.2 Hz, 1H, CH═CHCO), 7.08 (d, J=8.7 Hz, 1H, 5-ArH), 7.35-7.58 (m, 5H, C6H5), 7.65 (d, J=16.2 Hz, 1H, CH═CHCO), 8.33 (dd, J=8.7 Hz, 2.1 Hz, 1H, 6-ArH), 8.47 (d, J=2.1 Hz, 1H, 2-ArH), 8.91 ppm (s, 2H, 4-PyrH, 6-PyrH). HRMS calcd C32H34N2O3 [M+H]+ 495.2642. found 495.2636.
