Reaction Steps
A mixture of (3S-trans)-4-amino-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (0.65 g, 0.0030 mol, compound of Example 1, part B) and the compound of title B (1.37 g, 0.0042 mol) in acetonitrile (20 mL) and dimethylformamide (30 mL) was heated at 80° C. for two hours. The reaction mixture was concentrated in vacuo and the residue, diluted with ethyl acetate, was washed with 10% citric acid and water. The organic layer was dried over MgSO4 and concentrated in vacuo. The product was purified by flash chromatography (Sorbisol C 60 flash silica gel, 400 mL) and eluted with hexanes/EtOAc (2:1) and hexanes/EtOAc (1:1). The solvent was removed in vacuo, to give a solid that was triturated with anhydrous ether and dried in vacuo to yield 0.75 g (70%) of the title compound, m.p. 162°-167° C. TLC, silica gel, EtOAc/hexanes (2:1), Rf =0.34. 1H-NMR (DMSO-d6) δ9.2 (s, 1H), 9.0 (s, 1H), 8.0 (d, J=8.8 Hz, 2H), 7.7 (d, J=8.8 Hz, 2H), 7.6 (m, 2H), 7.0 (d, J=9.4 Hz, 1H), 5 6.8 (d, J=8.8 Hz, 1H), 5.7 (s, 1H), 4.7 (t, J=8.8 Hz, 1H), 3.7 (dd, J=5.9 & 3.5 Hz, 1H), 1.4 (s, 3H), 1.2 (s, 3H); 13C-NMR (DMSO-d6) δ174.6, 158.4, 156.3, 155.4, 145.0, 132.6, 129.0, 125.7, 119.1, 117.9, 117.8, 115.7, 102.7, 80.4, 71.3, 49.5, 26.5, 18.9; IR (KBr) 2226, 1672, 1603, 1539, 1462 cm-1M.S. (M+H)+ at 406, M.W. 405; [α]D =-76.2° (c=0.86 DMSO).
