Reaction Steps
To a suspension of 2-methoxycarbonyl-5,7-dichloro-4-amino-1,2,3,4-tetrahydroquinoline hydrochloride (Example 9) (300 mg, 0.963 mmol) in anhydrous dichloromethane (15 ml) under an atmosphere of nitrogen was added dry triethylamine (403 μl, 2.89 mol) and the resulting mixture was stirred at room temperature for 5 min. To this was added 3-(tertbutyloxycarbonylamino)methyl benzoic acid (step a) (290 mg, 1.16 mmol), 1-hydroxybenzotriazole (156 mg, 1.16 mol) followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (222 mg, 1.16 mmol) and stirring was continued for approximately 18 h. The mixture was then concentrated in vacuo and the residue partitioned between ethyl acetate (100 ml) and 0.5M citric acid (150 ml). The organic layer was retained and washed successively with 0.5M citric acid (150 ml), saturated sodium bicarbonate solution (2×150 ml) and brine (100 ml) before drying (Na2SO4). The solvent was removed and the residue was recrystallised from ethyl acetate/hexane to give the title compound as colourless crystals (351 mg), m.p. 222°-223° C. δ (DMSO, 250 MHz) 1.39 (9H, s, C(CH3)3), 1.78 (1H, ddd, J=12.8, 12.6 and 3.9 Hz, CHACHBHCCHD), 2.26 (1H, dm, J=12.8 Hz, CHACHBHCCHD), 3.71 (3H, s, COOCH3), 4.05 (1H, dd, J=13.0 and 3.0 Hz, CHACHBHCCHD), 4.14 (2H, d, J=5.8 Hz, ArCH2NH), 5.26 (1H, m, CHACHBHCCHD), 6.69 (1H, d, J=2.1 Hz, 6-H or 8-H), 6.90 (1H, d, J=2.1 Hz, 6-H or 8-H), 6.93 (1H, s, ArNHCH), 7.37 (3H, m, Ar-H and CH2NHCO), 7.71-7.76 (2H, m, Ar-H), 8.68 (1H, d, J=7.1 Hz); m/e 507 (M+), 198 (100%, M-H, CO2CH2CH3,NHCOC6H4CH2NHCOOC(CH3)3).
