Reaction Steps
The crude (3-amino-6-methyl-2-oxo-2,3,4,7-tetrahydroazepin-1-yl}-acetic acid ethyl ester, 10, obtained in the previous step is dissolved in 6 mL of 1:1 DMF:CH2Cl2 and treated with 1-isoquinolinecarboxylic acid (0.24 g, 1.2 mmol), 1-hydroxybenzotriazole (0.23 g, 1.5 mmol), and 1-(3-dimethyl-aminopropyl)-3-ethyl-carbodiimide hydrochloride (0.32 g, 1.5 mmol). The solution is stirred for 1 hour at room temperature, diluted with EtOAc, washed with saturated NaHCO3, saturated NaCl, and dried (Na2SO4). The solvent is removed in vacuo and the crude isolate is purified by HPLC to afford 70 mg (30% yield) of the desired product. 1H NMR (CDCl3) δ 9.51–9.48 (d, J=8.1 Hz, 1H), 9.22–9.20 (d, J=6.9 Hz, 1H), 8.51–8.49 (d, J=5.4 Hz, 1H), 7.84–7.77 (m, 2H), 7.72–7.63 (m, 2H), 5.57 (bs, 1H), 5.48–5.40 (m, 1H), 4.775–4.715 (d, J=18 Hz, 1H), 4.24–4.19 (q, d, J=15.3, 7.5 Hz, 3H), 3.27–3.21 (d, J=18 Hz, 1H), 2.86–2.81 (d, J=16.5 Hz, 1H), 2.45–2.36 (d, d, J=15, 12.6 Hz, 1H), 1.79 (s, 3H), 1.30–1.25 (t, J=7.5 Hz, 3H); 13C (CDCl3) 172.8, 169.2, 165.6, 148.2, 140.8, 137.5, 131.8, 130.5, 128.7, 127.7, 127.0, 124.5, 123.4, 61.6, 52.3, 50.8, 49.6, 32.6, 25.0, 14.3; MS 382 (M+H)+.
