反应详情

A solution of (1S)-7-amino-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonyl-ethyl]-2,3-dihydro-isoindol-1-one (0.5 g, 1.2 mmol) and 2-methoxyacetyl chloride (0.3 mL, 3.2 mmol) in THF (6 mL) was heated to reflux for 17 hours. To the mixture was added methanol (5 mL). The solvent was removed in vacuo to give a solid, which was purified with Prep HPLC to give (1S)-N-{2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonyl-ethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}-2-methoxy-acetamide as an off-white solid (180 mg, 32% yield): mp 151-153° C.; 1H NMR (CDCl3) δ 1.47 (t, J=7 Hz, 3H, CH3), 2.84 (s, 3H, CH3), 3.56 (s, 3H, CH3), 3.77 (dd, J=5, 14 Hz, 1H, CHH), 3.85 (s, 3H, CH3), 4.08 (s, 2H, CH2), 4.12 (q, J=7 Hz, 2H, CH2), 4.53 (dd, J=10, 15 Hz, 1H, CHH), 5.87 (dd, J=5, 10 Hz, 1H, NCH), 6.81-6.82 (m, 1H, Ar), 7.10-7.13 (m, 2H, Ar), 7.51 (d, J=7 HZ, 1H, Ar), 7.67 (t, J=8 Hz, 1H, Ar), 8.81 (d, J=8 Hz, 1H, Ar), 10.42 (s, 1H, NH); 13C NMR (CDCl3) δ 14.69, 41.59, 48.80, 54.81, 55.96, 59.74, 64.55, 72.18, 111.49, 112.53, 116.06, 118.59, 120.49, 125.09, 129.39, 131.33, 136.02, 136.59, 148.62, 149.77, 167.57, 168.89, 169.16. Analy. calculated for C23H26N2O8S: C, 56.32; H, 5.34, N 5.71. Found: C, 56.23; H, 5.30; N, 5.56.

1. temperatureto reflux for 17 hours
2. customThe solvent was removed in vacuo
3. customto give a solid, which
4. customwas purified with Prep HPLC