反应详情

To a mixture of Compound (7) (34 mg, 67 μmol) and tetrazole acetic acid (10 mg, 81 μmol) in DMF (3 mL) at 0° C. was added HATU (31 mg, 81 μmol) and DIPEA (18 μL, 0.1 mmol). The mixture was stirred at RT for 40 min. Ethyl acetate (5 mL) was added and the mixture was washed with 1M hydrochloric acid and saturated sodium bicarbonate. The combined aqueous phase was neutralised to pH 7 (by addition of 6M hydrochloric acid) and lyophilised. The crude material was then purified by reverse phase flash column chromatography eluting with ACN/water (5-100%) to give Compound (8) (17 mg, 41%). ESI-MS m/z calculated for [M+H]+: 616.11/618.11; found: 615.96/617.96. 1H NMR (400 MHz, d4-MeOH) δ 9.42 (s, 1H), 9.27 (d, J=8.7 Hz, 2H), 9.10 (d, J=8.7 Hz, 2H), 8.87 (s, 1H), 5.55-5.37 (m, 2H), 5.37-5.14 (m, 2H), 5.01 (t, J=6.5 Hz, 2H), 4.70 (s, 3H), 4.52 (s, 3H), 3.95-3.73 (m, 1H), 2.69-2.41 (m, 3H), 2.27-2.10 (m, 1H).

1. washthe mixture was washed with 1M hydrochloric acid and saturated sodium bicarbonate
2. additionThe combined aqueous phase was neutralised to pH 7 (by addition of 6M hydrochloric acid)
3. customThe crude material was then purified by reverse phase flash column chromatography
4. washeluting with ACN/water (5-100%)