反应详情

Followed the procedure described in General Scheme II, with modification. Step 1 was followed where the starting material was N-(4-(4-bromo-2-formylthiophen-3-yl)-3-methylphenyl)methanesulfonamide (Intermediate 4) instead of 3,4-dibromothiophene-2-carbaldehyde (Intermediate I), starting material 8A was 4-chloro-2-methoxyphenylboronic acid. After purification by column chromatography (PE:EtOAc=3:1) N-(4-(4-(4-chloro-2-methoxyphenyl)-2-formylthiophen-3-yl)-3-methylphenyl)methanesulfonamide (380 mg, yield 365.2%) was obtained. Step 3 of Scheme II was then followed with column conditions (PE: EtOAc=3:1) to afford (E)-ethyl 3-(4-(4-chloro-2-methoxyphenyl)-3-(2-methyl-4-(methylsulfonamido)phenyl)thiophen-2-yl)acrylate (280 mg, yield 63.4%). Step 4 of Scheme II gave 200 mg of product (yield 71%) followed by Step 5 (with purification by prep-HPLC) gave Example 10 (41.9 mg, 13% yield). 1H NMR (DMSO-d6 400 MHz): δ 9.73 (s, 1H), 7.38 (s, 1H), 6.93 (m, 4H), 6.90 (s, 1H), 6.86 (m, 1H), 3.5 (d, 3H), 2.95 (s, 1H), 2.75 (m, 2H), 7.01 (t, J=7.2 Hz, 2H), 1.82 (s, 3H); MS (ESI): m/z 502.0 [M+23]+.