Cesium carbonate → Methyl 3-[5-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-3,4-dihydro-2(1H)-isoquinolinyl]propanoate formic acid salt

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Reaction Steps

A suspension of 2-[(1-methylethyl)oxy]-5-[3-(1,2,3,4-tetrahydro-5-isoquinolinyl)-1,2,4-oxadiazol-5-yl]benzonitrile (Example 3, 28.8 mg, 0.080 mmol), methyl 3-bromopropionate (35 μl, 0.32 mmol) and Cs2CO3 (130 mg, 0.40 mmol) in DMF (2 mL) was stirred at room temperature for 1 h, and then irradiated to 60° C. for 5 min in the microwave. More methyl 3-bromopropionate (35 μl, 0.32 mmol) was added and the suspension was stirred at room temperature for 3.5 h, and then irradiated to increasing temperatures in the microwave until 150° C. for 30 min was achieved. The suspension was filtered and concentrated in vacuo then purified by MDAP to give the title compound as a yellow film (5.9 mg, 17%). 1H NMR (400 MHz, CDCl3) δ 8.42 (1H, d), 8.33 (1H, dd), 8.21 (1H, br. s), 8.04 (1H, d), 7.35 (1H, t), 7.24 (1H, d), 7.13 (1H, d), 4.80 (1H, sept), 3.99 (2H, s), 3.72 (3H, s), 3.38 (2H, t), 3.12-3.06 (4H, m), 2.78 (2H, t), 1.48 (6H, d); m/z (ES) 447 [M+H]+.

Provenance & Evidence