Hydrochloric Acid → HCID 68756556, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of methyl 4-(bromomethyl)benzoate (4.58 g, 20 mmol) and trimethyl phosphite (3.54 mL, 30 mmol) was refluxed (oil temp. 125° C.) for 1 h under argon. After cooling to rt, the reaction mixture was diluted with DMF (50 mL) and cooled to 0° C. using ice bath. tBuOK (3.92 g, 35 mmol) was added slowly. After addition, the resulting dark brown solution was stirred for 5 min at 0° C. before a solution of 3-formyl-1H-indazole-6-carbonitrile (2.0 g, 11.7 mmol) in DMF (15 mL) was added dropwise via a pasteur pipette over 5 min. The reaction mixture was then stirred for 90 min at 0° C.; 2N HCl (25 mL) was added slowly over 2 min, followed by H2O (100 mL). The resulting suspension was stirred for 5 min at 0° C. The precipiates collected by suction filtration were rinsed well with H2O and dried to give crude (E)-methyl 4-(2-(6-cyano-1H-indazol-3-yl)vinyl)benzoate (3.70 g) as an orange solid. Trituration with 50 mL of ether, followed by sonication and suction filtration gave pure (E)-methyl 4-(2-(6-cyano-1H-indazol-3-yl)vinyl)benzoate (2.56 g, 72%) as an orange solid. 1H NMR (400 MHz, DMSO-d6) δ 13.83 (s, 1H), 8.43 (d, J=8.8 Hz, 1H), 8.18 (s, 1H), 7.97 (d, J=8.4 Hz, 2H), 7.87 (d, J=8.4 Hz, 2H), 7.76 (d, J=16.4 Hz, 1H), 7.63 (d, J=16.8 Hz, 1H), 7.55 (d, J=8.4 Hz, 1H), 3.86 (s, 3H); MS ESI 304.1 [M+H]+, calcd for [C18H13N3O2+H]+ 304.1.

Provenance & Evidence