Trimethyl orthoformate → HCID 68516158, compound

Participants

Reaction Steps

A stirred mixture of trimethoxymethane (118 mL, 1077 mmol) and 2,2-dimethyl-1,3-dioxane-4,6-dione (Meldrum's acid) (15.5 g, 108 mmol) was heated under reflux for 1 hour. A suspension of 1-(4-methoxybenzyl)-3-methyl-1H-pyrazol-5-amine (23.4 g, 108 mmol; prepared according to the procedure described by Misra, R. N.; et al. Bioorg. Med. Chem. Lett. 2003, 13, 1133-1136) in trimethyl orthoformate (110 mL, 1075 mmol) was added at once, and the dark orange reaction was refluxed for 3 hours under N2. After cooling to room temperature, the reaction was concentrated in vacuo, using toluene (3×100 mL) to azeotrope residual trimethyl orthoformate. The resulting deep orange residue was triturated/sonicated with diethyl ether (200 mL). The resulting peach colored solid was filtered, washing with diethyl ether (3×50 mL). Yield: 28.0 g, 70%. 1H NMR (400 MHz, DMSO-d6) δ 11.13 (d, J=11 Hz, 1H), 8.06 (d, J=11 Hz, 1H), 7.10 (d, J=9 Hz, 2H), 6.87 (d, J=9 Hz, 2H), 6.32 (s, 1H), 5.19 (s, 2H), 3.70 (s, 3H), 2.14 (s, 3H), 1.65 (s, 6H).

Provenance & Evidence