反应详情

温度

23 °C

A mixture of 2-chloro-6-methoxypyridine (compound 12; 2.87 g, 20 mmol) and anhydrous hydrazine (11 mL, excess) was heated under argon on a steam bath overnight. The mixture was allowed to cool to 23° C. and then was extracted with Et2O (10×10 mL). The combined ether extracts were rotary evaporated to afford 1.58 g (57%) of 2-hydrazino-6-methoxypyridine 13 as a yellow liquid that was -95% pure by NMR: 1H NMR (CDCl3) δ 7.38 (pseudo-t, 1), 6.20 (d, J=8.0 Hz, 1), 6.09 (d, J=8.0 Hz, 1), 5.71 (bs, 1, exchanges upon addition of D2O, NH), 3.84 (s, 3, OCH3), 3.1 (bs, 2, exchanges upon addition of D2O, NH2). A solution of this hydrazine (1.58 g, 11 mmol) in 10 mL of absolute ethanol was combined with a solution of 1 (1.8 g, 10 mmol) in 20 mL of absolute ethanol, and the reaction mixture produced a precipitate within several minutes. The mixture was allowed to stand at 23° C. overnight. The solid was collected by suction filtration, washed with a small amount of ethanol, and was dried in vacuo, giving 1.65 g of the methoxy precursor 14. An additional 510 mg of this precipitated from the filtrate after it had been concentrated on a rotary evaporator to a small volume. Combined yield: 2.15 g (76%): mp 161-162° C. (ethanol). 1H NMR ((CD3)2SO) δ 10.45 (s, 1, exchanges upon addition of D10, OH), 8.25 (s, 1, H4), 8.04 (d, J=8.2 Hz, 1), 7.88 (pseudo-t, 1), 7.54 (d, J=8.2 Hz, 1), 7.36 (s, 1), 7.26 (d, J=8.25 Hz, 1), 6.68 (d, J=7.9 Hz, 1), 6.64 (pseudo-t, 1), 3.92 (s, 3, OCH3), 3.90 (s, 3, OCH3). Low-resolution DCI mass spectrum, m/z 284 (100%, MH+). Exposure of this compound to molten C5H5N○HCl for 10 min effected removal of the hydroxy pyridine protecting group only, by 1H NMR. Exposure to BBr3 in CH2Cl2 solution at 23° C. overnight effected the removal of the phenolic protecting group only, giving 15: mp 198-199° C. (ethanol). 1H NMR ((CD3)2SO) δ 8.17 (s, 1, H4), 7.98 (d, 1), 7.88 (pseudo-t, 1), 7.54 (d, 1), 7.12 (m, 3), 6.67 (d, 1), 3.92 (s, 3, OCH3). Low-resolution DCI mass spectrum, m/z 270 (100%, MH+). X-ray quality crystals of 15 were grown from absolute ethanol and a crystal structure determination was made; the crystal structure of the compound is shown in FIG. 1.

1. temperaturewas heated under argon on a steam bath overnight
2. extractionwas extracted with Et2O (10×10 mL)
3. customThe combined ether extracts were rotary evaporated