Hydrazine hydrate (1:1) → HCID 90011255, compound

Participants

Reaction Steps

Step-1: 1-(5-Bromopyridin-2-yl)-3-(furan-2-yl)-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-ol: To a stirred solution of 1,1,1-trifluoro-4-(furan-2-yl)-4-methoxybut-3-en-2-one (129 g, 585 mmol; prepared by following the procedure described in Tett Lett., 2002, 43, 8701) in chloroform (600 mL) was added solid 5-bromo-2-hydrazinylpyridine (prepared by the reaction of 2,5-dibromopyridine with hydrazine hydrate, 110.0 g, 585 mmol) in 10 portions at 0° C. over a period of 30 min. The reaction was stirred for 1 h at room temperature, and then at 50° C. for 36 h. The reaction was cooled to 0° C. before the addition of water (200 mL) and chloroform (500 mL). The layers were separated and the aqueous layer was extracted with chloroform (3×200 mL). The combined organic layers were washed with brine (200 mL), dried (Na2SO4) and filtered. The filtrate was rotary evaporated and the crude product was purified by flash column chromatography (5% ethyl acetate-hexanes system as eluent) to afford 90 g (40%) of the title compound as a white solid. 1HNMR (400 MHz, CDCl3) δ 8.17 (d, J=2.5 Hz, 1H), 7.96 (s, 1H, D2O Exchangeable), 7.75 (dd, J=2.5 & 8.5 Hz, 1H), 7.56 (d, J=1.5 Hz, 1H), 7.41(d, J=8.5 Hz, 1H), 6.76 (d, J=2.5 Hz, 1H), 6.54 (dd, J=1.5 & 2.5 Hz, 1H), 3.71(d, J=18.5 Hz, 1H), 3.56 (d, J=18.5 Hz, 1H); ESI-MS (m/z) 376, 378 [(MH)+, Br79,81].

Provenance & Evidence