Tetrahydrofuran → HCID 178465139, compound

Temperature

5 °C

A 500-mL 3-neck flask was charged with 3-chloro-N-ethyl-1H-pyrazol-4-amine (3.25 g, 22.3 mmol), tetrahydrofuran (80 mL) and water (80 mL). The resulting suspension was cooled to 5° C. and sodium bicarbonate (3.75 g, 44.6 mmol) was added, followed by dropwise addition of 3-((3,3,3-trifluoropropyl)thio)propanoyl chloride (5.42 g, 24.56 mmol) at <5° C. The reaction mixture was stirred at <10° C. for 3 hours. The reaction mixture was poured into water (100 mL) and the mixture was extracted with dichloromethane (150 mL×3). The combined organics were washed with water (200 mL) and brine (200 mL), dried over anhydrous sodium sulfate (Na2SO4), filtered, and concentrated under reduced pressure to afford crude product as a light brown oil, which was purified by flash column chromatography using 0-5% methanol/dichloromethane as eluent. The fractions containing pure product were concentrated to give the desired product as a white solid (3.60 g, 48%): mp 67-68° C.; 1H NMR (400 MHz, CDCl3) δ 11.55 (bs, 1H), 7.65 (s, 1H), 3.73-3.68 (dd, J1=7.2, J2=14.0, 2H), 2.86-2.82 (t, J=7.2, 2H), 2.67-2.63 (t, J=8.0, 2H), 2.45-2.30 (m, 4H), 1.16-1.12 (t, J=7.2, 3H); 13C NMR (101 MHz, CDCl3) δ 171.87, 137.89, 128.40, 125.97 (q, J=277.4 Hz), 120.81, 44.01, 34.31 (q, J=27.3 Hz), 33.97, 27.30, 24.08 (q, J=3.4 Hz), 12.77; ESIMS m/z 330 ([M+H]+).

1. extractionthe mixture was extracted with dichloromethane (150 mL×3)
2. washThe combined organics were washed with water (200 mL) and brine (200 mL)
3. dry with materialdried over anhydrous sodium sulfate (Na2SO4)
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customto afford crude product as a light brown oil, which
7. customwas purified by flash column chromatography
8. additionThe fractions containing pure product
9. concentrationwere concentrated

ORD record

ord-ef3ddf59019d4fc8a3e3eea0727701d9

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09029554B1