Dimethyl Sulfoxide → HCID 178521587, compound

Temperature

75 °C

To 5-chloro-2-fluoro-4-iodopyridine (600 mg, 2.331 mmol) was added DMSO (2.2 ml), trans-4-aminocyclohexanol (1074 mg, 9.32 mmol) and TEA (0.390 ml, 2.80 mmol). The resulting reaction mixture was stirred at 75° C. for 24 hr, followed by LCMS. The reaction mixture was cooled to room temperature, mixed with 150 ml of ethyl acetate, washed with saturated sodium bicarbonate (1×), water (1×), saturated salt solution (1×), dried over sodium sulfate, filtered and concentrated to yield a crude material. The crude material was purified by silica gel chromatography using a 40 g column eluting from 15%-75% ethyl acetate with hexane. The desired fractions were combined and concentrated to constant mass, giving 750 mg of the title compound as free base, which was used in the next step without further purification. LCMS (m/z): 353.0 (MH+), retention time=0.56 min.

1. customThe resulting reaction mixture
2. temperatureThe reaction mixture was cooled to room temperature
3. washwashed with saturated sodium bicarbonate (1×), water (1×), saturated salt solution (1×)
4. dry with materialdried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. customto yield a crude material
8. customThe crude material was purified by silica gel chromatography
9. washeluting from 15%-75% ethyl acetate with hexane
10. concentrationconcentrated to constant mass

ORD record

ord-4e15243b3f3c4673aae7ec82a3fef408

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08415381B2