Lithium Hexamethyldisilazide → HCID 86723324, compound

To a solution of 2-chloro-3-fluoro-pyridin-4-amine (3.31 g, 22.6 mmol) in THF (50 mL) at 0° C. was slowly added LiHMDS in THF (1.0 M, 45 mL). The mixture was warmed to room temperature and allowed to stir for 1 hour. It was then cooled to −78° C. A THF solution of 2-chloro-6-fluoro-4-iodo-benzoyl chloride (15.1 mmol, 15 mL) was added dropwise. The mixture was stirred at −78° C. for 1 hour. The reaction was then quenched with sat. NH4Cl, extracted with EtOAc (3×). The combined organics were dried over Na2SO4, concentrated. The crude product was purified by silica gel column chromatography (0-25% EtOAc/hexane) to give the title compound (4.97 g, 76.8% yield) as an off-white solid. 1H NMR (400 MHz, methanol-d4) δ 8.37 (t, J=5.4 Hz, 1H), 8.18 (d, J=5.5 Hz, 1H), 7.80 (s, 1H), 7.69 (dd, J=8.2, 1.2 Hz, 1H). LCMS (ESI) m/z 429.0 [M+H+].

1. customat 0° C.
2. temperatureIt was then cooled to −78° C
3. stirringThe mixture was stirred at −78° C. for 1 hour
4. customThe reaction was then quenched with sat. NH4Cl
5. extractionextracted with EtOAc (3×)
6. dry with materialThe combined organics were dried over Na2SO4
7. concentrationconcentrated
8. customThe crude product was purified by silica gel column chromatography (0-25% EtOAc/hexane)

ORD record

ord-ba65b0c381bb41e19ea1ab2b1d8fbc48

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08697708B2