Lithium Hydroxide → N-[(1S,2S)-2-[[2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-pyrimidin-4-yl]amino]cyclohexyl]acetamide

(1S,2S)—N-[2-[5-chloro-1-(p-tolylsulfonyl)pyrrolo[5,4-b]pyridin-3-yl]-5-fluoro-pyrimidin-4-yl]cyclohexane-1,2-diamine, 15b, (0.100 g, 0.194 mmol) was dissolved in dichloromethane (2 mL) and treated with iPr2NEt (0.075 g, 0.101 mL, 0.583 mmol). Acetyl chloride (0.021 mL, 0.291 mmol) was added and the reaction was allowed to stir at room temperature for 30 minutes. The volatiles were evaporated under reduced pressure, and the residue was dissolved in dichloroethane (2 mL) and treated with LiOH (0.097 mL of 1 M solution, 0.971 mmol). The reaction mixture was heated in the microwave at 150° C. for 10 minutes. The reaction was diluted with EtOAc (5 mL) and water (5 mL) and the layers were separated. The aqueous layer was extracted with EtOAc (2×5 mL), and the combined organic extracts were dried over Na2SO4 and concentrated in vacuo to provide the crude product, which was purified by silica gel chromatography (0%-15% MeOH/CH2Cl2) to provide N-[(1S,2S)-2-[[2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-pyrimidin-4-yl]amino]cyclohexyl]acetamide, 433, (34 mg, 44% yield).

1. customThe volatiles were evaporated under reduced pressure
2. dissolutionthe residue was dissolved in dichloroethane (2 mL)
3. temperatureThe reaction mixture was heated in the microwave at 150° C. for 10 minutes
4. customthe layers were separated
5. extractionThe aqueous layer was extracted with EtOAc (2×5 mL)
6. dry with materialthe combined organic extracts were dried over Na2SO4
7. concentrationconcentrated in vacuo
8. customto provide the crude product, which
9. customwas purified by silica gel chromatography (0%-15% MeOH/CH2Cl2)

ORD record

ord-9c2d4743c51948c0a6f60ff9d3635ade

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08829007B2