Trifluoroacetic acid → HCID 86720961, compound

Temperature

80 °C

Tert-butyl carbamate (211.3 mg, 1.804 mmol), sodium tert-butoxide (173.4 mg, 1.804 mmol), BrettPhos Pre-catalyst (143.7 mg, 0.1804 mmol) and BrettPhos (96.83 mg, 0.1804 mmol) were degassed by vacuum/nitrogen cycles (×5). A solution of 1-[[1-(3-chloro-5-fluoro-4-pyridyl)-4-piperidyl]sulfonyl]-4-methyl-piperazine (340 mg, 0.9022 mmol) in dry toluene (9.884 mL) was added and the resulting mixture was heated to 80° C. After 5 minutes at 80° C. the reaction was cooled to RT and partitioned between ethyl acetate and water. The combined organics was dried with MgSO4 and concentrated in vacuo to a yellow solid. The yellow solid was purified by column chromatography using 1% MeOH/DCM to elute side products and then 5-10% MeOH/DCM to elute product. Relevant fractions combined and concentrated in vacuo to yield a light yellow solid. It was dissolved in DCM (10 mL) followed by the addition of TFA (1.029 g, 695.3 μL, 9.022 mmol). The mixture was stirred at room temperature for 2 hours. The mixture was concentrated in vacuo to yield 5-fluoro-4-(4-((4-methylpiperazin-1-yl)sulfonyl)piperidin-1-yl)pyridin-3-amine as a light orange solid. MS (ES+) 358.1.

1. temperatureAfter 5 minutes at 80° C. the reaction was cooled to RT
2. custompartitioned between ethyl acetate and water
3. dry with materialThe combined organics was dried with MgSO4
4. concentrationconcentrated in vacuo to a yellow solid
5. customThe yellow solid was purified by column chromatography
6. washto elute side products
7. wash5-10% MeOH/DCM to elute product
8. concentrationconcentrated in vacuo
9. customto yield a light yellow solid
10. concentrationThe mixture was concentrated in vacuo

ORD record

ord-2d0478087a3b4b2cbc0834917b29aa58

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09340546B2