Triethylamine → 3-[4-(Azetidin-1-ylcarbonyl)-2,5-difluorophenoxy]-5-[(1S)-2-hydroxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide

Temperature

160 °C

A solution of 2,4,5-trifluorobenzoic acid (123 mg, 0.7 mmol) in DCM (1.7 mL) was treated with (1-chloro-2-methylprop-1-en-1-yl)dimethylamine (103 mg, 0.77 mmol) and stirred under argon for 1 hour. The mixture was then treated with triethylamine (0.29 mL, 2.1 mmol) and azetidine hydrochloride (78 mg, 0.84 mmol), before being left to stir for 18 hours. The mixture was diluted with DCM (5 mL) and 2M hydrochloric acid (4 mL) and separated. The organic layer was dried (MgSO4), filtered and concentrated in vacuo. The residue was treated with suspension of 3-hydroxy-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide (200 mg, 0.477 mmol) and potassium carbonate (284 mg, 2.05 mmol) in acetonitrile (3.5 mL) was heated in a microwave reactor at 160° C. for 1.5 hours. The reaction mixture was filtered and concentrated in vacuo. The residue was then chromatographed on silica, eluting with 0-15% methanol in ethylacetate, to give the title compound (74 mg).

1. waitbefore being left
2. stirringto stir for 18 hours
3. customseparated
4. dry with materialThe organic layer was dried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. filtrationThe reaction mixture was filtered
8. concentrationconcentrated in vacuo
9. customThe residue was then chromatographed on silica
10. washeluting with 0-15% methanol in ethylacetate

ORD record

ord-ef98e1c7b4764eec9a3f724e10aa14e9

Source dataset

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07745475B2