反应 #48877

反应方程式

2,4,5-trifluorobenzoic acid

(1-chloro-2-methylprop-1-en-1-yl)dimethylamine

triethylamine

azetidine hydrochloride

3-hydroxy-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide

potassium carbonate

→

title compound

收率 31.9%

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

收率 31.9%

溶剂

DCM

hydrochloric acid

DCM

acetonitrile

反应条件

后处理

1. 1
   workup.WAITbefore being left
2. 2
   workup.STIRRINGto stir for 18 hours
3. 3
   其他separated
4. 4
   干燥The organic layer was dried (MgSO4)
5. 5
   过滤filtered
6. 6
   浓缩concentrated in vacuo
7. 7
   过滤The reaction mixture was filtered
8. 8
   浓缩concentrated in vacuo
9. 9
   其他The residue was then chromatographed on silica
10. 10
    洗涤eluting with 0-15% methanol in ethylacetate

实验过程

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).

来源