Methanol → HCID 90092735, compound

Under nitrogen atmosphere, to a solution of 4-(3,4-dihydro-2H-1-benzopyran-6-yl)-1-methyl-3-(pyridin-2-yl)-1H-pyrazole-5-carbaldehyde (9f) (137 mg, 0.43 mmol) in anhydrous dichloromethane (2 mL) at 0° C. were successively added zinc iodide (14 mg, 0.04 mmol) and trimethylsilyl cyanide (64 μL, 0.51 mmol). The mixture was stirred at room temperature for 4 hours and then heated at 50° C. for 3 days. After cooling to room temperature, a saturated solution of sodium hydrogenocarbonate (5 mL) was added. Layers were separated and the aqueous layer was extracted with dichloromethane (2×6 mL). The organic layers were dried over sodium sulfate and concentrated in vacuo. The residue, dissolved in anhydrous methanol (3 mL) was added to a solution of acetyl chloride (0.36 mL, 5.13 mmol) in anhydrous methanol (2 mL), previously stirred 20 minutes at 0° C. under nitrogen atmosphere. The mixture was stirred at room temperature overnight. The solution was concentrated in vacuo and saturated solution of sodium hydrogenocarbonate (5 mL) was added to the residue. The aqueous layer was extracted with ethyl acetate (2×6 mL). The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by preparative TLC (dichloromethane/7M ammonia in methanol 97/3) to provide methyl 2-[4-(3,4-dihydro-2H-1-benzopyran-6-yl)-1-methyl-3-(pyridin-2-yl)-1H-pyrazol-5-yl]-2-hydroxyacetate (9g) (64 mg, 0.17 mmol, 39%).

1. customat 0° C.
2. temperatureheated at 50° C. for 3 days
3. temperatureAfter cooling to room temperature
4. customLayers were separated
5. extractionthe aqueous layer was extracted with dichloromethane (2×6 mL)
6. dry with materialThe organic layers were dried over sodium sulfate
7. concentrationconcentrated in vacuo
8. dissolutionThe residue, dissolved in anhydrous methanol (3 mL)
9. stirringThe mixture was stirred at room temperature overnight
10. concentrationThe solution was concentrated in vacuo and saturated solution of sodium hydrogenocarbonate (5 mL)
11. additionwas added to the residue
12. extractionThe aqueous layer was extracted with ethyl acetate (2×6 mL)
13. dry with materialThe organic layer was dried over sodium sulfate
14. concentrationconcentrated in vacuo
15. customThe residue was purified by preparative TLC (dichloromethane/7M ammonia in methanol 97/3)

ORD record

ord-ae6cbb1de216483b8b5658d769e5754b

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09260395B2