Methanol → HCID 90092585, compound

Under nitrogen atmosphere, to a solution of 1-methyl-4-(5-methyl-3,4-dihydro-2H-1-benzopyran-6-yl)-3-(thiophen-2-yl)-1H-pyrazole-5-carbaldehyde (7h) (103 mg, 0.30 mmol) in anhydrous dichloromethane (2 mL) at 0° C. were successively added zinc iodide (10 mg, 0.03 mmol) and trimethylsilyl cyanide (46 μL, 0.37 mmol). The mixture was stirred at room temperature for 88 hours then heated at 40° C. for 4 hours. 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 (1 mL), was added to a solution of acetyl chloride (0.26 mL, 3.65 mmol) in anhydrous methanol (2 mL), previously stirred for 20 minutes at 0° C. under nitrogen atmosphere. The mixture was stirred at room temperature overnight. The solution was concentrated in vacuo and a 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/ethyl acetate 80/20) to provide methyl 2-hydroxy-2-[1-methyl-4-(5-methyl-3,4-dihydro-2H-1-benzopyran-6-yl)-3-(thiophen-2-yl)-1H-pyrazol-5-yl]acetate (7i) (79 mg, 0.20 mmol, 65%).

1. customat 0° C.
2. temperaturethen heated at 40° C. for 4 hours
3. customLayers were separated
4. extractionthe aqueous layer was extracted with dichloromethane (2×6 mL)
5. dry with materialThe organic layers were dried over sodium sulfate
6. concentrationconcentrated in vacuo
7. dissolutionThe residue, dissolved in anhydrous methanol (1 mL)
8. stirringpreviously stirred for 20 minutes at 0° C. under nitrogen atmosphere
9. stirringThe mixture was stirred at room temperature overnight
10. concentrationThe solution was concentrated in vacuo
11. additiona saturated solution of sodium hydrogenocarbonate (5 mL) was 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/ethyl acetate 80/20)

ORD record

ord-6322431a97794671b6b9e9fe1b3e2738

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09260395B2