Water → HCID 90092931, compound

Under a nitrogen atmosphere, sodium borohydride (0.51 g, 13.60 mmol) was added portionwise to a solution of 3-(thiophen-2-yl)-1H-pyrazole-5-carbaldehyde (34b) (2.02 g, 11.33 mmol) in anhydrous methanol (80 mL). The reaction mixture was stirred at room temperature for 4 hours. Water was added (50 mL) and the mixture was concentrated in vacuo. The residue was dissolved in ethyl acetate (40 mL) and successively washed with water (40 mL) and brine (40 mL). The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was dissolved in acetonitrile (100 mL) and N-bromosuccinimide (1.35 g, 7.59 mmol) was added. The mixture was stirred for 60 minutes at room temperature, then concentrated in vacuo. The residue was dissolved in ethyl acetate (40 mL) and washed with brine (40 mL). The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was dissolved in a mixture of chloroform (14 mL) and N,N-dimethylformamide (28 mL). Manganese dioxide (3.74 g, 43.02 mmol) was added and the mixture was stirred at 50° C. for 1 hour. The mixture was filtered through a pad of Celite®, rinced with N,N-dimethylformamide, the filtrate was concentrated in vacuo, and co-evaporated with toluene. The residue was triturated with diethyl ether and filtered to provide 4-bromo-3-(thiophen-2-yl)-1H-pyrazole-5-carbaldehyde (34c) (1.07 g, 4.16 mmol, 37%).

1. concentrationthe mixture was concentrated in vacuo
2. dissolutionThe residue was dissolved in ethyl acetate (40 mL)
3. washsuccessively washed with water (40 mL) and brine (40 mL)
4. dry with materialThe organic layer was dried over sodium sulfate
5. concentrationconcentrated in vacuo
6. dissolutionThe residue was dissolved in acetonitrile (100 mL)
7. stirringThe mixture was stirred for 60 minutes at room temperature
8. concentrationconcentrated in vacuo
9. dissolutionThe residue was dissolved in ethyl acetate (40 mL)
10. washwashed with brine (40 mL)
11. dry with materialThe organic layer was dried over sodium sulfate
12. concentrationconcentrated in vacuo
13. dissolutionThe residue was dissolved in a mixture of chloroform (14 mL) and N,N-dimethylformamide (28 mL)
14. stirringthe mixture was stirred at 50° C. for 1 hour
15. filtrationThe mixture was filtered through a pad of Celite®
16. concentrationthe filtrate was concentrated in vacuo
17. customThe residue was triturated with diethyl ether
18. filtrationfiltered

ORD record

ord-4522d5b6e199401ea588746214387fb4

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09260395B2