Acetic Acid → 1-(4-Ethoxy-2,6-difluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]-pyrazole-3-carboximidamide

7.73 g of 1-(4-ethoxy-2,6-difluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]-pyrazole-3-carbonitrile 1-1-1 (25.5 mmol, 1.00 eq) were suspended in 100 mL methanol. 7.65 mL sodium methanolate in methanol (2.23 g, 41.3 mmol, 1.62 eq.) were added at rt. The reaction mixture was stirred for 4 h at rt. 2.36 mL acetic acid (2.45 g, 41.3 mmol, 1.62 eq.) and 2.05 g ammonium chloride (38.2 mmol, 1.50 eq.) were added and the reaction mixture was stirred at 50° C. for two days. The mixture was concentrated in vacuo and the residue was filtered off and washed with methanol. The filtrate was suspended in water and aqueous hydrochloric acid (4N). DCM was added, the aqueous layer was washed with DCM twice. To the aqueous layer aqueous sodiumhydroxid solution (2N) was added to reach pH 12. The aqueous layer was extracted with DCM/isopropanol (4:1) three times. The united organic layers were dried over a silicone filter, concentrated in vacuo to provide 2.67 g (7.99 mmol, 31.3%) of analytically pure target compound.

1. stirringthe reaction mixture was stirred at 50° C. for two days
2. concentrationThe mixture was concentrated in vacuo
3. filtrationthe residue was filtered off
4. washwashed with methanol
5. additionDCM was added
6. washthe aqueous layer was washed with DCM twice
7. additionTo the aqueous layer aqueous sodiumhydroxid solution (2N) was added
8. extractionThe aqueous layer was extracted with DCM/isopropanol (4:1) three times
9. dry with materialThe united organic layers were dried over a silicone
10. filtrationfilter
11. concentrationconcentrated in vacuo
12. customto provide 2.67 g (7.99 mmol, 31.3%) of analytically pure target compound

ORD record

ord-eb1608db11044b0f95acb59a26bd7c17

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09416125B2