1-(2-Amino-1,3-thiazol-5-yl)cyclobutan-1-ol → 5-Cyclobutyl-1,3-thiazol-2-amine

A solution of 1-(2-amino-thiazol-5-yl)cyclobutanol (Preparation 1; 6.6 g, 39 mmol) in trifluoroacetic acid (150 mL) was treated with 20% palladium hydroxide on carbon (2.3 g). The mixture was evacuated and purged with nitrogen (3 times), then was evacuated and purged with hydrogen gas (50 psi). The mixture was shaken for 24 hours and was evacuated and purged with nitrogen. The mixture was then filtered through Celite which was rinsed with methanol. The organic solvent was removed in vacuo, ethylacetate was added, followed by 29% ammonium hydroxide solution. The aqueous and organic layers were separated and the aqueous layer was extracted with ethylacetate. The combined organic layers were washed with brine, were dried (MgSO4), were filtered, and the solvent was removed in vacuo. The resulting residue was purified by silica gel chromatography (40:1:1 CHCl3—MeOH—NH4OH) to afford 4.75 g of 5-cyclobutyl-thiazol-2-ylamine, the title compound. 1HNMR (400 MHz, DMSO-d6): 6.66(s,2H), 6.57(s, 2H), 3.43 (m,1H), 2.20 (m,2H), 1.98-1.7 (m,4H).

1. customThe mixture was evacuated
2. custompurged with nitrogen (3 times)
3. customwas evacuated
4. custompurged with hydrogen gas (50 psi)
5. customwas evacuated
6. custompurged with nitrogen
7. filtrationThe mixture was then filtered through Celite which
8. washwas rinsed with methanol
9. customThe organic solvent was removed in vacuo, ethylacetate
10. additionwas added
11. customThe aqueous and organic layers were separated
12. extractionthe aqueous layer was extracted with ethylacetate
13. washThe combined organic layers were washed with brine
14. dry with materialwere dried (MgSO4)
15. filtrationwere filtered
16. customthe solvent was removed in vacuo
17. customThe resulting residue was purified by silica gel chromatography (40:1:1 CHCl3—MeOH—NH4OH)

ORD record

ord-1943e7c6151e4f8cb49a5227acd7e5d0

Source dataset

uspto-grants-2004_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06720427B2