Pyridine → HCID 87638157, compound

A solution of 2-aminothiazole (10.02 g, 100 mmol) and pyridine (8.3 mL, 103 mmol) in anhydrous acetonitrile (300 mL) was added to a thick suspension of N,N′-disuccinimidyl carbonate (26.13 g, 102 mmol) in acetonitrile (25 mL) with a small acetonitrile rinse. The mixture was stirred thoroughly for another 20 minutes, and then (R)-3-fluoropyrrolidine hydrochloride (13.06 g, 104 mmol) and diisopropylethylamine (70 mL, 402 mmol) were added and the reaction was stirred at room temperature overnight before being concentrated under vacuum. The residue was dissolved into ethyl acetate (100 mL), and then partitioned with hexanes (20 mL) and 3:1 water/brine (20 mL). The aqueous phase was separated and repeatedly back-extracted with 5:1 ethyl acetate/hexanes. The combined organic phases were washed with brine, and the aqueous phase was back-extracted with more 5:1 solution. The combined organic phases were then concentrated. The solids were dissolved into 6:1 dichloromethane/hexanes, mixed with 4:1 water/brine, and filtered through diatomaceous earth with a 6:1 dichloromethane/hexanes rinse. The filtrate was washed with more dilute brine, and the aqueous phase was separated and back-extracted with more 6:1 solution. This wash with dilute brine was repeated two more times. Then the organic phase was dried (sodium sulfate) and concentrated under vacuum to give the title compound.

1. washrinse
2. stirringthe reaction was stirred at room temperature overnight
3. concentrationbefore being concentrated under vacuum
4. dissolutionThe residue was dissolved into ethyl acetate (100 mL)
5. custompartitioned with hexanes (20 mL) and 3:1 water/brine (20 mL)
6. customThe aqueous phase was separated
7. extractionrepeatedly back-extracted with 5:1 ethyl acetate/hexanes
8. washThe combined organic phases were washed with brine
9. extractionthe aqueous phase was back-extracted with more 5:1 solution
10. concentrationThe combined organic phases were then concentrated
11. dissolutionThe solids were dissolved into 6:1 dichloromethane/hexanes
12. additionmixed with 4:1 water/brine
13. filtrationfiltered through diatomaceous earth with a 6:1 dichloromethane/hexanes
14. washrinse
15. washThe filtrate was washed with more dilute brine
16. customthe aqueous phase was separated
17. extractionback-extracted with more 6:1 solution
18. washThis wash with dilute brine
19. dry with materialThen the organic phase was dried (sodium sulfate)
20. concentrationconcentrated under vacuum

ORD record

ord-66e3e25e5502447689133442adcf1a33

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08383657B2