Sodium Bicarbonate → HCID 22473967, compound

A mixture of 3-(benzo[b]thiophen-4-yl)-2-methyl-5,6-dihydroimidazo[2,1-b]thiazole hydrochloride (2 g; prepared in a manner similar to that described in Example 9 Method A), 5M aqueous sodium hydrogencarbonate solution (50 ml) and dichloromethane (50 ml) was stirred at ambient temperature for 30 minutes, then the free base was extracted into dichloromethane (2×50 ml). The combined extracts were dried (MgSO4) and the solvent was removed in vacuo. The residue was dissolved in tetrahydrofuran (40 ml), then the stirred solution was cooled to −70° C. and n-butyllithium (2.5M solution in hexanes; 2.85 ml) was added dropwise under nitrogen. The mixture was stirred at −70° C. for 1 hour, then methyl iodide (0.45 ml) was added dropwise. The mixture was stirred at −70° C. for 1 hour then it was poured into saturated aqueous ammonium chloride solution (50 ml). The product was extracted into ethyl acetate (2×50 ml), the combined extracts were dried (MgSO4) and the solvents were removed in vacuo. The residue was purified via flash chromatography over silica using a 9:1 mixture of dichloromethane and methanol as eluant. Appropriate fractions were combined and the solvents were removed in vacuo. The residue was dissolved in ethanol, concentrated hydrochloric acid (10 drops) was added, the solvent was removed in vacuo, and the residue was triturated with ether (30 ml). The mixture was allowed to stand at ambient temperature for 72 hours then the resulting solid was collected by filtration and dried in vacuo to give 2-methyl-3-(2-methylbenzo[b]thiophen-4-yl)-5,6-dihydroimidazo[2,1-b]thiazole hydrochloride (1.15 g) as a colourless solid, m.p. 271° C.

1. customprepared in a manner similar to
2. extractionthe free base was extracted into dichloromethane (2×50 ml)
3. dry with materialThe combined extracts were dried (MgSO4)
4. customthe solvent was removed in vacuo
5. dissolutionThe residue was dissolved in tetrahydrofuran (40 ml)
6. temperaturethe stirred solution was cooled to −70° C.
7. additionn-butyllithium (2.5M solution in hexanes; 2.85 ml) was added dropwise under nitrogen
8. stirringThe mixture was stirred at −70° C. for 1 hour
9. additionmethyl iodide (0.45 ml) was added dropwise
10. stirringThe mixture was stirred at −70° C. for 1 hour
11. additionit was poured into saturated aqueous ammonium chloride solution (50 ml)
12. extractionThe product was extracted into ethyl acetate (2×50 ml)
13. dry with materialthe combined extracts were dried (MgSO4)
14. customthe solvents were removed in vacuo
15. customThe residue was purified via flash chromatography over silica using
16. additiona 9:1 mixture of dichloromethane and methanol as eluant
17. customthe solvents were removed in vacuo
18. dissolutionThe residue was dissolved in ethanol
19. additionconcentrated hydrochloric acid (10 drops) was added
20. customthe solvent was removed in vacuo
21. customthe residue was triturated with ether (30 ml)
22. waitto stand at ambient temperature for 72 hours
23. filtrationthe resulting solid was collected by filtration
24. customdried in vacuo

ORD record

ord-6805a904446d44a9a7863e69a0f5f354

Source dataset

uspto-grants-2005_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06900216B2