4'-Hydroxyacetophenone → HCID 67549566, compound

A mixture of methyl bromoacetate (690 μL, 7.3 mmol) and 4-hydroxyacetophenone (1 g, 7.3 mmol) was dissolved in acetone (100 mL), followed by addition of anhydrous K2CO3 (10 g, 73 mmol). The reaction mixture was stirred at room temperature overnight, filtered, and the filtrate was concentrated in vacuo. The resulting residue was dissolved in dioxane (21 mL), and a portion of the obtained solution (3.2 mL, 1.03 mmol) was combined with a solution of NaOH (64 mg, 1.6 mmol) in water (3 mL). The reaction mixture was maintained at room temperature for 1 h, then concentrated in vacuo. The residue was dissolved in water (3 mL) and neutralized with 1M HCl. The mixture was extracted with EtOAc (10 mL), and the organic layer was dried over MgSO4 and concentrated in vacuo. The crude acid was dissolved in THF (36 mL) and a portion of the obtained solution (5.2 mL, 0.14 mmol) was combined with phenyltrimethylammonium tribromide (93 mg, 0.14 mmol). The reaction mixture was heated at reflux for 1 h, cooled and stirred at room temperature overnight, then concentrated in vacuo. The resulting residue was dissolved in water (15 mL) and extracted with dichloromethane (2×30 mL). The combined organic extracts were dried over MgSO4 and concentrated in vacuo. The crude bromoketone was dissolved in dry dioxane (1 mL) followed by the addition of (3-morpholin-4-yl-propyl)-thiourea (28 mg, 0.14 mmol). The reaction mixture was heated at 80° C. for 1 h, cooled to room temperature, then concentrated in vacuo. The resulting crude aminothiazole was suspended in dry chloroform (600 μL) followed by addition of N,N-diisopropylethylamine (52 μL, 0.3 mmol) and thiophene-2-carbonyl chloride (24 μL, 0.22 mmol). The reaction mixture was stirred at room temperature for 30 min, then concentrated in vacuo. The resulting residue was dissolved in AcOH/water (1:1, 5 mL), heated at reflux for 30 min, cooled to room temperature, then concentrated in vacuo. The resulting crude product was dissolved in DMSO (800 μL) and a portion of the obtained solution (200 μL, 0.035 mmol) was subjected to HPLC purification (Method Z) to provide the title compound (2.4 mg) as a colorless amorphous solid. LC/MS (ESI) m/z 488.3 [M+H]. HPLC retention time (Method B)=2.58 min.

1. filtrationfiltered
2. concentrationthe filtrate was concentrated in vacuo
3. dissolutionThe resulting residue was dissolved in dioxane (21 mL)
4. temperatureThe reaction mixture was maintained at room temperature for 1 h
5. concentrationconcentrated in vacuo
6. dissolutionThe residue was dissolved in water (3 mL)
7. extractionThe mixture was extracted with EtOAc (10 mL)
8. dry with materialthe organic layer was dried over MgSO4
9. concentrationconcentrated in vacuo
10. dissolutionThe crude acid was dissolved in THF (36 mL)
11. temperatureThe reaction mixture was heated
12. temperatureat reflux for 1 h
13. temperaturecooled
14. stirringstirred at room temperature overnight
15. concentrationconcentrated in vacuo
16. dissolutionThe resulting residue was dissolved in water (15 mL)
17. extractionextracted with dichloromethane (2×30 mL)
18. dry with materialThe combined organic extracts were dried over MgSO4
19. concentrationconcentrated in vacuo
20. dissolutionThe crude bromoketone was dissolved in dry dioxane (1 mL)
21. temperatureThe reaction mixture was heated at 80° C. for 1 h
22. temperaturecooled to room temperature
23. concentrationconcentrated in vacuo
24. stirringThe reaction mixture was stirred at room temperature for 30 min
25. concentrationconcentrated in vacuo
26. dissolutionThe resulting residue was dissolved in AcOH/water (1:1, 5 mL)
27. temperatureheated
28. temperatureat reflux for 30 min
29. temperaturecooled to room temperature
30. concentrationconcentrated in vacuo
31. dissolutionThe resulting crude product was dissolved in DMSO (800 μL)

ORD record

ord-a8d1af5dc84e4168ac5ced160b662277

Source dataset

uspto-grants-2008_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07410988B2