Imidazole → HCID 178474530, compound

To a stirred solution of the 2-(1-trityl-1H-imidazol-4-yl)phenol (0.5 mmol) in anhydrous DMF (3 mL) at 0° C. was added NaH (36.0 mg, 0.75 mmol). The resulting suspension was allowed to stir for 10 min. To the resulting solution was added 3-(acetamidomethyl)benzyl 4-methylbenzenesulfonate (200.0 mg, 0.6 mmol). After stirring overnight, the reaction mixture was carefully diluted with water and extracted with ethyl acetate (2×10 mL). The combined organic layers were washed with water, brine and dried (Na2SO4). The solvent was removed under reduced pressure and the crude product purified using column chromatography. The product was isolated as white solid in 63% yield. 1H NMR:1.95 (s, 3H), 4.21 (d, 2H, J=6.0 Hz), 4.95 (s, 2H), 5.65 (bis, 1H), 6.91 (d, 1H, J=7.6 Hz), 7.10-7.30 (m, 21H), 7.40-7.46 (m, 3H), 7.60-7.68 (m, 1H), 8.19 (dd, 1H, J=7.6, 1.6 Hz). To a stirred solution of the obtained imidazole (0.25 mmol) in anhydrous DMF (3 mL) at 0° C. was added NaH (18.0 mg, 0.37 mmol). The resulting suspension was allowed to stir for 10 min. To the resulting solution was added benzylbromide (51.0 mg, 0.30 mmol). After stirring overnight, the reaction mixture was carefully diluted with water and extracted with ethyl acetate (2×10 mL). The combined organic layers were washed with water, brine and dried (Na2SO4). The solvent was removed under reduced pressure and the crude product was taken to next step without further purification. To a solution of the crude product obtained above was added acetic acid (1.0 mL) and MeOH (4.0 mL). The solution was stirred at 80° C. for 2 h. The solution was allowed to cool to room temperature and the pH was adjusted to ˜10 with 10% NaOH (aq). The aqueous phase was extracted with EtOAc (3×20 mL). The combined organic layer were washed with water, brine, and dried. The solvent was removed in vacuum to afford the crude residue, which was purified by flash column chromatography on silica gel to afford the desired product (1:1 rotamer) in 35% overall yield. 1H NMR:2.15 (s, 3H), 2.18 (s, 3H), 4.18 (s, 2H), 4.47 (s, 2H), 4.60 (s, 2H), 5.15 (s, 2H), 5.18 (s, 2H), 7.00-7.50 (m, 22H), 7.56 (s, 2H), 7.66 (s, 2H), 7.93 (d, 2H, J=7.6 Hz), 8.07 (d, 2H, J=7.6 Hz)

1. stirringAfter stirring overnight
2. extractionextracted with ethyl acetate (2×10 mL)
3. washThe combined organic layers were washed with water, brine
4. dry with materialdried (Na2SO4)
5. customThe solvent was removed under reduced pressure
6. customthe crude product purified
7. customThe product was isolated as white solid in 63% yield
8. stirringto stir for 10 min
9. stirringAfter stirring overnight
10. extractionextracted with ethyl acetate (2×10 mL)
11. washThe combined organic layers were washed with water, brine
12. dry with materialdried (Na2SO4)
13. customThe solvent was removed under reduced pressure
14. customthe crude product was taken to next step without further purification
15. customTo a solution of the crude product obtained
16. stirringThe solution was stirred at 80° C. for 2 h
17. extractionThe aqueous phase was extracted with EtOAc (3×20 mL)
18. washThe combined organic layer were washed with water, brine
19. customdried
20. customThe solvent was removed in vacuum
21. customto afford the crude residue, which
22. customwas purified by flash column chromatography on silica gel

ORD record

ord-26095e6295c149c8bb38e6d9c16dc8c5

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08722720B2