Diisopropylethylamine → HCID 178522956, 화합물

({3-[(5-bromo-2-chloro-3-fluorophenyl)oxy]-4-chloro-2-fluorophenyl}methyl)amine (0.069 g, 0.181 mmol), 4-chloro-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxylic acid (0.050 g, 0.181 mmol) and DIPEA (0.063 mL, 0.361 mmol) were combined in THF (2 mL) and treated with HATU (0.076 g, 0.199 mmol) at 25° C. overnight with stirring. The reaction mixture was concentrated to dryness, dissolved in DCM, washed with water, dried over MgSO4, filtered and concentrated to dryness. The residue was dissolved in DCM (2.5 mL) and treated with TFA (2.5 mL) at 25° C. for 3 days. The reaction mixture was concentrated to dryness, dissolved in DCM, washed with saturated aqueous NaHCO3, dried over MgSO4, filtered and concentrated to dryness. The resultant solid was recrystallized from EtOH, cooled in an ice bath and filtered to give N-({3-[(5-bromo-2-chloro-3-fluorophenyl)oxy]-4-chloro-2-fluorophenyl}methyl)-4-chloro-1H-imidazole-5-carboxamide (0.048 g, 0.094 mmol, 51.9% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 13.17 (br. s., 1H), 8.27 (br. s., 1H), 7.78 (s, 1H), 7.63 (dd, J=8.52, 1.79 Hz, 1H), 7.53 (d, J=8.52 Hz, 1H), 7.39 (m, 1H), 6.76 (s, 1H), 4.54 (d, 2H). LC-MS (ES−) m/z 507.94, 509.95, 511.94 [M−1]. LC-MS (ES+) m/z 509.88, 511.87, 513.88 [M+H].

1. concentrationThe reaction mixture was concentrated to dryness
2. dissolutiondissolved in DCM
3. washwashed with water
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated to dryness
7. dissolutionThe residue was dissolved in DCM (2.5 mL)
8. additiontreated with TFA (2.5 mL) at 25° C. for 3 days
9. concentrationThe reaction mixture was concentrated to dryness
10. dissolutiondissolved in DCM
11. washwashed with saturated aqueous NaHCO3
12. dry with materialdried over MgSO4
13. filtrationfiltered
14. concentrationconcentrated to dryness
15. customThe resultant solid was recrystallized from EtOH
16. temperaturecooled in an ice bath
17. filtrationfiltered

ORD 기록

ord-5d7451a8528447ab905ec8f6b14d7f98

출처 데이터셋

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08304419B2