反应详情

温度

80 °C

To a solution of cis-N-isopropyl-4-(2-nitro-5-(1H-1,2,4-triazol-1-yl)phenylamino)-cyclohexanecarboxamide (100 mg, 0.269 mmol) in EtOH (3 mL) was added tin(II) chloride dihydrate (242 mg, 1.074 mmol). The reaction was stirred at 80° C. After 3 hours, another four equivalents of tin(II) chloride dihydrate (242 mg, 1.074 mmol) was added, and the reaction was stirred at 80° C. for an additional 3 hours, and then at RT overnight. The reaction mixture was concentrated, and the residue was partitioned between EtOAc and 1 N aqueous sodium hydroxide. The aqueous layer was extracted with EtOAc; the combined organic layers were dried over anhydrous magnesium sulfate, filtered, and concentrated. The diamine was dissolved in THF (3 mL), cooled to 0° C., and 4-fluorobenzoyl isothiocyanate (53.5 mg, 0.296 mmol) was added. The reaction was stirred at 0° C. for 30 minutes, then DIPEA (0.070 mL, 0.403 mmol) and EDC (77 mg, 0.403 mmol) were added, and the reaction was stirred for 1 hour at 60° C. The residual material was concentrated, adsorbed onto a plug of silica gel, and purified by column chromatography, eluting with 20-100% EtOAc in DCM, to provide (E)-4-fluoro-N-(1-(cis-4-(isopropylcarbamoyl)cyclohexyl)-6-(1H-1,2,4-triazol-1-yl)-1H-benzo[d]imidazol-2(3H)-ylidene)benzamide as an off-white powder (44 mg, 33.5% yield). MS, m/z (C26H28FN7O2): Calc'd, 489.2. found, 489.9 [M+H].

1. stirringthe reaction was stirred at 80° C. for an additional 3 hours
2. customat RT
3. customovernight
4. concentrationThe reaction mixture was concentrated
5. customthe residue was partitioned between EtOAc and 1 N aqueous sodium hydroxide
6. extractionThe aqueous layer was extracted with EtOAc
7. dry with materialthe combined organic layers were dried over anhydrous magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. dissolutionThe diamine was dissolved in THF (3 mL)
11. temperaturecooled to 0° C.
12. stirringThe reaction was stirred at 0° C. for 30 minutes
13. stirringthe reaction was stirred for 1 hour at 60° C
14. concentrationThe residual material was concentrated
15. custompurified by column chromatography
16. washeluting with 20-100% EtOAc in DCM