反应详情

A suspension of cis-4-((E)-6-((4-((tert-butoxycarbonylamino)methyl)piperidin-1-yl)methyl)-2-(4-fluorobenzoylimino)-2,3-dihydro-1H-benzo[d]imidazol-1-yl)cyclohexanecarboxylic acid (0.57 g, 0.94 mmol) in thionyl chloride (6.85 mL, 94 mmol) under nitrogen atmosphere was stirred for 30 minutes at RT and then concentrated to dryness. The residue was suspended in THF (9.4 mL) and cooled in an ice bath under nitrogen atmosphere. To the resulting mixture was added isopropylamine (0.804 mL, 9.38 mmol) as a solution in THF (1 mL). The ice bath was removed and the mixture was stirred for 1 hour at RT. The resulting mixture was diluted with water (10 mL) and the aqueous layer extracted with DCM (30 mL). The organic layer was dried over sodium sulfate and concentrated to dryness under high vacuum to afford a tan solid. The solid was suspended in HCl (4.0M in dioxanes) (23.45 mL, 94 mmol) and stirred for 16 hours. The mixture was concentrated, suspended in DCM and washed with aqueous NaHCO3 solution. The organic portion was collected, dried over sodium sulfate, and concentrated to dryness under high vacuum to afford a tan solid. The solid was purified by silica gel chromatography (1-10% MeOH/DCM (1% NH4OH)) to afford (E)-N-(6-((4-(aminomethyl)piperidin-1-yl)methyl)-1-(cis-4-(isopropylcarbamoyl)cyclohexyl)-1H-benzo[d]imidazol-2(3H)-ylidene)-4-fluorobenzamide (0.3 g, 58.3% yield). MS m/z=549.2 [M+H]. Calc'd for C31H41FN6O2: 548.3.

1. concentrationconcentrated to dryness
2. temperaturecooled in an ice bath under nitrogen atmosphere
3. customThe ice bath was removed
4. stirringthe mixture was stirred for 1 hour at RT
5. additionThe resulting mixture was diluted with water (10 mL)
6. extractionthe aqueous layer extracted with DCM (30 mL)
7. dry with materialThe organic layer was dried over sodium sulfate
8. concentrationconcentrated to dryness under high vacuum
9. customto afford a tan solid
10. stirringstirred for 16 hours
11. concentrationThe mixture was concentrated
12. washwashed with aqueous NaHCO3 solution
13. customThe organic portion was collected
14. dry with materialdried over sodium sulfate
15. concentrationconcentrated to dryness under high vacuum
16. customto afford a tan solid
17. customThe solid was purified by silica gel chromatography (1-10% MeOH/DCM (1% NH4OH))