반응 #159081

반응 방정식

(1-{2-[5-(7-bromo-9,10-dihydro-phenanthren-2-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester

tributyl(1-ethoxyvinyl)tin

NBS

2-aza-bicyclo[2.2.1]heptane-2,3-dicarboxylic acid 2-tert-butyl ester

DIPEA

→

2-Aza-bicyclo[2.2.1]heptane-2,3-dicarboxylic acid 2-tert-butyl ester 3-[2-(7-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-9,10-dihydro-phenanthren-2-yl)-2-oxo-ethyl]ester

용매

ethyl acetate

dioxane

Water

ethyl acetate

acetonitrile

반응 조건

후처리

1. 1
   기타The reaction mixture was flushed with nitrogen
2. 2
   온도cooled to ambient temperature
3. 3
   세척Washed with water and brine
4. 4
   건조dried over Na2SO4
5. 5
   여과filtered
6. 6
   농축concentrated in vacuo
7. 7
   workup.DISSOLUTIONThe obtained residue was dissolved in acetonitrile (3 mL)
8. 8
   workup.STIRRINGThe mixture was stirred at room temperature for 16 hours
9. 9
   세척The organic layer was washed with NaHCO3 solution and water
10. 10
    건조dried over Na2SO4
11. 11
    여과filtered
12. 12
    농축concentrated in vacuo
13. 13
    기타The obtained residue was purified by flash chromatography

실험 절차

Pd(Ph3)4 (15 mg, 0.015 mmol) and PdCl2(Ph3)2 (10 mg, 0.015 mmol) were added to a mixture of (1-{2-[5-(7-bromo-9,10-dihydro-phenanthren-2-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (200 mg, 0.37 mmol) and tributyl(1-ethoxyvinyl)tin (0.15 mL, 0.44 mL) in 5 mL dioxane. The reaction mixture was flushed with nitrogen, heated at 80° C. for 16 hours, then cooled to ambient temperature. Water (1.5 mL) and NBS (78 mg, 0.44 mmol) was added and the mixture was stirred at room temperature for 40 minutes, then diluted with ethyl acetate (100 mL). Washed with water and brine, dried over Na2SO4, filtered and concentrated in vacuo. The obtained residue was dissolved in acetonitrile (3 mL). To it was added a solution of 2-aza-bicyclo[2.2.1]heptane-2,3-dicarboxylic acid 2-tert-butyl ester (167 mg, 0.69 mmol) and DIPEA (0.11 mL, 0.67 mmol) in 2 mL acetonitrile. The mixture was stirred at room temperature for 16 hours, then diluted with ethyl acetate (100 mL). The organic layer was washed with NaHCO3 solution and water, dried over Na2SO4, filtered and concentrated in vacuo. The obtained residue was purified by flash chromatography to provide the desired product 2-Aza-bicyclo[2.2.1]heptane-2,3-dicarboxylic acid 2-tert-butyl ester 3-[2-(7-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-9,10-dihydro-phenanthren-2-yl)-2-oxo-ethyl]ester as a brown oil (130 mg, 47% over two steps). m/z 754.3 (M+H)+.

출처