반응 #1973920

반응 방정식

2,4,5-trichloropyrimidine

N-cyclopropyl-1-(ethoxymethyl)-1H-indole-4-carboxamide

tri(isopropyl) borate

diisopropylamine

n-BuLi

→

title compound

수율 32.2%

N-cyclopropyl-2-(2,5-dichloropyrimidin-4-yl)-1-(ethoxymethyl)-1H-indole-4-carboxamide

수율 32.2%

용매

THF

THF

반응 조건

후처리

1. 1
   workup.ADDITIONAfter the addition
2. 2
   온도cooled to −70° C
3. 3
   workup.STIRRINGThe reaction mixture is stirred at −70° C. for 30 min
4. 4
   온도The reaction is slowly warmed up to ambient temperature
5. 5
   workup.STIRRINGstirred for 1 h
6. 6
   기타The crude reaction mixture
7. 7
   기타is degassed
8. 8
   기타purged with N2 for three times
9. 9
   workup.STIRRINGstirred under nitrogen
10. 10
    온도at refluxing temperature for 1.5 h
11. 11
    기타The volatiles are removed in vacuo
12. 12
    추출The residue is extracted with dichloromethane (DCM, 3×500 mL)
13. 13
    세척The combined extracts are washed with aqueous saturated sodium chloride (3×100 mL)
14. 14
    건조dried over anhydrous Na2SO4
15. 15
    여과filtered
16. 16
    농축concentrated
17. 17
    기타The residue is purified by chromatography on silica gel

실험 절차

To a solution of diisopropylamine (DIPA, 147 mL, 1.04 mol) in anhydrous THF (600 mL) is added n-BuLi (2.5 M in hexane, 420 mL, 1.04 mol) at −50 C. After the addition, the mixture is stirred at −20° C. for 30 minutes and then cooled to −70° C. A solution of N-cyclopropyl-1-(ethoxymethyl)-1H-indole-4-carboxamide (60 g, 0.23 mol) and tri(isopropyl) borate (56.4 mL, 0.25 mol) in anhydrous THF (300 mL) is added. The reaction mixture is stirred at −70° C. for 30 min. The reaction is slowly warmed up to ambient temperature, stirred for 1 h and then quenched with aqueous K3PO4.3H2O (195 g, 0.74 mol, in 700 mL of water). The crude reaction mixture is degassed and purged with N2 for three times. 2,4,5-trichloropyrimidine (51 g, 0.27 mol) and palladium diphenylphosphinoferrocene dichloride (PdCl2(dppf).CH2Cl2, 19.2 g, 0.023 mol) are added and stirred under nitrogen at refluxing temperature for 1.5 h. The volatiles are removed in vacuo. The residue is extracted with dichloromethane (DCM, 3×500 mL). The combined extracts are washed with aqueous saturated sodium chloride (3×100 mL), dried over anhydrous Na2SO4, filtered and concentrated. The residue is purified by chromatography on silica gel to give the title compound (30 g, 32%). MS (m/z): 405 [(M+1)+, 35Cl, 35Cl], 407 [(M+1)+, 35Cl, 37Cl] and 409 [(M+1)+, 37Cl, 37Cl].

출처