反応 #1973920

反応方程式

2,4,5-trichloropyrimidine

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

tri(isopropyl) borate

diisopropylamine

n-BuLi

→

title compound

収率 32.2%

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

収率 32.2%

溶媒

THF

THF

反応条件

後処理

1. 1
   workup.ADDITIONAfter the addition
2. 2
   温度cooled to −70° C
3. 3
   workup.STIRRINGThe reaction mixture is stirred at −70° C. for 30 min
4. 4
   温度The reaction is slowly warmed up to ambient temperature
5. 5
   workup.STIRRINGstirred for 1 h
6. 6
   その他The crude reaction mixture
7. 7
   その他is degassed
8. 8
   その他purged with N2 for three times
9. 9
   workup.STIRRINGstirred under nitrogen
10. 10
    温度at refluxing temperature for 1.5 h
11. 11
    その他The volatiles are removed in vacuo
12. 12
    抽出The residue is extracted with dichloromethane (DCM, 3×500 mL)
13. 13
    洗浄The combined extracts are washed with aqueous saturated sodium chloride (3×100 mL)
14. 14
    乾燥dried over anhydrous Na2SO4
15. 15
    ろ過filtered
16. 16
    濃縮concentrated
17. 17
    その他The residue is purified by chromatography on silica gel

実験手順

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].

出典