Reaktion #49825

Reaktionsgleichung

dimethylaminoethanol

Glycine methyl ester hydrochloride

3-(7-carboxy-1,4-dihydro-1-phenyl-indeno[1,2-c]pyrazole-3-yl)-2-cyano-3-oxo-N-phenyl-propanamide

dicyclohexylcarbodiimide

→

N-[1,4-dihydro-1-phenyl-3-(2-phenylcarbamoyl-cyano-acetyl)indeno[1,2-c]pyrazol-7-yl] carbonyl-glycine methyl ester

Ausbeute 45.2%

Lösungsmittel

triethylamine

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGunder stirring at room temperature for 4 hours
2. 2
   FiltrationThe precipitate is filtered
3. 3
   Waschenwashed with acetonitrile
4. 4
   EinengenThe organic solution is concentrated in vacuo to a small volume
5. 5
   workup.ADDITIONdiluted with water
6. 6
   FiltrationThe obtained precipitate is filtered
7. 7
   Waschenwashed with water
8. 8
   workup.DISSOLUTIONdissolved in chloroform
9. 9
   Waschenwashed with 1N HCl
10. 10
    SonstigeThe organic solution is evaporated in vacuo to dryness
11. 11
    Sonstigethe residue is purified over a SiO2 column
12. 12
    SonstigeFinal crystallization from CH2Cl 2 /ethyl acetate

Vorschrift

Glycine methyl ester hydrochloride (0.7 g) suspended in anhydrous acetonitrile (250 ml) is treated with triethylamine (0.56 g) under stirring at room temperature. To the suspension first 3-(7-carboxy-1,4-dihydro-1-phenyl-indeno[1,2-c]pyrazole-3-yl)-2-cyano-3-oxo-N-phenyl-propanamide (2.3 g) and the dicyclohexylcarbodiimide (1.25 g) are added. The reaction mixture is kept under stirring at room temperature for 4 hours and then is basified to pH 8 by adding dimethylaminoethanol. The precipitate is filtered, washed with acetonitrile and then eliminated. The organic solution is concentrated in vacuo to a small volume, diluted with water, acidified to pH 2 with 1N HCl and then basified to pH 8 with 1N NaOH. The obtained precipitate is filtered, washed with water, dissolved in chloroform and washed with 1N HCl and then with water until neutral. The organic solution is evaporated in vacuo to dryness and the residue is purified over a SiO2 column using CHCl3 /methanol 90/10 as eluent. Final crystallization from CH2Cl 2 /ethyl acetate yields 1.2 g of pure N-[1,4-dihydro-1-phenyl-3-(2-phenylcarbamoyl-cyano-acetyl)indeno[1,2-c]pyrazol-7-yl] carbonyl-glycine methyl ester.

Quelle