Reaction #49825

Reaction equation

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

Yield 45.2%

Solvents

triethylamine

acetonitrile

Conditions

Workup

1. 1
   workup.STIRRINGunder stirring at room temperature for 4 hours
2. 2
   FiltrationThe precipitate is filtered
3. 3
   Washwashed with acetonitrile
4. 4
   ConcentrationThe 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
   Washwashed with water
8. 8
   workup.DISSOLUTIONdissolved in chloroform
9. 9
   Washwashed with 1N HCl
10. 10
    OtherThe organic solution is evaporated in vacuo to dryness
11. 11
    Otherthe residue is purified over a SiO2 column
12. 12
    OtherFinal crystallization from CH2Cl 2 /ethyl acetate

Procedure

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.

Source