Reaction #64527

Reaction equation

sodium cyanoborohydride

THF

2-[4-amino-2-(trifluoromethyl)phenyl]-5-n-butyl-4-[[2'-[N-(2-chlorobenzoyl)sulfamoyl]biphenyl-4-yl]methyl]-2,4-dihydro-3H-1,2,4-triazol-3-one

2-[4-Amino-2-(trifluoromethyl)phenyl]-5-n-butyl-4-[[2'-[N-(2-chlorobenzoyl)sulfamoyl]biphenyl-4-yl]methyl]-2,4-dihydro-3H-1,2,4-triazol-3-one

benzaldehyde

piperidine

→

desired product

Yield 38.0%

2-[4-(Benzylamino)-2-(trifluoromethyl)phenyl]-5-n-butyl-4-[[2'-[N-(2-chlorobenzoyl)sulfamoyl]biphenyl-4-yl]methyl]-2,4-dihydro-3H-1,2,4-triazol-3-one

Yield 38.0%

Solvents

Water

isopropanol

Conditions

Workup

1. 1
   OtherThe crude material obtained
2. 2
   Temperatureafter cooling
3. 3
   Otherevaporation of volatiles
4. 4
   workup.DISSOLUTIONwas dissolved in 2.2 mL MeOH
5. 5
   workup.STIRRINGthe resulting mixture stirred at 0° C. for 2 hours
6. 6
   OtherAfter evaporation of volatiles
7. 7
   Otherchromatographed over silica gel (gradient elution with 0.5-5.0% MeOH/CH2Cl2)

Procedure

A solution of 70 mg (0.093 mmole) of 2-[4-amino-2-(trifluoromethyl)phenyl]-5-n-butyl-4-[[2'-[N-(2-chlorobenzoyl)sulfamoyl]biphenyl-4-yl]methyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (from Example 56), 33 mg (0.31 mmole) of benzaldehyde, 2.1 mL of piperidine, and 2.5 mL of isopropanol was stirred at 95° C. overnight. The crude material obtained after cooling and evaporation of volatiles was dissolved in 2.2 mL MeOH, charged with 1.3 mL of a 1M solution of sodium cyanoborohydride in THF (1.3 mmole), and stirred at room temperature for 2 hours. Water (160 mL) was added at 0° C., and the resulting mixture stirred at 0° C. for 2 hours. After evaporation of volatiles, the crude product was flash chromatographed over silica gel (gradient elution with 0.5-5.0% MeOH/CH2Cl2) to afford 27 mg (38%) of the desired product as a cream-colored solid, mp >107° C. (gradual), homogeneous by TLC (9:1MeOH/CH2Cl2), mass spectrum (FAB) m/e 774 (M+1)+.

Source