Benzaldehyde → 4''-[1-(4-Benzylamino-2-trifluoromethyl-phenyl)-3-butyl-5-oxo-1,5-dihydro-[1,2,4]triazol-4-ylmethyl]-biphenyl-2-sulfonic acid 2-chloro-benzoylamide

HRID 36249Notes

Reaction equation

HRID 36249 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12](=[O:13])[N:11]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[S:27](=[O:39])(=[O:38])[NH:28][C:29](=[O:37])[C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=4[Cl:36])=[CH:17][CH:16]=3)[C:10]([CH2:40][CH2:41][CH2:42][CH3:43])=[N:9]2)=[C:4]([C:44]([F:47])([F:46])[F:45])[CH:3]=1.[CH:48](=O)[C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1.N1CCCCC1.C([BH3-])#N.[Na+].C1COCC1>O.C(O)(C)C>[CH2:48]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12](=[O:13])[N:11]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[S:27](=[O:38])(=[O:39])[NH:28][C:29](=[O:37])[C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=4[Cl:36])=[CH:17][CH:16]=3)[C:10]([CH2:40][CH2:41][CH2:42][CH3:43])=[N:9]2)=[C:4]([C:44]([F:46])([F:45])[F:47])[CH:3]=1)[C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1

Participants

8

Reactant 5

HCID 240BenzaldehydeHCID 8028TetrahydrofuranHCID 8082PiperidineHCID 5003444Sodium cyanoborohydrideHCID 103948294''-[1-(4-Amino-2-trifluoromethyl-phenyl)-3-butyl-5-oxo-1,5-dihydro-[1,2,4]triazol-4-ylmethyl]-biphenyl-2-sulfonic acid 2-chloro-benzoylamide

Product 1

HCID 104402034''-[1-(4-Benzylamino-2-trifluoromethyl-phenyl)-3-butyl-5-oxo-1,5-dihydro-[1,2,4]triazol-4-ylmethyl]-biphenyl-2-sulfonic acid 2-chloro-benzoylamideYield 38%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent

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)+.

Workup

  1. customThe crude material obtained
  2. temperatureafter cooling
  3. customevaporation of volatiles
  4. dissolutionwas dissolved in 2.2 mL MeOH
  5. stirringthe resulting mixture stirred at 0° C. for 2 hours
  6. customAfter evaporation of volatiles
  7. customchromatographed over silica gel (gradient elution with 0.5-5.0% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-a6309a499853475b8e93b3229f06d98a
Source dataset
uspto-grants-1995_05
Patent number
US05411980

Reaction notes

Loading…