Sodium hydride → 5-n-Butyl-2,4-dihydro-4-[[2'-[N-(4-morpholinecarbonyl)sulfamoyl]biphenyl-4-yl]methyl]-2-[2-(trifluoromethyl)phenyl]-3H-1,2,4-triazol-3-one

HRID 36203

Reaction equation

HRID 36203 reaction equation
[CH2:1]([C:5]1[N:6]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[S:34](=[O:37])(=[O:36])[NH2:35])=[CH:24][CH:23]=2)[C:7](=[O:20])[N:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]([F:19])([F:18])[F:17])[N:9]=1)[CH2:2][CH2:3][CH3:4].[H-].[Na+].[N:40]1([C:46](Cl)=[O:47])[CH2:45][CH2:44][O:43][CH2:42][CH2:41]1>C1COCC1>[CH2:1]([C:5]1[N:6]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[S:34](=[O:37])(=[O:36])[NH:35][C:46]([N:40]3[CH2:45][CH2:44][O:43][CH2:42][CH2:41]3)=[O:47])=[CH:24][CH:23]=2)[C:7](=[O:20])[N:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]([F:19])([F:18])[F:17])[N:9]=1)[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 848104-Morpholinecarbonyl chlorideHCID 103469025-n-Butyl-2,4-dihydro-4-[(2'-sulfamoylbiphenyl-4-yl)methyl]-2-[2-(trifluoromethyl)phenyl]-3H-1,2,4-triazol-3-one

Product 1

HCID 199393685-n-Butyl-2,4-dihydro-4-[[2'-[N-(4-morpholinecarbonyl)sulfamoyl]biphenyl-4-yl]methyl]-2-[2-(trifluoromethyl)phenyl]-3H-1,2,4-triazol-3-oneYield 25.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 51.1 mg (0.0964 mmole) of 5-n-butyl-2,4-dihydro-4-[(2'-sulfamoylbiphenyl-4-yl)methyl]- 2-[2-(trifluoromethyl)phenyl]-3H-1,2,4-triazol-3-one (from Example 16, Step C) in 0.2 ml of dry THF was added 4.6 mg (0.116 mmole) of sodium hydride (60% in oil), and the mixture was allowed to stir at room temperature under N2 for 4 hours. Next, 17 μl (21.6 mg, 0.145 mmole) of 4-morpholinecarbonyl chloride was added, and the solution was stirred under N2 at room temperature overnight. The reaction was quenched by addition of 2 ml of H2O followed by extraction with 3×5 ml of ethyl acetate. The combined organic extracts were washed with 2×5 ml of H2O and then with 5 ml of brine. After co-evaporation twice from toluene, the crude product was flash chromatographed on silica gel (gradient elution with 0.3-10% MeOH in CH2Cl2) to give 16.1 mg of the title compound as a whitish glass; satisfactory purity by TLC in 19:1 and 9:1 CH2Cl2 --MeOH; mass spectrum (FAB) m/e 682 (M+K)+.

Workup

  1. stirringthe solution was stirred under N2 at room temperature overnight
  2. customThe reaction was quenched by addition of 2 ml of H2O
  3. extractionfollowed by extraction with 3×5 ml of ethyl acetate
  4. washThe combined organic extracts were washed with 2×5 ml of H2O
  5. customchromatographed on silica gel (gradient elution with 0.3-10% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-ba88eb7ccfd041bea5602986a6ac3ae8
Source dataset
uspto-grants-1995_05
Patent number
US05411980

Linked notes

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