Sodium hydride → racemic N-{1-[5-(3-chlorophenyl)-1,2,4-oxadiazol-3-yl]ethyl}-5-(3,5-difluorophenyl)-N,4-dimethyl-4H-1,2,4-triazol-3-amine

HRID 732143Notes

Reaction equation

HRID 732143 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:9]2[N:10]([CH3:16])[C:11]([NH:14][CH3:15])=[N:12][N:13]=2)[CH:5]=[C:6]([F:8])[CH:7]=1.[H-].[Na+].CS(O[CH:24]([C:26]1[N:30]=[C:29]([C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([Cl:37])[CH:32]=2)[O:28][N:27]=1)[CH3:25])(=O)=O>CN(C=O)C.[NH4+].[Cl-]>[Cl:37][C:33]1[CH:32]=[C:31]([C:29]2[O:28][N:27]=[C:26]([CH:24]([N:14]([CH3:15])[C:11]3[N:10]([CH3:16])[C:9]([C:4]4[CH:5]=[C:6]([F:8])[CH:7]=[C:2]([F:1])[CH:3]=4)=[N:13][N:12]=3)[CH3:25])[N:30]=2)[CH:36]=[CH:35][CH:34]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 57837942[5-(3,5-Difluoro-phenyl)-4-methyl-4H-[1,2,4]triazol-3-yl]-methyl-amineHCID 578379891-[5-(3-Chlorophenyl)-[1,2,4]oxadiazol-3-yl]ethyl methanesulfonate

Product 1

HCID 11553762racemic N-{1-[5-(3-chlorophenyl)-1,2,4-oxadiazol-3-yl]ethyl}-5-(3,5-difluorophenyl)-N,4-dimethyl-4H-1,2,4-triazol-3-amineYield 44.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 25517Ammonium ChlorideSolvent

Procedure

To a solution of 5-(3,5-difluorophenyl)-N,4-dimethyl-4H-1,2,4-triazol-3-amine (0.47 g, 2.10 mmol) in DMF (10 ml) at r.t. under nitrogen was added NaH (77 mg, 3.20 mmol).After stirring for 15 min. a solution of 1-[5-(3-chlorophenyl)-1,2,4-oxadiazol-3-yl]ethyl methanesulfonate (0.70 g, 2.30 mmol) in DMF 10 ml was added. After 3 h the mixture was diluted with sat. NH4Cl solution and then extracted with EA. The organic phase was washed with H2O and brine, dried and evaporated. Purification by silica gel chromatography using hex.:EA=1:1 afforded 400 mg of the racemic N-{1-[5-(3-chlorophenyl)-1,2,4-oxadiazol-3-yl]ethyl}-5-(3,5-difluorophenyl)-N,4-dimethyl-4H-1,2,4-triazol-3-amine, which was separated using prep. chiral HPLC on a Chiralpak AD column (hex./2-propanol 80/20 to 100% 2-propanol) to give 183 mg (21%) of the title compound which eluted last. 1H NMR: 1.68 (d, 3 H) 2.89 (s, 3 H) 3.62 (s, 3 H) 4.79 (q, 1 H) 6.80-6.90 (m, 1 H) 7.19 (d, 2 H) 7.40 (t, 1 H) 7.49 (d, 1 H) 7.94 (d, 1 H) 8.04 (s, 1 H)

Workup

  1. additionwas added
  2. extractionextracted with EA
  3. washThe organic phase was washed with H2O and brine
  4. customdried
  5. customevaporated
  6. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-16e5d05021f14c81a0b0cfaf976f9e32
Source dataset
uspto-grants-2009_09
Patent number
US07585881B2

Reaction notes

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