1,2-Dichloroethane → N-{2-[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]ethyl}-3-({[(4-methoxy-2,6-dimethylphenyl)sulfonyl](methyl)amino}methyl)-1,2,4-oxadiazole-5-carboxamide

HRID 469031Notes

Reaction equation

HRID 469031 reaction equation
[NH:1]1[CH2:5][CH2:4][N:3]=[C:2]1[C:6]1[CH:11]=[CH:10][C:9]([CH2:12][CH2:13][NH2:14])=[CH:8][CH:7]=1.C[Al](C)C.[CH3:19][O:20][C:21]1[CH:26]=[C:25]([CH3:27])[C:24]([S:28]([N:31]([CH2:33][C:34]2[N:38]=[C:37]([C:39](OCC)=[O:40])[O:36][N:35]=2)[CH3:32])(=[O:30])=[O:29])=[C:23]([CH3:44])[CH:22]=1.ClCCCl>C(Cl)Cl>[NH:3]1[CH2:4][CH2:5][N:1]=[C:2]1[C:6]1[CH:7]=[CH:8][C:9]([CH2:12][CH2:13][NH:14][C:39]([C:37]2[O:36][N:35]=[C:34]([CH2:33][N:31]([S:28]([C:24]3[C:23]([CH3:44])=[CH:22][C:21]([O:20][CH3:19])=[CH:26][C:25]=3[CH3:27])(=[O:30])=[O:29])[CH3:32])[N:38]=2)=[O:40])=[CH:10][CH:11]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 16682925TrimethylaluminumHCID 223907052-[4-(4,5-Dihydro-1H-imidazol-2-yl)phenyl]ethan-1-amineHCID 58393145Ethyl 3-({[(4-methoxy-2,6-dimethylphenyl)sulfonyl] (methyl)amino}methyl)-1,2,4-oxadiazole-5-carboxylate

Product 1

HCID 58393084N-{2-[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]ethyl}-3-({[(4-methoxy-2,6-dimethylphenyl)sulfonyl](methyl)amino}methyl)-1,2,4-oxadiazole-5-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 2-[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]ethanamine (bis TFA salt, 108 mg, 0.26 mmol) in DCM (3 mL) at 0° C. was added trimethyl aluminium (2 M in toluene, 0.13 mL, 0.26 mmol) and the mixture was stirred at 0° C. for 15 min. Ethyl 3-({[(4-methoxy-2,6-dimethylphenyl)sulfonyl](methyl)amino}methyl)-1,2,4-oxadiazole-5-carboxylate (50 mg, 0.13 mmol) was added dropwise as a solution in DCM (2 mL), followed by TEA (0.045 mL, 0.32 mmol). The reaction was stirred at ambient temperature for 18 h, after which time TEA (0.110 mL, 0.79 mmol) and DCE (4 mL) were added. The reaction was heated to 60° C. for 18 h, then partitioned between saturated aqueous NH4Cl (20 mL) and EtOAc (2×20 mL). The aqueous layer was extracted with DCM (2×10 mL) and these extracts were dried over MgSO4 and solvents were removed in vacuo. A portion of the product was purified using prep method A.

Workup

  1. stirringThe reaction was stirred at ambient temperature for 18 h
  2. temperatureThe reaction was heated to 60° C. for 18 h
  3. custompartitioned between saturated aqueous NH4Cl (20 mL) and EtOAc (2×20 mL)
  4. extractionThe aqueous layer was extracted with DCM (2×10 mL)
  5. dry with materialthese extracts were dried over MgSO4 and solvents
  6. customwere removed in vacuo
  7. customA portion of the product was purified

Sources & evidence

ORD record
ord-ecef3fe7f1ae43e69334b9de18d218a1
Source dataset
uspto-grants-2014_01
Patent number
US08623859B2

Reaction notes

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