1,2-Dichloroethane → 3-{3,5-Dimethyl-4-[6-(5-o-tolyl-[1,3,4]oxadiazol-2-yl)-1H-benzoimidazol-2-yl]-phenyl}-2,2-dimethyl-propionic acid

HRID 1513296Notes

Reaction equation

HRID 1513296 reaction equation
C[O:2][C:3](=[O:37])[C:4]([CH3:36])([CH3:35])[CH2:5][C:6]1[CH:11]=[C:10]([CH3:12])[C:9]([C:13]2[NH:17][C:16]3[CH:18]=[C:19]([C:22]4[O:23][C:24]([C:27]5[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=5[CH3:33])=[N:25][N:26]=4)[CH:20]=[CH:21][C:15]=3[N:14]=2)=[C:8]([CH3:34])[CH:7]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.COC(C(C)(C)CC1C=C(C)C(C2NC3C=C(C(O)=O)C=CC=3N=2)=C(C)C=1)=O.CC1C=CC=CC=1C(NN)=O.CC[N+](S(N=C(OC)[O-])(=O)=O)(CC)CC>CN(C=O)C.CCOC(C)=O>[CH3:12][C:10]1[CH:11]=[C:6]([CH2:5][C:4]([CH3:36])([CH3:35])[C:3]([OH:37])=[O:2])[CH:7]=[C:8]([CH3:34])[C:9]=1[C:13]1[NH:17][C:16]2[CH:18]=[C:19]([C:22]3[O:23][C:24]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=4[CH3:33])=[N:25][N:26]=3)[CH:20]=[CH:21][C:15]=2[N:14]=1

Participants

9

Reactant 6

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 82110o-ToluohydrazideHCID 2724994Methyl N-(triethylammoniosulfonyl)carbamateHCID 669664013-{3,5-Dimethyl-4-[6-(5-o-tolyl-[1,3,4]oxadiazol-2-yl)-1H-benzoimidazol-2-yl]-phenyl}-2,2-dimethyl-propionic acid methyl esterHCID 669667662-[4-(2-Methoxycarbonyl-2-methyl-propyl)-2,6-dimethyl-phenyl]-3H-benzoimidazole-5-carboxylic acid

Product 1

HCID 252354593-{3,5-Dimethyl-4-[6-(5-o-tolyl-[1,3,4]oxadiazol-2-yl)-1H-benzoimidazol-2-yl]-phenyl}-2,2-dimethyl-propionic acid

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

3-{3,5-Dimethyl-4-[6-(5-o-tolyl-[1,3,4]oxadiazol-2-yl)-1H-benzoimidazol-2-yl]-phenyl}-2,2-dimethyl-propionic acid methyl ester. Add EDC (380 mg, 1.98 mmol) and HOBt (268 mg, 1.98 mmol) to a stirring solution of 2-[4-(2-methoxycarbonyl-2-methyl-propyl)-2,6-dimethyl-phenyl]-3H-benzoimidazole-5-carboxylic acid (626 mg, 1.65 mmol) and 2-methyl-benzoic acid hydrazide (248 mg, 1.65 mmol) in DMF (6 mL) under N2. Upon disappearance of the carboxylic acid by LC/MS, dilute the reaction with EtOAc (60 mL) and extract with water (20 mL) followed by brine (10 mL). Dry the organic phase over Na2SO4 and evaporate the solvent. Dissolve the residue in DMF (6 mL) and add Burgess reagent (1.18 g, 4.95 mmol). Heat the mixture my microwave irradiation to 150° C. for 15 min. Dilute the reaction with EtOAc (100 mL) and extract with water (25 mL). Extract the organic phase with saturated NaHCO3 (2×25 mL) followed by brine (20 mL). Dry the organic phase over Na2SO4 and evaporate the solvent. Purify the residue by silica gel chromatography (10-45% ACN/DCM) to afford the title compound as a yellow oil: (M+H)+495.3.

Workup

  1. extractionextract with water (20 mL)
  2. dry with materialDry the organic phase over Na2SO4
  3. customevaporate the solvent
  4. dissolutionDissolve the residue in DMF (6 mL)
  5. temperatureHeat
  6. customthe mixture my microwave irradiation to 150° C. for 15 min
  7. additionDilute
  8. extractionextract with water (25 mL)
  9. extractionExtract the organic phase with saturated NaHCO3 (2×25 mL)
  10. dry with materialDry the organic phase over Na2SO4
  11. customevaporate the solvent
  12. customPurify the residue by silica gel chromatography (10-45% ACN/DCM)

Sources & evidence

ORD record
ord-7dab397467b44dc2ac24497d62bd6c4b
Source dataset
uspto-grants-2012_07
Patent number
US08217065B2

Reaction notes

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