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 methyl ester

HRID 1360800Notes

Reaction equation

HRID 1360800 reaction equation
C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[CH3:15][O:16][C:17]([C:19]([CH3:42])([CH3:41])[CH2:20][C:21]1[CH:26]=[C:25]([CH3:27])[C:24]([C:28]2[NH:29][C:30]3[CH:36]=[C:35]([C:37](O)=[O:38])[CH:34]=[CH:33][C:31]=3[N:32]=2)=[C:23]([CH3:40])[CH:22]=1)=[O:18].[CH3:43][C:44]1[CH:53]=[CH:52][CH:51]=[CH:50][C:45]=1[C:46]([NH:48][NH2:49])=O.CC[N+](S(N=C(OC)[O-])(=O)=O)(CC)CC>CN(C=O)C.CCOC(C)=O>[CH3:15][O:16][C:17](=[O:18])[C:19]([CH3:41])([CH3:42])[CH2:20][C:21]1[CH:22]=[C:23]([CH3:40])[C:24]([C:28]2[NH:29][C:30]3[CH:36]=[C:35]([C:37]4[O:38][C:46]([C:45]5[CH:50]=[CH:51][CH:52]=[CH:53][C:44]=5[CH3:43])=[N:48][N:49]=4)[CH:34]=[CH:33][C:31]=3[N:32]=2)=[C:25]([CH3:27])[CH:26]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 82110o-ToluohydrazideHCID 2724994Methyl N-(triethylammoniosulfonyl)carbamateHCID 669667662-[4-(2-Methoxycarbonyl-2-methyl-propyl)-2,6-dimethyl-phenyl]-3H-benzoimidazole-5-carboxylic acid

Product 1

HCID 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 ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

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-0e46fa10cbeb4d14b01eb98226b2fa08
Source dataset
uspto-grants-2011_02
Patent number
US07879850B2

Reaction notes

Loading…