Acetic Acid → 2-[6-(2,2-Dimethylpropyl)-1H-benzimidazol-2-yl]-2,3-dihydro-1H-inden-2-amine

HRID 1424157Notes

Reaction equation

HRID 1424157 reaction equation
C([CH:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH2:10][C:9]1([NH2:20])[C:17](O)=O)(OC(C)(C)C)=O.CN1CCOCC1.C(OC(Cl)=O)C(C)C.[CH2:36]([C:41]1[CH:42]=[C:43]([NH2:48])[C:44]([NH2:47])=[CH:45][CH:46]=1)[C:37]([CH3:40])([CH3:39])[CH3:38].C(O)(=O)C.FC(F)(F)C(O)=O>C(#N)C>[CH3:38][C:37]([CH3:40])([CH3:39])[CH2:36][C:41]1[CH:46]=[CH:45][C:44]2[N:47]=[C:17]([C:9]3([NH2:20])[CH2:8][C:16]4[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=4)[CH2:10]3)[NH:48][C:43]=2[CH:42]=1

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 6422Trifluoroacetic acidHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 569237992-Amino-1-[(2-methylpropan-2-yl)oxycarbonyl]-1,3-dihydroindene-2-carboxylic acidHCID 866990534-Neopentylbenzene-1,2-diamine

Product 1

HCID 866990542-[6-(2,2-Dimethylpropyl)-1H-benzimidazol-2-yl]-2,3-dihydro-1H-inden-2-amineYield 52%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of Boc-2-aminoindane-2-carboxylic acid (107 mg, 0.386 mmol) in acetonitrile (2.0 mL) and 4-methylmorpholine (0.11 mL, 1.0 mmol) cooled in an ice/brine bath was added isobutylchloroformate (0.050 mL, 0.38 mmol). The mixture was stirred for 30 minutes and then 4-neopentylbenzene-1,2-diamine (Preparation 83, 82 mg, 0.46 mmol) was added. The reaction mixture was allowed to warm to room temperature and stir for 4 hours. The solvent was evaporated and the resulting oil was dissolved in acetic acid (3.0 mL, 50 mmol) and heated at 65° C. for 16 hours. After cooling, the solvent was removed in vacuo and the residue purified by silica gel column chromatography eluting with a 0-100% ethyl acetate/hexanes gradient. The resulting oil was dissolved in methylene chloride (5 mL) and treated with trifluoroacetic acid (0.5 mL, 6 mmol). After stirring for 2 hours, the reaction mixture was concentrated in vacuo and purified by silica gel column chromatography eluting with a 0-100% CMA80/methylene chloride gradient. This provided the title compound (63.7 mg, 52%) as a white solid.

Workup

  1. stirringstir for 4 hours
  2. customThe solvent was evaporated
  3. temperatureheated at 65° C. for 16 hours
  4. temperatureAfter cooling
  5. customthe solvent was removed in vacuo
  6. customthe residue purified by silica gel column chromatography
  7. washeluting with a 0-100% ethyl acetate/hexanes gradient
  8. dissolutionThe resulting oil was dissolved in methylene chloride (5 mL)
  9. stirringAfter stirring for 2 hours
  10. concentrationthe reaction mixture was concentrated in vacuo
  11. custompurified by silica gel column chromatography
  12. washeluting with a 0-100% CMA80/methylene chloride gradient

Sources & evidence

ORD record
ord-543dd50724484c05bacaca13356c5c57
Source dataset
uspto-grants-2015_01
Patent number
US08927587B2

Reaction notes

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