Dichloromethane → HCID 178478521, compound

HRID 547625Notes

Reaction equation

HRID 547625 reaction equation
[CH2:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH:2]1[N:10]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][C:26]2[CH:31]=[CH:30][C:29]([NH:32]C(OC(C)(C)C)=O)=[C:28]([NH:40][CH:41]=O)[CH:27]=2)=[CH:21][CH:20]=1)C(=O)OC(C)(C)C.FC(F)(F)C(O)=O.C(Cl)[Cl:51]>>[ClH:51].[ClH:51].[NH:32]1[C:29]2[CH:30]=[CH:31][C:26]([O:25][C:22]3[CH:23]=[CH:24][C:19]([CH2:18][NH:10][CH:2]4[CH2:3][C:4]5[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=5)[CH2:1]4)=[CH:20][CH:21]=3)=[CH:27][C:28]=2[N:40]=[CH:41]1

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 57585871HCID 57585871, compound

Product 1

HCID 178478521HCID 178478521, compound

Procedure

1,1-Dimethylethyl 2,3-dihydro-1H-inden-2-yl[(4-{[4-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-3-(formylamino)phenyl]oxy}phenyl)methyl]carbamate (365 mg, 0.637 mmol) was dissolved in 20 mL of methylene chloride and stirred with 4 mL trifluoroacetic acid for approximately 18 hours. The reaction was concentrated and purified using preparative HPLC. Pure fractions were combined, diluted with ethyl acetate and washed with 1N NaOH. The aqueous layer was extracted with ethyl acetate. The organic layers were combined, dried over MgSO4 and concentrated. The residue was dissolved in ethyl acetate. 4N HCl in dioxane was added and N-{[4-(1H-benzimidazol-5-yloxy) phenyl]methyl}-2,3-dihydro-1H-inden-2-amine dihydrochloride was collected by filtration as a white precipitate. The solid was dissolved in methanol, concentrated onto basic alumina and purified by column chromatography using an ISCO™ amine functionalized silica column. (dichloromethane to 5% methanol). The purified material was dissolved in minimal methanol. HCl (4N in dioxane) was added to the solution which was concentrated to give N-{[4-(1H-benzimidazol-5-yloxy)phenyl]methyl}-2,3-dihydro-1H-inden-2-amine dihydrochloride. (Example No. 26)

Workup

  1. concentrationThe reaction was concentrated
  2. custompurified
  3. additiondiluted with ethyl acetate
  4. washwashed with 1N NaOH
  5. extractionThe aqueous layer was extracted with ethyl acetate
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in ethyl acetate
  9. addition4N HCl in dioxane was added
  10. filtrationN-{[4-(1H-benzimidazol-5-yloxy) phenyl]methyl}-2,3-dihydro-1H-inden-2-amine dihydrochloride was collected by filtration as a white precipitate
  11. dissolutionThe solid was dissolved in methanol
  12. concentrationconcentrated onto basic alumina
  13. custompurified by column chromatography
  14. dissolutionThe purified material was dissolved in minimal methanol. HCl (4N in dioxane)
  15. additionwas added to the solution which
  16. concentrationwas concentrated

Sources & evidence

ORD record
ord-c31dc1d2cf2b4e18a4d4890074e60c69
Source dataset
uspto-grants-2011_05
Patent number
US07939528B2

Reaction notes

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