HCID 57474480, compound → HCID 178511926, compound

HRID 552979Notes

Reaction equation

HRID 552979 reaction equation
[N:1]1([CH2:6][CH2:7][CH2:8][CH2:9][N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([N+:19]([O-])=O)[CH:17]=3)[CH:12]=[CH:11]2)[CH:5]=[CH:4][N:3]=[CH:2]1.I.CS[C:25]([C:27]1[S:28][CH:29]=[CH:30][CH:31]=1)=[NH:26]>C(O)C.C(OCC)C.[Pd]>[N:1]1([CH2:6][CH2:7][CH2:8][CH2:9][N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([NH:19][C:25]([C:27]4[S:28][CH:29]=[CH:30][CH:31]=4)=[NH:26])[CH:17]=3)[CH:12]=[CH:11]2)[CH:5]=[CH:4][N:3]=[CH:2]1

Participants

6

Reactant 2

HCID 57474480HCID 57474480, compound2×HCID 66704664Methyl thiophene-2-carbimidothioate hydroiodide

Product 1

HCID 178511926HCID 178511926, compoundYield 54.5%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 3283Diethyl EtherSolvent

Procedure

1-(4-(1H-imidazol-1-yl)butyl)-6-nitro-1H-indole (compound 166, 145 mg, 0.510 mmol) was dissolved in anhydrous ethanol (7 mL) in a dry argon purged flask. Palladium, 10 wt % on activated carbon (54.2 mg, 0.051 mmol) is quickly added and the atmosphere from the flask evacuated by vacuum pump and replaced with hydrogen from a balloon. The atmosphere is evacuated from the flask and replaced with hydrogen twice more and the mixture stirred under a hydrogen atmosphere at room temperature. After 3 hours, thin layer chromatography in a solvent system of (10% 2M NH3 in methanol/90% dichloromethane) shows complete conversion to compound 167, 1-(4-(1H-imidazol-1-yl)butyl)-1H-indol-6-amine, which is utilized without isolation. The mixture is filtered through a pad of celite to remove insolubles, the pad washed with anhydrous ethanol (7 mL) and the ethanolic solution of the amine 167 is charged to a small, argon purged flask fitted with a magnetic stir bar. Thiophene-2-carboximidothioic acid methyl ester hydroiodide (189.1 mg, 0.663 mmol) is added to the flask and the reaction was stirred under Ar at ambient temperature for 20 hours, at which time the solution was diluted with diethyl ether (100 ml) resulting in the formation of a sticky solid which could not be isolated via filtration. As a result the product was washed off the funnel with methanol, combined with the filtrate and solvents evaporated to leave a crude residue. The residue was partitioned between H2O and ethyl acetate and 3M sodium hydroxide solution added to adjust pH to 9. The mixture was transferred to a separatory funnel and the organic layer collected. The aqueous layer was further extracted with ethyl acetate and the combined organic layers were washed with brine, dried over magnesium sulfate, filtered, concentrated and the residue purified via chromatography on silica gel (2.5% 2M NH3 in methanol/97.5% dichloromethane) to yield yellow solid, compound 168 (101 mg, 54.5% yield); 1H-NMR (DMSO-d6) δ 7.74 (d, 1H, J=3.0), 7.60 (d, 1H, J=5.2), 7.56 (s, 1H), 7.45 (d, 1H, J=8.3), 7.21 (d, 1H, J=3.0), 7.13-7.06 (m, 2H), 6.92 (s, 1H), 6.85 (s, 1H), 6.59 (d, 1H, J=8.0), 6.42-6.30 (br, 2×m, 3H), 4.17-4.06 (m, 2H), 3.99-3.92 (m, 2H), 1.75-1.58 (m, 4H); MS (ESI+): 364 (M+1, 100%).

Workup

  1. customthe atmosphere from the flask evacuated by vacuum pump
  2. customThe atmosphere is evacuated from the flask
  3. filtrationThe mixture is filtered through a pad of celite
  4. customto remove insolubles
  5. washthe pad washed with anhydrous ethanol (7 mL)
  6. additionthe ethanolic solution of the amine 167 is charged to a small, argon purged flask
  7. customfitted with a magnetic stir bar
  8. stirringthe reaction was stirred under Ar at ambient temperature for 20 hours, at which time the solution
  9. customresulting in the formation of a sticky solid which could not
  10. custombe isolated via filtration
  11. customAs a result the product
  12. washwas washed off the funnel with methanol
  13. customevaporated
  14. customto leave a crude residue
  15. customThe residue was partitioned between H2O and ethyl acetate and 3M sodium hydroxide solution
  16. additionadded
  17. customThe mixture was transferred to a separatory funnel
  18. customthe organic layer collected
  19. extractionThe aqueous layer was further extracted with ethyl acetate
  20. washthe combined organic layers were washed with brine
  21. dry with materialdried over magnesium sulfate
  22. filtrationfiltered
  23. concentrationconcentrated
  24. customthe residue purified via chromatography on silica gel (2.5% 2M NH3 in methanol/97.5% dichloromethane)

Sources & evidence

ORD record
ord-1f44924af38f49f4bf184fde03cf7822
Source dataset
uspto-grants-2011_05
Patent number
US07951940B2

Reaction notes

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