HCID 59004597, compound → HCID 178480157, compound

HRID 1668439Notes

Reaction equation

HRID 1668439 reaction equation
[CH2:1]([C:8]1[N:9]([CH2:20][CH2:21][CH:22]2[CH2:26][CH2:25][CH2:24][N:23]2[CH3:27])[C:10]2[C:15]([CH:16]=1)=[CH:14][C:13]([N+:17]([O-])=O)=[CH:12][CH:11]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.I.CS[C:31]([C:33]1[S:34][CH:35]=[CH:36][CH:37]=1)=[NH:32]>C(O)C.C(OCC)C.[Pd]>[CH2:1]([C:8]1[N:9]([CH2:20][CH2:21][CH:22]2[CH2:26][CH2:25][CH2:24][N:23]2[CH3:27])[C:10]2[C:15]([CH:16]=1)=[CH:14][C:13]([NH:17][C:31]([C:33]1[S:34][CH:35]=[CH:36][CH:37]=1)=[NH:32])=[CH:12][CH:11]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 2

HCID 59004597HCID 59004597, compoundHCID 66704664Methyl thiophene-2-carbimidothioate hydroiodide

Product 1

HCID 178480157HCID 178480157, compoundYield 49.3%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 3283Diethyl EtherSolvent

Procedure

Compound 4 (125 mg, 0.344 mmol) was dissolved in anhydrous ethanol (7 mL) in a dry argon purged flask. Palladium, 10 wt % on activated carbon (36.2 mg, 0.034 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 2M NH3 in methanol:CH2Cl2, 5:95 shows complete conversion to compound 5, 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 5 is charged to a small, argon purged flask fitted with a magnetic stirbar. Thiophene-2-carboximidothioic acid methyl ester hydroiodide (127.5 mg, 0.447 mmol) is added to the flask and the reaction was stirred under Ar at ambient temperature for 48 hours, at which time the solution was diluted with diethyl ether (100 ml) resulting in the formation of a off-white precipitate that was collected on a sintered glass funnel and washed with ether. The solid was partitioned between H2O and ethyl acetate and 3M sodium hydroxide solution added to adjust pH to 8-9. 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 sulphate, filtered, concentrated and the residue purified via chromatography on silica gel (2M NH3 in methanol:CH2Cl2, 5:95) to afford beige foam 6 (75 mg, 49.3%); 1H NMR (DMSO-d6) δ 7.71 (d, 1H, J=3.7 Hz), 7.58 (d, 1H, J=5.2 Hz), 7.35-7.20 (m, 6H), 7.09 (m, 1H), 6.92 (s, 1H), 6.64 (d, 1H, J=8.5 Hz), 6.23 (brs, 2H), 6.10 (s, 1H), 4.14 (s, 2H), 3.99 (t, 2H, J=8.0 Hz), 2.90 (quintet, 1H, J=4.6 Hz), 2.10 (s, 3H), 2.05-1.97 (m, 2H), 1.91-1.80 (m, 1H), 1.69-1.56 (m, 3H), 1.49-1.35 (m, 2H); ESI-MS (m/z, %): 443 (M+1, 70%), 219 (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 5 is charged to a small, argon purged flask
  7. customfitted with a magnetic stirbar
  8. stirringthe reaction was stirred under Ar at ambient temperature for 48 hours, at which time the solution
  9. customresulting in the formation of a off-white precipitate that
  10. customwas collected on a sintered glass funnel
  11. washwashed with ether
  12. customThe solid was partitioned between H2O and ethyl acetate and 3M sodium hydroxide solution
  13. additionadded
  14. customThe mixture was transferred to a separatory funnel
  15. customthe organic layer collected
  16. extractionThe aqueous layer was further extracted with ethyl acetate
  17. washthe combined organic layers were washed with brine
  18. dry with materialdried over magnesium sulphate
  19. filtrationfiltered
  20. concentrationconcentrated
  21. customthe residue purified via chromatography on silica gel (2M NH3 in methanol:CH2Cl2, 5:95)

Sources & evidence

ORD record
ord-19693593f69c44edbd3337b3de4cd0a4
Source dataset
uspto-grants-2011_08
Patent number
US07989447B2

Reaction notes

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