HCID 59004612, compound → HCID 178480160, compound

HRID 1668443Notes

Reaction equation

HRID 1668443 reaction equation
[CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][CH:3]1[CH2:7][CH2:8][N:9]1[C:17]2[C:12](=[CH:13][C:14]([N+:18]([O-])=O)=[CH:15][CH:16]=2)[CH:11]=[C:10]1[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][C:29]([F:32])([F:31])[F:30])=[CH:24][CH:23]=1.I.CS[C:36]([C:38]1[S:39][CH:40]=[CH:41][CH:42]=1)=[NH:37]>C(O)C.C(OCC)C.[Pd]>[CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][CH:3]1[CH2:7][CH2:8][N:9]1[C:17]2[C:12](=[CH:13][C:14]([NH:18][C:36]([C:38]3[S:39][CH:40]=[CH:41][CH:42]=3)=[NH:37])=[CH:15][CH:16]=2)[CH:11]=[C:10]1[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][C:29]([F:32])([F:31])[F:30])=[CH:24][CH:23]=1

Participants

6

Reactant 2

HCID 59004612HCID 59004612, compoundHCID 66704664Methyl thiophene-2-carbimidothioate hydroiodide

Product 1

HCID 178480160HCID 178480160, compoundYield 53.7%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 3283Diethyl EtherSolvent

Procedure

Compound 12 (95 mg, 0.212 mmol) was dissolved in anhydrous ethanol (10 mL) in a dry argon purged flask. Palladium, 10 wt % on activated carbon (22.6 mg, 0.0212 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 MeOH:CH2Cl2, 5:95 shows complete conversion to 13, which is utilized without isolation. The mixture is filtered through a pad of celite to remove insolubles, the pad washed with anhydrous ethanol (5 mL) and the ethanolic solution of the amine 13 is charged to a small, argon purged flask fitted with a magnetic stirbar. Thiophene-2-carboximidothioic acid methyl ester hydroiodide (78.6 mg, 0.276 mmol) is added to the flask and the reaction was stirred under argon at ambient temperature for 44 hours. The solution was diluted with diethyl ether (100 ml) and cooled in an ice bath. No precipitate formed thus the solvent was evaporated. The residue was partitioned between H2O and ethyl acetate and 1M 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 sulphate, filtered, concentrated and the crude freebase purified via chromatography on silica gel (2M NH3 in MeOH:CH2Cl2, 2.5:97.5 to 5:95) to yield compound 14 (60 mg, 53.7%) as a yellow solid. 1H NMR (DMSO-d6) δ 1.36-48 (m, 2H), 1.53-1.60 (m, 3H), 1.80-1.86 (m, 1H), 1.92-2.05 (m, 2H), 2.08 (s, 3H), 2.87-2.93 (m, 1H), 4.00 (t, 2H, J=8.0 Hz), 4.19 (s, 2H), 6.12 (s, 1H), 6.23 (brs, 2H), 6.63-6.67 (m, 1H), 6.93 (s, 1H), 7.07-7.10 (m, 1H), 7.26 (d, 1H, J=8.6 Hz), 7.31-7.41 (m, 4H), 7.5 8 (d, 1H, J=5.3 Hz), 7.71 (d, 1H, J=3.7 Hz); ESI-MS (m/z, %): 527 (MH+, 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 (5 mL)
  6. additionthe ethanolic solution of the amine 13 is charged to a small, argon purged flask
  7. customfitted with a magnetic stirbar
  8. stirringthe reaction was stirred under argon at ambient temperature for 44 hours
  9. temperaturecooled in an ice bath
  10. customNo precipitate formed thus the solvent
  11. customwas evaporated
  12. customThe residue was partitioned between H2O and ethyl acetate and 1M 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 crude freebase purified via chromatography on silica gel (2M NH3 in MeOH:CH2Cl2, 2.5:97.5 to 5:95)

Sources & evidence

ORD record
ord-7d2fc5f1ba984d31abf1579d9098b08d
Source dataset
uspto-grants-2011_08
Patent number
US07989447B2

Reaction notes

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