Ammonia → HCID 178480155, compound

HRID 1668447Notes

Reaction equation

HRID 1668447 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]([NH2:18])=[CH:15][CH:16]=2)[CH:11]=[C:10]1[C:19]1[CH:24]=[CH:23][C:22]([N+:25]([O-:27])=[O:26])=[CH:21][CH:20]=1.I.CS[C:31]([C:33]1[S:34][CH:35]=[CH:36][CH:37]=1)=[NH:32].N>CO.C(Cl)Cl.C(O)C>[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:31]([C:33]3[S:34][CH:35]=[CH:36][CH:37]=3)=[NH:32])=[CH:15][CH:16]=2)[CH:11]=[C:10]1[C:19]1[CH:20]=[CH:21][C:22]([N+:25]([O-:27])=[O:26])=[CH:23][CH:24]=1

Participants

7

Reactant 3

HCID 222Ammonia2×HCID 59004664HCID 59004664, compoundHCID 66704664Methyl thiophene-2-carbimidothioate hydroiodide4×

Product 1

HCID 178480155HCID 178480155, compoundYield 27.8%

Reagents, catalysts & solvents 3

HCID 702EthanolSolvent2×HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

Compound 20 (97 mg, 0.266 mmol) and anhydrous ethanol (10 mL) were charged to a dry argon purged flask fitted with magnetic stirbar. Thiophene-2-carboximidothioic acid methyl ester hydroiodide (98.7 mg, 0.346 mmol) is added to the flask and the reaction was stirred under argon at ambient temperature for 46 hours at which time, thin layer chromatography in a solvent system of 2M NH3 in methanol:CH2Cl2, 5:95 (developed twice) shows incomplete consumption of 20. A condenser was added and the mixture heated to reflux for 5 hours. An additional amount of the thiophene-2-carboximidothioic acid methyl ester hydroiodide (0.2 eq) was added and stirring continued at 65° C. for an additional 24 hours. A further portion of thiophene-2-carboximidothioic acid methyl ester hydroiodide (0.2 eq) and ethanol (10 mL) were added and stirring continued for an additional 72 hours at reflux. Thin layer chromatography in a solvent system of 2M NH3 in methanol:CH2Cl2, 5:95 (developed twice) shows incomplete consumption of 20. A further portion of thiophene-2-carboximidothioic acid methyl ester hydroiodide (1.0 eq) was added and the mixture heated to reflux for 6 hours then stirred at ambient temperature for 48 hours. The mixture was filtered through a sintered glass funnel to remove insolubles, the filtrate concentrated and the residue purified using dry silica gel column chromatography eluting with 30 mL portions of solvent system (2M NH3 in methanol:CH2Cl2, 5:95) to afford an orange oil 21 (35 mg, 27.8%); 1H NMR (DMSO-d6) δ 8.36 (d, 2H, J=8.6 Hz), 8.18 (s, 1H), 7.86 (d, 2H, J=8.8 Hz), 7.75 (d, 1H, J=3.2 Hz), 7.61 (d, 1H, J=5.3 Hz), 7.52 (d, 1H, J=8.8 Hz), 7.14-7.05 (2×m, 2H), 6.85-6.80 (m, 1H), 6.69 (s, 1H), 4.29 (m, 2H), 2.91-2.84 (m, 1H), 2.08 and 2.06 (2×s, 3H), 2.03-1.93 (m, 1H), 1.90-1.78 (m, 1H), 1.72-1.63 (m, 1H), 1.61-1.43 (m, 3H), 1.37-1.20 (m, 2H); ESI-MS (m/z, %): 474 (M+1, 100%).

Workup

  1. customfitted with magnetic stirbar
  2. customconsumption of 20
  3. additionA condenser was added
  4. temperaturethe mixture heated
  5. temperatureto reflux for 5 hours
  6. stirringstirring
  7. waitcontinued for an additional 72 hours
  8. temperatureat reflux
  9. customconsumption of 20
  10. temperaturethe mixture heated
  11. temperatureto reflux for 6 hours
  12. stirringthen stirred at ambient temperature for 48 hours
  13. filtrationThe mixture was filtered through a sintered glass funnel
  14. customto remove insolubles
  15. concentrationthe filtrate concentrated
  16. customthe residue purified
  17. washeluting with 30 mL portions of solvent system (2M NH3 in methanol:CH2Cl2, 5:95)

Sources & evidence

ORD record
ord-c50277e0d28f4aa0ae1a17d1c8bcf184
Source dataset
uspto-grants-2011_08
Patent number
US07989447B2

Reaction notes

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