Ammonia → HCID 178511871, compound

HRID 1668445Notes

Reaction equation

HRID 1668445 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:11]([CH2:20][CH2:21][N:22]3[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]3)[C:12]3[C:17]([CH:18]=2)=[CH:16][C:15]([NH2:19])=[CH:14][CH:13]=3)=[CH:6][CH:5]=1)([O-:3])=[O:2].C(O)C.I.CS[C:34]([C:36]1[S:37][CH:38]=[CH:39][CH:40]=1)=[NH:35].N>CO.C(OCC)C.C(Cl)Cl>[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:11]([CH2:20][CH2:21][N:22]3[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]3)[C:12]3[C:17]([CH:18]=2)=[CH:16][C:15]([NH:19][C:34]([C:36]2[S:37][CH:38]=[CH:39][CH:40]=2)=[NH:35])=[CH:14][CH:13]=3)=[CH:6][CH:5]=1)([O-:3])=[O:2]

Participants

8

Reactant 4

HCID 222AmmoniaHCID 702EthanolHCID 59004627HCID 59004627, compoundHCID 66704664Methyl thiophene-2-carbimidothioate hydroiodide3×

Product 1

HCID 178511871HCID 178511871, compoundYield 21.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

Compound 17 (250 mg, 0.686 mmol) and anhydrous ethanol (15 mL) were charged to a dry argon purged flask fitted with magnetic stirbar. Thiophene-2-carboximidothioic acid methyl ester hydroiodide (254.3 mg, 0.891 mmol) is added to the flask and the reaction was stirred under argon at ambient temperature for 48 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 17. 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) was added and stirring continued for an additional 18 hours at reflux. After cooling to room temperature, the solution was diluted with diethyl ether (150 ml) resulting in the formation of 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 9-10. 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, 2.5:97.5) to afford orange-yellow solid 18 (69 mg, 21.2%); 1H NMR (DMSO-d6) δ 8.35 (d, 2H, J=8.7 Hz), 7.93 (d, 2H, J=8.7 Hz), 7.73 (d, 1H, J=3.7 Hz), 7.60 (d, 1H, J=5.3 Hz), 7.51 (d, 1H, J=8.6 Hz), 7.10 (m, 1H), 7.07 (s, 1H), 6.80 (d, 1H, J=8.5 Hz), 6.66 (s, 1H), 6.32 (brs, 2H), 4.32 (t, 2H, J=6.5 Hz), 2.49 (m, 2H), 2.21 (m, 4H), 1.31 (m, 6H); ESI-MS (m/z, %): 474 (M+1, 100%).

Workup

  1. customfitted with magnetic stirbar
  2. customconsumption of 17
  3. additionA condenser was added
  4. temperaturethe mixture heated
  5. temperatureto reflux for 5 hours
  6. stirringstirring
  7. waitcontinued for an additional 18 hours
  8. temperatureat reflux
  9. customresulting in the formation of 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, 2.5:97.5)

Sources & evidence

ORD record
ord-7175a7fccbaf4a44b27074184b8323c9
Source dataset
uspto-grants-2011_08
Patent number
US07989447B2

Reaction notes

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