Hydrogen Sulfide → HCID 90913709, compound

HRID 1596680Notes

Reaction equation

HRID 1596680 reaction equation
[C:1]([C:3]1[CH:37]=[CH:36][C:6]([C:7]([N:9]2[CH2:35][CH2:34][C:12]3([N:16]([CH2:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[C:15](=[O:24])[N:14]([CH2:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C:13]3=[O:33])[CH2:11][CH2:10]2)=[O:8])=[CH:5][CH:4]=1)#[N:2].S.C([O-])(=O)C.[NH4+:43].C(=O)([O-])[O-].[K+].[K+].[CH3:50][C:51]([O:54][C:55]([O:57]C(OC(C)(C)C)=O)=O)([CH3:53])[CH3:52]>N1C=CC=CC=1.C(N(CC)CC)C.O>[C:51]([O:54][C:55]([NH:43][N:2]=[CH:1][C:3]1[CH:4]=[CH:5][C:6]([C:7]([N:9]2[CH2:35][CH2:34][C:12]3([N:16]([CH2:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[C:15](=[O:24])[N:14]([CH2:25][C:26]([O:28][C:29]([CH3:31])([CH3:32])[CH3:30])=[O:27])[C:13]3=[O:33])[CH2:11][CH2:10]2)=[O:8])=[CH:36][CH:37]=1)=[O:57])([CH3:53])([CH3:52])[CH3:50]

Participants

9

Reactant 5

HCID 402Hydrogen SulfideHCID 11430Potassium CarbonateHCID 90495Di-tert-butyl dicarbonateHCID 517165Ammonium AcetateHCID 57163162HCID 57163162, compound

Product 1

HCID 90913709HCID 90913709, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 1049PyridineSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
60 °C

Procedure

0.5 g (1.0 mmol) of the nitrile from Step E were dissolved in a mixture of 15 ml dry pyridine and 1.6 ml dry triethylamine. It was saturated with gaseous hydrogen sulfide, left at room temperature overnight, and poured into water. After three extractions with ethyl acetate the combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The residue was dissolved in 100 ml toluene, which was distilled off again in vacuo to remove traces of pyridine. To the remaining substance were added 5 ml acetone and 5 ml methyl iodide, and it was heated with reflux for 45 min, while a crystalline precipitate was formed. It was concentrated under reduced pressure, dissolved in 4 ml dry methanol, treated with 0.3 g (3.9 mmol) ammonium acetate and heated for 2 h at 60° C. The solvent was removed in vacuo, and the residue was stirred with ether. The solution was separated from the insoluble amidine, which was Boc-protected by dissolving in 10 ml of a 1:1 mixture of water and THF followed by addition of 0.9 g (6.5 mmol) potassium carbonate and 1.0 g (4.6 mmol) Boc2O and stirring for 1 hour at room temperature. It was diluted with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated under reduced pressure, and the title compound was isolated by chromatography on silica gel with dichloromethane/ethanol 96:4.

Workup

  1. extractionAfter three extractions with ethyl acetate the combined organic layers
  2. dry with materialwere dried over sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue was dissolved in 100 ml toluene
  5. distillationwhich was distilled off again in vacuo
  6. customto remove traces of pyridine
  7. additionTo the remaining substance were added 5 ml acetone and 5 ml methyl iodide, and it
  8. temperaturewas heated
  9. temperaturewith reflux for 45 min, while a crystalline precipitate
  10. customwas formed
  11. concentrationIt was concentrated under reduced pressure
  12. dissolutiondissolved in 4 ml dry methanol
  13. customThe solvent was removed in vacuo
  14. customThe solution was separated from the insoluble amidine, which
  15. dissolutionby dissolving in 10 ml of a 1:1 mixture of water and THF
  16. stirringstirring for 1 hour at room temperature
  17. extractionextracted with ethyl acetate
  18. dry with materialThe organic layer was dried over sodium sulfate
  19. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-de69f2d370fd4d3381e8035e887b3126
Source dataset
uspto-grants-2001_09
Patent number
US06291469B1

Reaction notes

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