Potassium Carbonate → HCID 57886922, compound

HRID 1819319Notes

Reaction equation

HRID 1819319 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:6]([CH2:7][N:8]=[C:9]=[O:10])=[CH:5][CH:4]=1.[C:13](=O)([O-])[O-].[K+].[K+].[NH2:19][C:20]1[C:24]([C:25]#[N:26])=[C:23]([N:27]2[CH2:32][CH2:31][CH2:30][C@@H:29]([NH:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:28]2)[N:22]([CH2:41][C:42]2[CH:47]=[C:46]([F:48])[CH:45]=[CH:44][C:43]=2[Cl:49])[C:21]=1[C:50]([O:52]CC)=O>N1C=CC=CC=1>[Cl:49][C:43]1[CH:44]=[CH:45][C:46]([F:48])=[CH:47][C:42]=1[CH2:41][N:22]1[C:21]2[C:50](=[O:52])[N:8]([CH2:7][C:6]3[CH:11]=[CH:12][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[C:9](=[O:10])[N:19]([CH3:13])[C:20]=2[C:24]([C:25]#[N:26])=[C:23]1[N:27]1[CH2:32][CH2:31][CH2:30][C@@H:29]([NH:33][C:34](=[O:35])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])[CH2:28]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 187910Isocyanic acid, p-methoxybenzyl-2×HCID 57886960HCID 57886960, compound

Product 1

HCID 57886922HCID 57886922, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
130 °C

Procedure

4-Methoxybenzyl isocyanate (0.5 ml) and potassium carbonate (486 mg) were added to a solution of ethyl 3-amino-5-{(3R)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}-1-(2-chloro-5-fluorobenzyl)-4-cyano-1H-pyrrole-2-carboxylate (920 mg) in pyridine (1 ml), and the resulting mixture was stirred at 130° C. for 6 hours. 4-Methoxybenzyl isocyanate (2.0 ml) was added thereto, followed by stirring with heating for another 24 hours. The reaction solution was cooled to 25° C. and then concentrated under reduced pressure and water was added to the residue, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and then filtered and the filtrate was concentrated under reduced pressure. The residue was dissolved in N,N-dimethylformamide (15 ml), followed by adding thereto potassium carbonate (486 mg) and methyl iodide (0.33 ml), and the resulting mixture was stirred at 25° C. for 3 hours. A saturated aqueous ammonium chloride solution was added to the reaction solution, followed by extraction with chloroform. The organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and then filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (750 mg) as a light-yellow amorphous substance.

Workup

  1. stirringby stirring
  2. temperaturewith heating for another 24 hours
  3. temperatureThe reaction solution was cooled to 25° C.
  4. concentrationconcentrated under reduced pressure and water
  5. additionwas added to the residue
  6. extractionfollowed by extraction with chloroform
  7. washThe organic layer was washed with a saturated aqueous sodium chloride solution
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationthe filtrate was concentrated under reduced pressure
  11. dissolutionThe residue was dissolved in N,N-dimethylformamide (15 ml)
  12. additionby adding
  13. stirringpotassium carbonate (486 mg) and methyl iodide (0.33 ml), and the resulting mixture was stirred at 25° C. for 3 hours
  14. additionA saturated aqueous ammonium chloride solution was added to the reaction solution
  15. extractionfollowed by extraction with chloroform
  16. washThe organic layer was washed with water
  17. dry with materiala saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate
  18. filtrationfiltered
  19. concentrationthe filtrate was concentrated under reduced pressure
  20. customThe resulting residue was purified by a silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-85ff0cd0ac9b43a4825ce4eabedc6c1f
Source dataset
uspto-grants-2009_10
Patent number
US07601728B2

Reaction notes

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