Water → HCID 58065433, compound

HRID 909535Notes

Reaction equation

HRID 909535 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([C:14]2[N:15](C(OC(C)(C)C)=O)[C:16]([C:19]3[S:20][CH:21]=[CH:22][N:23]=3)=[CH:17][CH:18]=2)[CH:5]=[C:6]([O:8][C@@H:9]([CH3:13])[CH2:10][O:11][CH3:12])[CH:7]=1.Cl[C:32]1[N:33]=[CH:34][C:35]([C:38]([O:40][CH3:41])=[O:39])=[N:36][CH:37]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[CH3:12][O:11][CH2:10][C@H:9]([CH3:13])[O:8][C:6]1[CH:7]=[C:2]([CH:3]=[C:4]([C:14]2[NH:15][C:16]([C:19]3[S:20][CH:21]=[CH:22][N:23]=3)=[CH:17][CH:18]=2)[CH:5]=1)[O:1][C:32]1[N:33]=[CH:34][C:35]([C:38]([O:40][CH3:41])=[O:39])=[N:36][CH:37]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 406081Methyl 5-chloropyrazine-2-carboxylateHCID 66681373t-Butyl 2-{3-hydroxy-5-[(1S)-2-methoxy-1-methylethoxy]phenyl}-5-(1,3-thiazol-2-yl)-1H-pyrrole-1-carboxylate

Product 1

HCID 58065433HCID 58065433, compoundYield 93%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

t-Butyl 2-{3-hydroxy-5-[(1S)-2-methoxy-1-methylethoxy]phenyl}-5-(1,3-thiazol-2-yl)-1H-pyrrole-1-carboxylate (200 mg, 0.464 mmol) synthesized in Example (38d) and methyl 5-chloropyrazine-2-carboxylate (120 mg, 0.695 mmol) synthesized in Example (62b) were dissolved in N,N-dimethylformamide (10 mL), and potassium carbonate (257 mg, 1.86 mmol) was added, followed by stirring at 80° C. for 7 hours under nitrogen atmosphere. The reaction solution was cooled to room temperature, water (40 mL) was added, and extraction was carried out with ethyl acetate (40 mL). The organic layer was washed with saturated brine, and subsequently dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=0%-50%). The resulting yellow solid was dissolved in dichloromethane (2 mL), and trifluoroacetic acid (4 mL) was added, followed by stirring at room temperature for 1.5 hours. To the reaction solution, a saturated aqueous sodium hydrogencarbonate solution (40 mL) was added, and extraction was carried out twice with ethyl acetate (40 mL). The organic layer was washed with saturated brine, and subsequently dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=0%-50%) to afford the desired compound (164 mg, yield 93%) as a yellow solid.

Workup

  1. temperatureThe reaction solution was cooled to room temperature
  2. extractionextraction
  3. washThe organic layer was washed with saturated brine
  4. dry with materialsubsequently dried over anhydrous magnesium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. customthe resulting residue was purified
  7. washsilica gel column chromatography (elution solvent: ethyl acetate/hexane=0%-50%)
  8. dissolutionThe resulting yellow solid was dissolved in dichloromethane (2 mL)
  9. additiontrifluoroacetic acid (4 mL) was added
  10. stirringby stirring at room temperature for 1.5 hours
  11. additionTo the reaction solution, a saturated aqueous sodium hydrogencarbonate solution (40 mL) was added
  12. extractionextraction
  13. washThe organic layer was washed with saturated brine
  14. dry with materialsubsequently dried over anhydrous magnesium sulfate
  15. distillationThe solvent was distilled off under reduced pressure
  16. customthe resulting residue was purified
  17. washsilica gel column chromatography (elution solvent: ethyl acetate/hexane=0%-50%)

Sources & evidence

ORD record
ord-6c167f5558264c5889a1326d9577f446
Source dataset
uspto-grants-2011_09
Patent number
US08017610B2

Reaction notes

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