2-Bromo-N-[4-(2-furyl)-5-(tetrahydropyran-4-ylcarbonyl)thiazol-2-yl]acetamide → N-[4-(2-Furyl)-5-(tetrahydropyran-4-ylcarbonyl)thiazol-2-yl]-2-[(7S,8aS)-7-hydroxyoctahydropyrrolo[1,2-a]pyrazin-2-yl]acetamide

HRID 1361867Notes

Reaction equation

HRID 1361867 reaction equation
Br[CH2:2][C:3]([NH:5][C:6]1[S:7][C:8]([C:16]([CH:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)=[O:17])=[C:9]([C:11]2[O:12][CH:13]=[CH:14][CH:15]=2)[N:10]=1)=[O:4].O1CCCCC1[O:30][C@@H:31]1[CH2:39][N:34]2[CH2:35][CH2:36][NH:37][CH2:38][C@@H:33]2[CH2:32]1>C1COCC1>[O:12]1[CH:13]=[CH:14][CH:15]=[C:11]1[C:9]1[N:10]=[C:6]([NH:5][C:3](=[O:4])[CH2:2][N:37]2[CH2:36][CH2:35][N:34]3[CH2:39][C@@H:31]([OH:30])[CH2:32][C@H:33]3[CH2:38]2)[S:7][C:8]=1[C:16]([CH:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1)=[O:17]

Participants

4

Reactant 2

HCID 231445052-Bromo-N-[4-(2-furyl)-5-(tetrahydropyran-4-ylcarbonyl)thiazol-2-yl]acetamideHCID 66968036(7S,8aS)-7-(tetrahydropyran-2-yl)oxyoctahydropyrrolo[1,2-a]pyrazine

Product 1

HCID 86612470N-[4-(2-Furyl)-5-(tetrahydropyran-4-ylcarbonyl)thiazol-2-yl]-2-[(7S,8aS)-7-hydroxyoctahydropyrrolo[1,2-a]pyrazin-2-yl]acetamideYield 34%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Compound 531 (120 mg, 0.300 mmol) was dissolved in THF (2 mL), and (7S,8aS)-7-(tetrahydropyran-2-yl)oxyoctahydropyrrolo[1,2-a]pyrazine (204 mg, 0.900 mmol) was added thereto, followed by stirring at room temperature for 2.5 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was dissolved in ethanol (3 mL), and 2 mol/L hydrochloric acid (3 mL) was added thereto, followed by stirring overnight at room temperature. The reaction mixture was concentrated under reduced pressure, and the resulting residue was poured into water. A 2 mol/L sodium hydroxide solution added thereto to adjust the pH to 8, followed by extraction with chloroform. The organic layer was washed with a solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled away under reduced pressure. The resulting residue was purified through silica gel column chromatography (chloroform:methanol=23:2), followed by recrystallizing from a mixed solvent of ethanol and diethyl ether to afford the entitled Compound 569 (46.5 mg, 34%).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe resulting residue was dissolved in ethanol (3 mL)
  3. addition2 mol/L hydrochloric acid (3 mL) was added
  4. stirringby stirring overnight at room temperature
  5. concentrationThe reaction mixture was concentrated under reduced pressure
  6. additionthe resulting residue was poured into water
  7. additionA 2 mol/L sodium hydroxide solution added
  8. extractionfollowed by extraction with chloroform
  9. washThe organic layer was washed with a solution of sodium chloride
  10. dry with materialdried over anhydrous magnesium sulfate
  11. distillationthe solvent was distilled away under reduced pressure
  12. customThe resulting residue was purified through silica gel column chromatography (chloroform:methanol=23:2)
  13. customby recrystallizing from a mixed solvent of ethanol and diethyl ether

Sources & evidence

ORD record
ord-90c4997dd3d94df98fcfd43ce0d0b0e8
Source dataset
uspto-grants-2011_02
Patent number
US07880013B2

Reaction notes

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