Isobutyl chloroformate → HCID 136333929, compound

HRID 1426443Notes

Reaction equation

HRID 1426443 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH:13]([C:14](O)=O)[CH2:12][N:11]2[CH2:17][CH2:18][CH2:19][C@@H:10]2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)(=O)OCC(C)C.[NH2:28][C:29]1[CH:33]=[C:32]([Br:34])[S:31][C:30]=1[C:35]([NH2:37])=[O:36].C(=O)([O-])O.[Na+]>O1CCCC1.C(N(CC)CC)C>[Br:34][C:32]1[S:31][C:30]2[C:35](=[O:36])[NH:37][C:14]([CH:13]3[CH2:12][N:11]4[CH2:17][CH2:18][CH2:19][C@@H:10]4[CH2:9][N:8]3[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])=[N:28][C:29]=2[CH:33]=1

Participants

7

Reactant 4

HCID 62365Isobutyl chloroformateHCID 516892Sodium BicarbonateHCID 219758623-Amino-5-bromothiophene-2-carboxamideHCID 71147240HCID 71147240, compound

Product 1

HCID 136333929HCID 136333929, compoundYield 14.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

To a mixture of (8aR)-2-(tert-butoxycarbonyl)octahydropyrrolo[1,2-a]pyrazine-3-carboxylic acid (270 mg), triethylamine (0.18 mL) and tetrahydrofuran (10 mL) was added 2-methylpropyl chlorocarbonate (0.13 mL) with stirring at room temperature. After 2 hr, 3-amino-5-bromothiophene-2-carboxamide (221 mg) produced in Example 1, step D, was added and the mixture was stirred at 50° C. for 2 hr. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate, and extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate. Insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was dissolved in ethanol (10 mL), 2M aqueous sodium hydroxide solution (2 mL) was added, and the mixture was stirred at 80° C. for 2 hr. The reaction mixture was allowed to cool to room temperature, and poured into saturated aqueous sodium hydrogen carbonate. The mixture was extracted with ethyl acetate/tetrahydrofuran mixture, and the extract was dried over anhydrous magnesium sulfate. Insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (methanol/ethyl acetate) to give the title compound (65 mg) as a yellow solid.

Workup

  1. stirringthe mixture was stirred at 50° C. for 2 hr
  2. extractionextracted with ethyl acetate
  3. dry with materialThe extract was dried over anhydrous magnesium sulfate
  4. customInsoluble material was removed by filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. dissolutionThe residue was dissolved in ethanol (10 mL)
  7. addition2M aqueous sodium hydroxide solution (2 mL) was added
  8. stirringthe mixture was stirred at 80° C. for 2 hr
  9. temperatureto cool to room temperature
  10. additionpoured into saturated aqueous sodium hydrogen carbonate
  11. extractionThe mixture was extracted with ethyl acetate/tetrahydrofuran mixture
  12. dry with materialthe extract was dried over anhydrous magnesium sulfate
  13. customInsoluble material was removed by filtration
  14. concentrationthe filtrate was concentrated under reduced pressure
  15. customThe residue was purified by basic silica gel column chromatography (methanol/ethyl acetate)

Sources & evidence

ORD record
ord-a7c5c6ed53ff4c12940a057e55b2fbb1
Source dataset
uspto-grants-2015_01
Patent number
US08933069B2

Reaction notes

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