Acetamide → tert-butyl 2-amino-4H,5H,6H,7H-[1,3]thiazolo[5,4-c]pyridine-5-carboxylate

HRID 418341Notes

Reaction equation

HRID 418341 reaction equation
[C:1]([O:5][C:6]([N:8]1CCC(=O)CC1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:15]1[CH2:19]CCC1.C[C:21]1[CH:22]=[CH:23][C:24]([S:27](O)(=O)=O)=[CH:25]C=1.C([NH2:34])(=O)C>C1CCCCC1.O>[C:1]([O:5][C:6]([N:8]1[CH2:21][CH2:22][C:23]2[N:34]=[C:19]([NH2:15])[S:27][C:24]=2[CH2:25]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 178AcetamideHCID 6101p-Toluenesulfonic acidHCID 31268PyrrolidineHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 11357283tert-butyl 2-amino-4H,5H,6H,7H-[1,3]thiazolo[5,4-c]pyridine-5-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8078CyclohexaneSolvent

Procedure

Dissolved 4-Oxo-piperidine-1-carboxylic acid tert-butyl ester (15.0 g, 75.28 mmol) in 75 mL of cyclohexane. To this was added pyrrolidine (6.70 mL, 79.00 mmol) and a catalytic amount of TsOH. The mixture was refluxed with a Dean-Stark trap until no water was collected (5 h). The mixture was filtered and concentrated to an oily brown residue. The residue was dissolved in 25 mL of anhydrous MeOH. To this mixture was added S(0) (2.40 g). The mixture was cooled in and ice bath and acetamide (3.19 g, 76.00 mmol) was added in portions. After 2 h and warming to room temperature a thick tan ppt. appeared. Filtered the material and washed with cold MeOH to give 10.04 g. A second ppt., 3.64 g, was collected. 1H NMR indicated identical material and these were combined to give 2-amino-6,7-dihydro-4H-thiazolo[5,4-c]pyridine-5-carboxylic acid tert-butyl ester.

Workup

  1. customwas collected (5 h)
  2. filtrationThe mixture was filtered
  3. concentrationconcentrated to an oily brown residue
  4. dissolutionThe residue was dissolved in 25 mL of anhydrous MeOH
  5. additionTo this mixture was added S(0) (2.40 g)
  6. temperatureThe mixture was cooled in and ice bath
  7. filtrationFiltered the material
  8. washwashed with cold MeOH
  9. customto give 10.04 g
  10. custom, 3.64 g, was collected

Sources & evidence

ORD record
ord-d2f723c8ef1d4596a4cbe5141e5a7ce5
Source dataset
uspto-grants-2012_01
Patent number
US08093266B2

Reaction notes

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