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

HRID 254002Notes

Reaction equation

HRID 254002 reaction equation
O=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.BrBr.[NH2:17][C:18]([NH2:20])=[S:19].C([O-])([O-])=O.[Na+].[Na+]>C(Cl)(Cl)Cl.CCCCC>[NH2:20][C:18]1[S:19][C:3]2[CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7][C:2]=2[N:17]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 24408BromineHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 2723790Thiourea

Product 1

HCID 11357283tert-butyl 2-amino-4H,5H,6H,7H-[1,3]thiazolo[5,4-c]pyridine-5-carboxylateYield 47.3%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolvent2×HCID 8003PentaneSolvent

Procedure

To a solution of compound tert-butyl 4-oxopiperidine-1-carboxylate (24.0 g, 120.6 mmol) in dry CHCl3 (500 mL) at 0-5° C., was slowly added a solution of Br2 in CHCl3 (100 mL) over 1.5 hours. The reaction mixture was warmed to RT and stirred for 3 hours. The reaction mixture was concentrated to obtain solid, which was thoroughly washed with Et2O. The resulting intermediate tert-butyl 3-bromo-4-oxopiperidine-1-carboxylate was used immediately in the next reaction. Accordingly, this intermediate (20 g, 72 mmol) was suspended in pentane, filtered, washed with pentane, and the solid so obtained dried in vacuo and dissolved in EtOH (100 mL). Thiourea (5.46 g, 72.0 mmol) was added and the reaction mixture heated for 4 hours at 70-75° C. The reaction mixture was concentrated to yield a residue, which was treated with aq. Na2CO3 solution, adjusted to pH=10, extracted with EtOAc, washed with water, washed with brine solution, dried (Na2SO4), filtered, and concentrated. The residue washed with pentane to obtain tert-butyl 2-amino-6,7-dihydrothiazolo[5,4-c]pyridine-5(4H)-carboxylate (8.7 g, 28% yield)

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customto obtain solid, which
  3. washwas thoroughly washed with Et2O
  4. customThe resulting intermediate tert-butyl 3-bromo-4-oxopiperidine-1-carboxylate was used immediately in the next reaction
  5. filtrationfiltered
  6. washwashed with pentane
  7. customthe solid so obtained
  8. customdried in vacuo
  9. dissolutiondissolved in EtOH (100 mL)
  10. temperaturethe reaction mixture heated for 4 hours at 70-75° C
  11. concentrationThe reaction mixture was concentrated
  12. customto yield a residue, which
  13. extractionextracted with EtOAc
  14. washwashed with water
  15. washwashed with brine solution
  16. dry with materialdried (Na2SO4)
  17. filtrationfiltered
  18. concentrationconcentrated
  19. washThe residue washed with pentane

Sources & evidence

ORD record
ord-04ae2928eaa949479b86323638db15ab
Source dataset
uspto-grants-2011_01
Patent number
US07872031B2

Reaction notes

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