Potassium Carbonate → Methyl 4-(benzyloxy)-6-chloropyrazolo[1,5-a]pyridine-3-carboxylate

HRID 2209247Notes

Reaction equation

HRID 2209247 reaction equation
CC1C=C(C)C=C(C)C=1S([O-])(=O)=O.[NH2:14][N+:15]1[CH:20]=[C:19]([Cl:21])[CH:18]=[C:17]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:16]=1.C([O-])([O-])=O.[K+].[K+].[C:36]([O:40][CH3:41])(=[O:39])[C:37]#[CH:38].C([O-])(O)=O.[Na+]>CN(C=O)C.CCOC(C)=O>[CH2:23]([O:22][C:17]1[C:16]2[N:15]([N:14]=[CH:38][C:37]=2[C:36]([O:40][CH3:41])=[O:39])[CH:20]=[C:19]([Cl:21])[CH:18]=1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 13536Methyl propiolateHCID 516892Sodium BicarbonateHCID 1178429311-Amino-3-(benzyloxy)-5-chloropyridin-1-ium 2,4,6-trimethylbenzenesulfonate

Product 1

HCID 117843167Methyl 4-(benzyloxy)-6-chloropyrazolo[1,5-a]pyridine-3-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1-amino-3-(benzyloxy)-5-chloropyridin-1-ium 2,4,6-trimethylbenzenesulfonate (2.18 g, 5.01 mmol) in DMF (50.0 mL) was added K2CO3 (1.73 g, 12.5 mmol) and the reaction was stirred for 5 minutes. Methyl propiolate (2.11 g, 25.1 mmol) was added and the reaction was stirred overnight open to air to afford a mixture of diastereomers. EtOAc and a saturated aqueous solution of NaHCO3 were added, the layers were separated and the organic layer was washed with brine, dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography (5-20% EtOAc in hexanes) to afford methyl 4-(benzyloxy)-6-chloropyrazolo[1,5-a]pyridine-3-carboxylate, which was the first eluting diastereomer.

Workup

  1. stirringthe reaction was stirred overnight open to air
  2. customto afford
  3. additiona mixture of diastereomers
  4. customthe layers were separated
  5. washthe organic layer was washed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash chromatography (5-20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-ae29043d7e4d48c4b580db1535072b24
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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