Water → 7-[(2,6-Difluorobenzyl)oxy]-2-methylpyrazolo[1,5-a]pyridine-3-carboxylic Acid ethyl Ester

HRID 1486295Notes

Reaction equation

HRID 1486295 reaction equation
CC1C=C(C)C=C(C)C=1S([O-])(=O)=O.[NH2:14][N+:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[O:21][CH2:22][C:23]1[C:28]([F:29])=[CH:27][CH:26]=[CH:25][C:24]=1[F:30].[C:31]([O:36][CH2:37][CH3:38])(=[O:35])[C:32]#[C:33][CH3:34].C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[CH2:37]([O:36][C:31]([C:32]1[C:33]([CH3:34])=[N:14][N:15]2[C:16]([O:21][CH2:22][C:23]3[C:28]([F:29])=[CH:27][CH:26]=[CH:25][C:24]=3[F:30])=[CH:17][CH:18]=[CH:19][C:20]=12)=[O:35])[CH3:38]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 78043Ethyl 2-butynoateHCID 1178586111-Amino-2-[(2,6-difluorobenzyl)oxy]pyridinium 2,4,6-trimethylbenzenesulphonate

Product 1

HCID 1178646217-[(2,6-Difluorobenzyl)oxy]-2-methylpyrazolo[1,5-a]pyridine-3-carboxylic Acid ethyl Ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A stirred solution of 540 mg (1.00 mmol, 81% pure) of 1-amino-2-[(2,6-difluorobenzyl)oxy]pyridinium-2,4,6-trimethylbenzenesulphonate from Example 128A in DMF (10 ml) at 0° C. was admixed with 0.35 ml (3.06 mmol) of ethyl 2-butynoate and 623 mg (4.51 mmol) of potassium carbonate. The reaction mixture was stirred at room temperature overnight and added dropwise to 20 ml of water while stirring. The resulting suspension was extracted with ethyl acetate (2×20 ml). The combined organic phases were dried with a phase separation cartridge and concentrated under reduced pressure. The residue was purified by flash chromatography using a prepacked silica gel cartridge (eluent:cyclohexane-ethyl acetate 10:1 to 1:1), which gave 200 mg (25% of theory, 43% pure) of the target compound.

Workup

  1. customat 0° C.
  2. stirringwhile stirring
  3. extractionThe resulting suspension was extracted with ethyl acetate (2×20 ml)
  4. customThe combined organic phases were dried with a phase separation cartridge
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash chromatography
  7. customgave 200 mg (25% of theory, 43% pure) of the target compound

Sources & evidence

ORD record
ord-10f7b0f8bfd547d782a709895aaf7590
Source dataset
uspto-grants-2016_08
Patent number
US09422285B2

Reaction notes

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