Di-tert-butyl dicarbonate → 6-(2,4-Difluorophenoxy)-3-iodo-4-methyl-5-oxo-4,5-dihydro-pyrazolo[4,3-b]pyridine-1-carboxylic acid tert-butyl ester

HRID 230178Notes

Reaction equation

HRID 230178 reaction equation
[F:1][C:2]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:3]=1[O:4][C:5]1[C:10](=[O:11])[N:9]([CH3:12])[C:8]2[C:13]([I:16])=[N:14][NH:15][C:7]=2[CH:6]=1.[O:22](C(OC(C)(C)C)=O)[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=O>O1CCCC1.CN(C1C=CN=CC=1)C.C(OCC)(=O)C.O>[C:26]([O:25][C:23]([N:15]1[C:7]2[CH:6]=[C:5]([O:4][C:3]3[CH:17]=[CH:18][C:19]([F:21])=[CH:20][C:2]=3[F:1])[C:10](=[O:11])[N:9]([CH3:12])[C:8]=2[C:13]([I:16])=[N:14]1)=[O:22])([CH3:29])([CH3:28])[CH3:27]

Participants

7

Reactant 2

HCID 90495Di-tert-butyl dicarbonateHCID 1784815796-(2,4-Difluorophenoxy)-3-iodo-4-methyl-1,4-dihydro-pyrazolo[4,3-b]pyridin-5-one

Product 1

HCID 598128286-(2,4-Difluorophenoxy)-3-iodo-4-methyl-5-oxo-4,5-dihydro-pyrazolo[4,3-b]pyridine-1-carboxylic acid tert-butyl esterYield 120%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 6-(2,4-difluorophenoxy)-3-iodo-4-methyl-1,4-dihydro-pyrazolo[4,3-b]pyridin-5-one (12 mg, 0.0298 mmol) in tetrahydrofuran (5 mL) was added BOC2O (16 mg, 2.5 eq) and DMAP (catalytic). The resulting mixture was heated under reflux for 30 minutes, cooled to room temperature, and diluted with ethyl acetate (35 mL) and water (25 mL). The organic layer was separated, washed successively with water (2×25 mL), 0.5 N HCl (2×20 mL) and brine (1×25 mL), dried over magnesium sulfate, filtered and concentrated to give the title compound as a white powder (18 mg, (M+H)+=504).

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureunder reflux for 30 minutes
  3. customThe organic layer was separated
  4. washwashed successively with water (2×25 mL), 0.5 N HCl (2×20 mL) and brine (1×25 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-7e320f45914346ce90b53cd70ef28ac9
Source dataset
uspto-grants-2009_07
Patent number
US07566708B2

Reaction notes

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