Water → 5-(2,6-difluoro-phenyl)-3-iodo-1-(tetrahydro-pyran-2-yl)-1H-indazole

HRID 1529279Notes

Reaction equation

HRID 1529279 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[C:12]2[I:18].[O:19]1[CH:24]=[CH:23][CH2:22][CH2:21][CH2:20]1.O>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH:20]1[CH2:21][CH2:22][CH2:23][CH2:24][O:19]1)[N:13]=[C:12]2[I:18]

Participants

5

Reactant 3

HCID 962WaterHCID 80803,4-dihydro-2H-pyranHCID 178505718HCID 178505718, compound

Product 1

HCID 679597535-(2,6-difluoro-phenyl)-3-iodo-1-(tetrahydro-pyran-2-yl)-1H-indazoleYield 78.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 5-(2,6-difluoro-phenyl)-3-iodo-1H-indazole (45.5 g, 127.76 mmol) and TSA (4.86 g, 25.55 mmol) in THF (383.2 mL) was added 3,4-dihydro-2H-pyran (23.8 mL, 255.53 mmol) at RT. The mixture was stirred at 70° C. for 8 h. The reaction mixture was cooled to RT. Water was added to the reaction mixture and extracted with EtOAc (2×500 mL). The organic layer was washed with brine and dried over Na2SO4. The organic layer was concentrated under reduced pressure. The crude product was purified by column using (100-200 mesh) silica with 0-5% EtOAc in hexane to provide 5-(2,6-difluoro-phenyl)-3-iodo-1-(tetrahydro-pyran-2-yl)-1H-indazole (42.95 g, 78.2% yield). MS (ESI, pos. ion) m/z: 441.1 (M+1).

Workup

  1. temperatureThe reaction mixture was cooled to RT
  2. extractionextracted with EtOAc (2×500 mL)
  3. washThe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationThe organic layer was concentrated under reduced pressure
  6. customThe crude product was purified by column

Sources & evidence

ORD record
ord-b67e2ca3b240416abe91b1a90617c2bb
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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