3,4-dihydro-2H-pyran → 3-Bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carbonitrile

HRID 2183152Notes

Reaction equation

HRID 2183152 reaction equation
[Br:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]#[N:12])[CH:9]=2)[NH:4][N:3]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[O:25]1[CH:30]=[CH:29][CH2:28][CH2:27][CH2:26]1>O1CCCC1>[Br:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]#[N:12])[CH:9]=2)[N:4]([CH:26]2[CH2:27][CH2:28][CH2:29][CH2:30][O:25]2)[N:3]=1

Participants

5

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 521998p-Toluenesulfonic acid monohydrateHCID 178509531HCID 178509531, compound

Product 1

HCID 224799453-Bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carbonitrileYield 76.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 13.67 g (61.56 mmol) of 3-bromo-1H-indazole-5-carbonitrile and 2.06 g (10.8 mmol, 0.175 equiv.) of p-toluenesulfonic acid monohydrate in 247 mL of anhydrous tetrahydrofuran (THF) was added 11.2 mL (123 mmol, 2.00 equiv.) of 3,4-dihydro-2H-pyran. The mixture was refluxed under a nitrogen atmosphere for 14 h. The reaction was quenched with saturated aqueous sodium bicarbonate (sat. aq. NaHCO3). The mixture was extracted twice with EtOAc. The combined organics were washed with 2× sat. aq. NaHCO3, 1× sat. aq. NaCl, and dried over Na2SO4. Chromatography of the crude material on 200 g of silica gel using 30% EtOAc in hexanes afforded the title compound (14.34 g, 76% yield): ES-MS (m/z) 306 [M+1]+.

Workup

  1. temperatureThe mixture was refluxed under a nitrogen atmosphere for 14 h
  2. customThe reaction was quenched with saturated aqueous sodium bicarbonate (sat. aq. NaHCO3)
  3. extractionThe mixture was extracted twice with EtOAc
  4. washThe combined organics were washed with 2× sat. aq. NaHCO3, 1× sat. aq. NaCl
  5. dry with materialdried over Na2SO4

Sources & evidence

ORD record
ord-e466b6501f61434c95f2db1948ab5ab3
Source dataset
uspto-grants-2005_05
Patent number
US06897231B2

Reaction notes

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