Tetrahydrofuran → HCID 71272190, compound

HRID 475151Notes

Reaction equation

HRID 475151 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]#[N:13])[C:5]2[C:6](I)=[N:7][NH:8][C:9]=2[CH:10]=1.[O:14]1[CH:19]=[CH:18][CH2:17][CH2:16][CH2:15]1.[CH2:20]1COCC1>>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]#[N:13])[C:5]2[C:6]([CH3:20])=[N:7][N:8]([CH:19]3[CH2:18][CH2:17][CH2:16][CH2:15][O:14]3)[C:9]=2[CH:10]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 80803,4-dihydro-2H-pyranHCID 178509895HCID 178509895, compound

Product 1

HCID 71272190HCID 71272190, compoundYield 78.4%

Conditions

Temperature
80 °C

Procedure

A mixture of 6-chloro-3-iodo-1H-indazole-4-carbonitrile (2.0 g, 6.59 mmol), dihydropyran (1.09 g, 13.18 mmol), and TsOH monohydrate (127 mg, 0.659 mmol) in THF (40 mL) under nitrogen was heated at 80° C. overnight. The reaction mixture was quenched with water (40 mL) and extracted with EtOAc (50 mL×3). The combined extracts were washed with brine, dried (MgSO4), filtered, and concentrated in vacuo. The residue was purified by SiO2 chromatography eluting with petroleum ether/EtOAc (5:1) to afford 6-chloro-3-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-4-carbonitrile as white solid (2 g, 78.4%). MS (ESI): m/z=388 [M+1]+.

Workup

  1. customThe reaction mixture was quenched with water (40 mL)
  2. extractionextracted with EtOAc (50 mL×3)
  3. washThe combined extracts were washed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by SiO2 chromatography
  8. washeluting with petroleum ether/EtOAc (5:1)

Sources & evidence

ORD record
ord-ed7f39dc97e4480692fc6f8dd4f74e4e
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

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