3,4-dihydro-2H-pyran → HCID 69803802, compound

HRID 1507113Notes

Reaction equation

HRID 1507113 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[C:5]2[C:11]([O:13][CH3:14])=[O:12].C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1.[O:32]1[CH:37]=[CH:36][CH2:35][CH2:34][CH2:33]1>ClC(Cl)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:33]1[CH2:34][CH2:35][CH2:36][CH2:37][O:32]1)[N:6]=[C:5]2[C:11]([O:13][CH3:14])=[O:12]

Participants

5

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 12689298Methyl 5-bromo-1H-indazole-3-carboxylate

Product 1

HCID 69803802HCID 69803802, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

A suspension of methyl 5-bromo-1H-indazole-3-carboxylate (CXVI) (1.35 g, 5.29 mmol), pyridinium p-toluenesulfonate (0.143 g, 0.56 mmol) and 3,4 dihydro-2H-pyran (1.02 mL, 11.90 mmol) in anhydrous dichloroethane (20 mL) was refluxed 5 h under argon. The suspension was turned into the clear solution. The solution was cooled and the excess solvent was evaporated under vacuum. The residue was dissolved in EtOAc and washed with dilute NaHCO3 solution (satd. NaHCO3 soln/H2O: 1:9). The organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography (100% hexanes→5:95 EtOAc:hexanes) to get methyl 5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carboxylate (CXVII) as a white solid (1.47 g, 4.34 mmol, 82% yield). 1H NMR (DMSO-d6) δ ppm 8.22 (d, J=1.4 Hz, 1H), 7.89 (d, J=7.2 Hz, 1H), 7.68 (dd, J=7.2, 1.6 Hz, 1H),), 6.02 (dd, J=8.0, 2.4 Hz, 1H), 3.94 (s, 3H), 3.88 (m, 1H), 3.79 (m, 1H), 2.37-2.31 (m, 1H), 2.05-1.96 (m, 2H), 1.77-1.73 (m, 1H). 1.60-1.58 (m, 2H); ESIMS found for C14H15BrN2O3 m/z 340.0 (M+H).

Workup

  1. temperaturewas refluxed 5 h under argon
  2. temperatureThe solution was cooled
  3. customthe excess solvent was evaporated under vacuum
  4. dissolutionThe residue was dissolved in EtOAc
  5. washwashed with dilute NaHCO3 solution (
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography (100% hexanes→5:95 EtOAc:hexanes)

Sources & evidence

ORD record
ord-70d503c3a4a34ac5a4cbca8c34286bc5
Source dataset
uspto-grants-2015_12
Patent number
US09221793B2

Reaction notes

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