3,4-dihydro-2H-pyran → 5-(Bromomethyl)-1-(2-tetrahydropyranyl)indazole

HRID 1263433Notes

Reaction equation

HRID 1263433 reaction equation
Br.[Br:2][CH2:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][N:8]=[CH:7]2.[O:13]1[CH:18]=[CH:17][CH2:16][CH2:15][CH2:14]1>C1COCC1.C(Cl)Cl>[Br:2][CH2:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH:14]1[CH2:15][CH2:16][CH2:17][CH2:18][O:13]1)[N:8]=[CH:7]2

Participants

5

Reactant 2

HCID 80803,4-dihydro-2H-pyranHCID 226614415-(Bromomethyl)-1H-indazole--hydrogen bromide (1/1)2×

Product 1

HCID 105657815-(Bromomethyl)-1-(2-tetrahydropyranyl)indazoleYield 80.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A yellow suspension of 5-(bromomethyl)-1H-indazole hydrogen bromide (compound 92, 3.0 g, 14 mmol) and 3,4-dihydro-2H-pyran (Aldrich, 2.4 g, 29 mmol) in THF (100 mL) was heated at reflux temperature for 2 hours. After cooling down to room temperature, the reaction mixture was stirred at room temperature for 12 hours under nitrogen. The reaction mixture was diluted with methylene chloride (250 mL), washed with saturated aqueous NaHCO3, water and brine. After drying (MgSO4), the solvent was removed under vacuum to give a yellow oil. Flash chromatography yielded the title compound (93, 3.34 g, 80%). TLC Rf 0.58 (70:30 hexane-ethyl acetate); MS (electrospray) 295, 297 (M+1); 1H N MR (CDCl3) δ1.57-1.84 (m, 3H), 2.16 (m, 2H), 2.55 (m, 1H), 3.75 (m, 1H), 4.01 (m, 1H), 4.65 (s, 2H), 5.71 (d, 1H, J=9.2 Hz), 7.44 (d, 1H, J=8.8 Hz), 7.59 (d, 1H, J=8.8 Hz), 7.73 (s, 1H), 8.00 (s, 1H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux temperature for 2 hours
  3. washwashed with saturated aqueous NaHCO3, water and brine
  4. dry with materialAfter drying (MgSO4)
  5. customthe solvent was removed under vacuum
  6. customto give a yellow oil

Sources & evidence

ORD record
ord-579fe2a8e9764bc291f31210c5fa0e5b
Source dataset
uspto-grants-2003_04
Patent number
US06541467B1

Reaction notes

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