3,4-dihydro-2H-pyran → 6-(Bromomethyl)-1-(tetrahydro-2H-pyran-2-YL)-1H-indazole

HRID 1263439Notes

Reaction equation

HRID 1263439 reaction equation
Br.[Br:2][CH2:3][C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[N:9][NH:10]2)=[CH:6][CH:5]=1.[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:12]=[C:11]2[C:7]([CH:8]=[N:9][N:10]2[CH:14]2[CH2:15][CH2:16][CH2:17][CH2:18][O:13]2)=[CH:6][CH:5]=1

Participants

5

Reactant 2

HCID 80803,4-dihydro-2H-pyranHCID 513419766-(Bromomethyl)-1H-indazole hydrobromide

Product 1

HCID 186161856-(Bromomethyl)-1-(tetrahydro-2H-pyran-2-YL)-1H-indazoleYield 72%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A yellow-suspension of 6-(bromomethyl)-1H-indazole hydrogen bromide (9.0 g, 43 mmol) (99) and 3,4-dihydro-2H-pyran (7.2 g, 86 mmol) in THF (200 mL) was heated at its 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 solution was diluted with methylene chloride (500 mL), washed with saturated NaHCO3, water and brine. After drying (MgSO4) the solvent was removed under vacuum to give a yellow oil. Flash chromatography yielded the title compound (6.6 g, 72%). TLC Rf 0.52 (80:20 of 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 at its
  2. temperaturereflux temperature for 2 hours
  3. washwashed with saturated NaHCO3, water and brine
  4. dry with materialAfter drying (MgSO4) the solvent
  5. customwas removed under vacuum
  6. customto give a yellow oil

Sources & evidence

ORD record
ord-def27c6950214049823e76ac5b850171
Source dataset
uspto-grants-2003_04
Patent number
US06541467B1

Reaction notes

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