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

HRID 1634072Notes

Reaction equation

HRID 1634072 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) (5) and 3,4-dihydro-2H-pyran (7.2 g, 86 mmol) in THF (200 mL) was heated at reflux for 2 hours. The reaction mixture was additionally 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) δ 1.57-1.84 (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 for 2 hours
  3. washwashed with saturated 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-48430ce134a348cfbd1ef2461947f27d
Source dataset
uspto-grants-2003_01
Patent number
US06506754B1

Reaction notes

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