3,4-dihydro-2H-pyran → 5-bromo-1-(oxan-2-yl)-1H-indazole

HRID 1057098Notes

Reaction equation

HRID 1057098 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[CH:5]2.[O:11]1[CH:16]=[CH:15][CH2:14][CH2:13][CH2:12]1.CC1C=CC(S([O-])(=O)=O)=CC=1.C1C=C[NH+]=CC=1>ClCCl>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:12]1[CH2:13][CH2:14][CH2:15][CH2:16][O:11]1)[N:6]=[CH:5]2

Participants

5

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 7619295-bromo-1H-indazole

Product 1

HCID 534338265-bromo-1-(oxan-2-yl)-1H-indazoleYield 91.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A 250-mL round-bottom flask equipped with a magnetic stir bar, a rubber septum, and a N2 inlet was charged with 5-bromo-1H-indazole (10 g, 50.7 mmol) and anhydrous dichloromethane (101 mL). To this solution, 3,4-dihydro-2H-pyran (23 mL, 253.8 mmol) was added in one portion at room temperature followed by addition of PPTS (1.28 g, 5 mmol). The resulting mixture was stirred at room temperature for 48 h. Upon completion by TLC, the reaction mixture was quenched with water and extracted with dichloromethane (3×100 mL). The combined organic extracts were washed with water (100 mL), washed with brine (50 mL), dried over sodium sulfate, filtered, concentrated, and purified by silica gel chromatography (0-10% ethyl acetate in hexanes) to give the title compound (13 g) as a pale yellow oil. 1H NMR (300 MHz, DMSO-d6): δ 8.10 (s, 1H), 8.02 (d, 1H), 7.73 (d, 1H), 7.53 (dd, 1H), 5.86 (dd, 1H), 3.89-3.85 (m, 1H), 3.73-3.69 (m, 1H), 2.43-2.31 (m, 1H), 2.06-1.92 (m, 2H), 1.80-1.64 (m, 1H), 1.60-150 (m, 2H).

Workup

  1. customA 250-mL round-bottom flask equipped with a magnetic stir bar
  2. customUpon completion by TLC, the reaction mixture was quenched with water
  3. extractionextracted with dichloromethane (3×100 mL)
  4. washThe combined organic extracts were washed with water (100 mL)
  5. washwashed with brine (50 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified by silica gel chromatography (0-10% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-566ac810d3b048c18c8666c60fddd395
Source dataset
uspto-grants-2016_07
Patent number
US09399646B2

Reaction notes

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