Tetrahydrofuran → 5-Bromo-6-fluoro-1-methyl-1H-indazole

HRID 1942053Notes

Reaction equation

HRID 1942053 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][C:12]=1[F:13])[NH:9][N:8]=[CH:7]2.[CH2:14]1COCC1>>[Br:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][C:12]=1[F:13])[N:9]([CH3:14])[N:8]=[CH:7]2

Participants

4

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 24758Sodium hydrideHCID 468639235-Bromo-6-fluoro-1H-indazole

Product 1

HCID 579172745-Bromo-6-fluoro-1-methyl-1H-indazole

Procedure

To a suspension of NaH (8.84 g, 221 mmol) in THF (50 mL) was added dropwise a solution of 5-bromo-6-fluoro-1H-indazole (CAS 105391-70-6, 44.1 g, 201 mmol) in THF (200 mL) at 5° C. After 15 min at 5° C., Mel (31.7 mL, 221 mmol) was added at 5° C. and the RM was stirred between 0° C. and 5° C. for 1.5 h. The reaction was quenched with 0.5 M HCl and extracted with EtOAc. The organic phases were combined, washed with brine, dried over Na2SO4 and evaporated under vacuo. The 2 isomers formed were separated by MPLC with heptane and EtOAc to afford the title compound as a yellow solid (tR 5.07 min (conditions 1), NMR in DMSO-d6: 8.14 (d, 1H); 8.04 (s, 1H); 7.79 (d, 1H); 4.00 (s, 3H)).

Workup

  1. additionMel (31.7 mL, 221 mmol) was added at 5° C.
  2. customThe reaction was quenched with 0.5 M HCl
  3. extractionextracted with EtOAc
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. customevaporated under vacuo
  7. customThe 2 isomers formed
  8. customwere separated by MPLC with heptane and EtOAc

Sources & evidence

ORD record
ord-5e9bfbfa098a4d85864a361c47a2e2e7
Source dataset
uspto-grants-2013_03
Patent number
US08389526B2

Reaction notes

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