N-bromobutanimide → 4-(4-Bromo-2-fluorophenylamino)-indazole-1,5-dicarboxylic acid di-tert-butyl ester

HRID 79021Notes

Reaction equation

HRID 79021 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[C:12]([NH:24][C:25]3[CH:30]=[CH:29][C:28]([Si](C)(C)C)=[CH:27][C:26]=3[F:35])[C:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[CH:14][CH:15]=2)[CH:10]=[N:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br:36]N1C(=O)CCC1=O>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[C:12]([NH:24][C:25]3[CH:30]=[CH:29][C:28]([Br:36])=[CH:27][C:26]=3[F:35])[C:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[CH:14][CH:15]=2)[CH:10]=[N:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 67184N-bromobutanimideHCID 575231194-(2-Fluoro-4-trimethylsilanylphenylamino)-indazole-1,5-dicarboxylic acid di-tert-butyl ester

Product 1

HCID 670840354-(4-Bromo-2-fluorophenylamino)-indazole-1,5-dicarboxylic acid di-tert-butyl esterYield 92%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of 4-(2-fluoro-4-trimethylsilanyl-phenylamino)-indazole-1,5-dicarboxylic acid di-tert-butyl ester (850 mg, 1.7 mmol) in DCM (10 mL) at −15° C. was added N-bromosuccinimide (303 mg, 1.7 mmol) as a solution in DCM (3 mL) dropwise. The reaction mixture was stirred at −15° C. for 1.25 hours before DCM was added and the solution washed (saturated aqueous NaHCO3 then water), dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si—PPC, gradient 0 to 10% ethyl acetate in cyclohexane) to give the title compound as an orange gum (790 mg, 92%). LCMS (method B) RT=5.41 min, [M+CH3CN+Na]+=569/571.

Workup

  1. additionwas added
  2. washthe solution washed (saturated aqueous NaHCO3
  3. dry with materialwater), dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f9a1b6e2b9fb4e419281faed5e2b469b
Source dataset
uspto-grants-2014_09
Patent number
US08841462B2

Reaction notes

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