N-bromobutanimide → N-[2-(3-Bromo-6-chloro-2H-indazol-2-yl)-1-cyano-1-methylethyl]-4-trifluoromethoxybenzamide

HRID 70994Notes

Reaction equation

HRID 70994 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[C:9]([CH:10]=1)=[N:8][N:7]([CH2:11][C:12]([NH:16][C:17](=[O:29])[C:18]1[CH:23]=[CH:22][C:21]([O:24][C:25]([F:28])([F:27])[F:26])=[CH:20][CH:19]=1)([C:14]#[N:15])[CH3:13])[CH:6]=2.[Br:30]N1C(=O)CCC1=O>C(#N)C.O>[Br:30][C:6]1[N:7]([CH2:11][C:12]([NH:16][C:17](=[O:29])[C:18]2[CH:23]=[CH:22][C:21]([O:24][C:25]([F:26])([F:27])[F:28])=[CH:20][CH:19]=2)([C:14]#[N:15])[CH3:13])[N:8]=[C:9]2[C:5]=1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:10]2

Participants

5

Reactant 2

HCID 67184N-bromobutanimideHCID 66620249N-[2-(6-chloro-2H-indazol-2-yl)-1-cyano-1-methylethyl]-4-trifluoromethoxybenzamide

Product 1

HCID 66620620N-[2-(3-Bromo-6-chloro-2H-indazol-2-yl)-1-cyano-1-methylethyl]-4-trifluoromethoxybenzamideYield 44.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of N-[2-(6-chloro-2H-indazol-2-yl)-1-cyano-1-methylethyl]-4-trifluoromethoxybenzamide (25 mg, described in Example 132), and N-bromosuccinimide (10 mg) in acetonitrile (1 mL) was heated to 60° C. for 3.5 hours. The mixture was cooled to room temperature, diluted with water and extracted with ethyl acetate. The organic layer was collected, dried over sodium sulfate, filtered and concentrated under reduced pressure to give a residue that was purified by chromatography (SiO2, heptane/EA) to afford the title compound (12.5 mg, 42%). MS (ES): M/Z [M+H]=501. 1H NMR: (400 MHz, CHLOROFORM-d): 1.90 (s, 3H), 4.82 (d, J=14.3 Hz, 1H), 5.05 (d, J=14.3 Hz, 1H), 7.14 (dd, J=9.0, 1.6 Hz, 1H), 7.34 (d, J=8.2 Hz, 2H), 7.50 (d, J=8.9 Hz, 1H), 7.63 (d, J=0.9 Hz, 1H), 7.93 (d, J=8.8 Hz, 2H) and 8.71 (s, 1H). 19F NMR (376 MHz, CHLOROFORM-d): −58.1 (s, 3F).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionextracted with ethyl acetate
  3. customThe organic layer was collected
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give a residue that
  8. customwas purified by chromatography (SiO2, heptane/EA)

Sources & evidence

ORD record
ord-cbdf1b65a0b34837b339ffecfdc93c0c
Source dataset
uspto-grants-2014_09
Patent number
US08822689B2

Reaction notes

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