N-bromobutanimide → ethyl 3-((2-bromo-6-chloro-1-(1-ethyl-1H-pyrazol-4-yl)-7-fluoro-1H-indol-3-yl)thio)-2-fluorobenzoate

HRID 2171298Notes

Reaction equation

HRID 2171298 reaction equation
[Cl:1][C:2]1[C:10]([F:11])=[C:9]2[C:5]([C:6]([S:19][C:20]3[C:21]([F:31])=[C:22]([CH:28]=[CH:29][CH:30]=3)[C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:7][N:8]2[C:12]2[CH:13]=[N:14][N:15]([CH2:17][CH3:18])[CH:16]=2)=[CH:4][CH:3]=1.C1C(=O)N([Br:39])C(=O)C1>C(Cl)(Cl)(Cl)Cl.O>[Br:39][C:7]1[N:8]([C:12]2[CH:13]=[N:14][N:15]([CH2:17][CH3:18])[CH:16]=2)[C:9]2[C:5]([C:6]=1[S:19][C:20]1[C:21]([F:31])=[C:22]([CH:28]=[CH:29][CH:30]=1)[C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:4][CH:3]=[C:2]([Cl:1])[C:10]=2[F:11]

Participants

5

Reactant 2

HCID 67184N-bromobutanimideHCID 118094256ethyl 3-((6-chloro-1-(1-ethyl-1H-pyrazol-4-yl)-7-fluoro-1H-indol-3-yl)thio)-2-fluorobenzoate

Product 1

HCID 118094246ethyl 3-((2-bromo-6-chloro-1-(1-ethyl-1H-pyrazol-4-yl)-7-fluoro-1H-indol-3-yl)thio)-2-fluorobenzoateYield 77.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 5943Carbon TetrachlorideSolvent

Procedure

To a stirred solution of compound 10 (200 mg, 0.43 mmol) in CCl4 (10 mL) under inert atmosphere was added NBS (178 mg, 0.99 mmol) at RT and stirred for 16 h. After completion of the reaction by TLC, the reaction mixture was diluted with water (10 mL) and extracted with CH2Cl2 (2×20 mL). The combined organic extracts were washed with brine (10 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to obtain the crude. The crude was purified (silica gel chromatography; 5-7% EtOAc/Hexanes) to afford compound 11 (180 mg, 77%) as an off-white solid. 1H NMR (500 MHz, CDCl3): δ 7.70-7.67 (m, 1H), 7.65 (s, 2H), 7.30 (d, J=8.0 Hz, 1H), 7.17 (dd, J=8.5, 6.0 Hz, 1H), 7.00-6.98 (m, 2H), 4.40 (q, J=7.5 Hz, 2H), 4.27 (q, J=7.5 Hz, 2H), 1.58 (t, J=7.5 Hz, 3H), 1.40 (t, J=7.5 Hz, 3H); LC-MS (ESI): 99.5%; m/z 542.4 (M++2); (column: X Select CSH C-18, 50×3.0 mm, 3.5 μm); RT 4.80 min; 5 mM NH4OAc: ACN; 0.8 mL/min).

Workup

  1. customAfter completion of the reaction by TLC
  2. extractionextracted with CH2Cl2 (2×20 mL)
  3. washThe combined organic extracts were washed with brine (10 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto obtain the crude
  8. customThe crude was purified (silica gel chromatography; 5-7% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-9bb3881ff3384f9eb70305118fb06211
Source dataset
uspto-grants-2015_06
Patent number
US09051320B1

Reaction notes

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