N-bromobutanimide → ethyl 3-((2-bromo-6-chloro-1-(1-propyl-1H-pyrazol-4-yl)-1H-indol-3-yl)thio)benzoate

HRID 522755Notes

Reaction equation

HRID 522755 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([S:19][C:20]3[CH:21]=[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:11]2[CH:12]=[N:13][N:14]([CH2:16][CH2:17][CH3:18])[CH:15]=2)=[CH:4][CH:3]=1.C1C(=O)N([Br:38])C(=O)C1>C(Cl)(Cl)(Cl)Cl.O>[Br:38][C:7]1[N:8]([C:11]2[CH:12]=[N:13][N:14]([CH2:16][CH2:17][CH3:18])[CH:15]=2)[C:9]2[C:5]([C:6]=1[S:19][C:20]1[CH:21]=[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])[CH:10]=2

Participants

5

Reactant 2

HCID 67184N-bromobutanimideHCID 118874672ethyl 3-((6-chloro-1-(1-propyl-1H-pyrazol-4-yl)-1H-indol-3-yl)thio)benzoate

Product 1

HCID 118094237ethyl 3-((2-bromo-6-chloro-1-(1-propyl-1H-pyrazol-4-yl)-1H-indol-3-yl)thio)benzoateYield 48.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 5943Carbon TetrachlorideSolvent

Procedure

To a stirred solution of compound 3 (100 mg, 0.22 mmol) in CCl4 (10 mL) was added NBS (44.85 mg, 0.25 mmol) at RT under inert atmosphere and stirred for 12 h. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was diluted with water (20 mL) and extracted with CH2Cl2 (3×20 mL). The combined organic extracts were dried over sodium sulphate, filtered and concentrated under reduced pressure to obtain the crude. This was purified by silica gel column chromatography using 10-15% EtOAc/Hexanes to afford compound 4 (55 mg, 47%) as an off-white solid. 1H NMR (500 MHz, CDCl3): δ 7.90 (s, 1H), 7.78-7.77 (m, 1H), 7.68 (s, 1H), 7.66 (s, 1H), 7.49 (d, J=8.5 Hz, 1H), 7.25-7.24 (m, 2H), 7.20 (s, 1H), 7.14 (d, J=8.5 Hz, 1H), 4.35 (q, J=7.0 Hz, 2H), 4.20 (t, J=7.5 Hz, 2H), 2.03-1.98 (m, 2H), 1.35 (t, J=7.0 Hz, 3H), 1.01 (t, J=7.5 Hz, 3H); LC-MS (ESI): 93.3%; m/z 520.8 (M++2); (column: X Select CSH C-18, 50×3.0 mm, 3.5 μm); RT 5.02 min; 5 mM NH4OAc: ACN; 0.8 mL/min).

Workup

  1. customafter completion of the reaction
  2. extractionextracted with CH2Cl2 (3×20 mL)
  3. dry with materialThe combined organic extracts were dried over sodium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto obtain the crude
  7. customThis was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-b124c894e8144a2d968706eb4c0e3a8e
Source dataset
uspto-grants-2016_05
Patent number
US09334261B2

Reaction notes

Loading…