Chlorosuccinimide → ethyl 3-((6-chloro-1-(1-propyl-1H-pyrazol-4-yl)-1H-indol-3-yl)thio)benzoate

HRID 522754Notes

Reaction equation

HRID 522754 reaction equation
[SH:1][C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][CH:12]=1)[C:5]([O:7][CH2:8][CH3:9])=[O:6].C1C(=O)N(Cl)C(=O)C1.[Cl:21][C:22]1[CH:30]=[C:29]2[C:25]([CH:26]=[CH:27][N:28]2[C:31]2[CH:32]=[N:33][N:34]([CH2:36][CH2:37][CH3:38])[CH:35]=2)=[CH:24][CH:23]=1>C(Cl)Cl.O>[Cl:21][C:22]1[CH:30]=[C:29]2[C:25]([C:26]([S:1][C:2]3[CH:3]=[C:4]([CH:10]=[CH:11][CH:12]=3)[C:5]([O:7][CH2:8][CH3:9])=[O:6])=[CH:27][N:28]2[C:31]2[CH:32]=[N:33][N:34]([CH2:36][CH2:37][CH3:38])[CH:35]=2)=[CH:24][CH:23]=1

Participants

6

Reactant 3

HCID 31398ChlorosuccinimideHCID 13213120Ethyl 3-sulfanylbenzoateHCID 1180942196-chloro-1-(1-propyl-1H-pyrazol-4-yl)-1H-indole

Product 1

HCID 118874672ethyl 3-((6-chloro-1-(1-propyl-1H-pyrazol-4-yl)-1H-indol-3-yl)thio)benzoateYield 83%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of ethyl 3-mercaptobenzoate (372 mg, 2.03 mmol) in CH2Cl2 (20 mL) under inert atmosphere was added NCS (271 mg, 2.03 mmol) at 0° C.; warmed to RT and stirred for 45 min. To this, compound 2 (500 mg, 1.93 mmol) was added at 0° C.; warmed to RT and stirred for 12 h. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was diluted with water (40 mL) and extracted with CH2Cl2 (3×20 mL). The combined organic extracts were dried over Na2SO4, 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 3 (700 mg, 83%) as a yellow oil. 1H NMR (400 MHz, CDCl3): δ 7.89 (s, 1H), 7.76-7.74 (m, 1H), 7.72 (s, 1H), 7.68 (s, 1H), 7.49-7.47 (m, 2H), 7.40 (s, 1H), 7.24-7.23 (m, 2H), 7.15 (d, J=8.4 Hz, 1H), 4.32 (q, J=7.2 Hz, 2H), 4.18 (t, J=7.2 Hz, 2H), 2.01-1.96 (m, 2H), 1.34 (t, J=7.2 Hz, 3H), 1.00 (t, J=7.2 Hz, 3H); LC-MS (ESI): 72.2%; m/z 440.4 (M+H+); (column: X Select CSH C-18, 50×3.0 mm, 3.5 μm); RT 4.87 min; 5 mM NH4OAc: ACN; 0.8 mL/min).

Workup

  1. temperaturewarmed to RT
  2. stirringstirred for 12 h
  3. customafter completion of the reaction
  4. extractionextracted with CH2Cl2 (3×20 mL)
  5. dry with materialThe combined organic extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto obtain the crude
  9. customThis was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-49347710e3564f208c6bfa93003f8dfb
Source dataset
uspto-grants-2016_05
Patent number
US09334261B2

Reaction notes

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