Chlorosuccinimide → ethyl 3-((6-chloro-7-fluoro-1-(1-propyl-1H-pyrazol-4-yl)-1H-indol-3-yl) thio)benzoate

HRID 522759Notes

Reaction equation

HRID 522759 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[C:30]([F:31])=[C:29]2[C:25]([CH:26]=[CH:27][N:28]2[C:32]2[CH:33]=[N:34][N:35]([CH2:37][CH2:38][CH3:39])[CH:36]=2)=[CH:24][CH:23]=1>C(Cl)Cl.O>[Cl:21][C:22]1[C:30]([F:31])=[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:32]2[CH:33]=[N:34][N:35]([CH2:37][CH2:38][CH3:39])[CH:36]=2)=[CH:24][CH:23]=1

Participants

6

Reactant 3

HCID 31398ChlorosuccinimideHCID 13213120Ethyl 3-sulfanylbenzoateHCID 1181042006-chloro-7-fluoro-1-(1-propyl-1H-pyrazol-4-yl)-1H-indole

Product 1

HCID 118094259ethyl 3-((6-chloro-7-fluoro-1-(1-propyl-1H-pyrazol-4-yl)-1H-indol-3-yl) thio)benzoateYield 61%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of ethyl 3-mercaptobenzoate (66 mg, 0.36 mmol) in CH2Cl2 (5 mL) under inert atmosphere was added NCS (48.2 mg, 0.36 mmol) at RT and stirred for 50 min. To this, compound 3 (100 mg, 0.36 mmol) was added at RT and stirred for 16 h. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was diluted with water (25 mL) and extracted with CH2Cl2 (2×20 mL). The combined organic extracts were washed with brine (20 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to obtain the crude. This was purified by silica gel column chromatography using 9% EtOAc/Hexanes to afford compound 4 (100 mg, 61%) as a colorless syrup. 1H NMR (500 MHz, CDCl3): δ 7.88 (s, 1H), 7.77-7.76 (m, 1H), 7.69 (s, 1H), 7.67 (s, 1H), 7.43 (s, 1H), 7.27-7.24 (m, 3H), 7.15-7.12 (m, 1H), 4.33 (q, J=7.5 Hz, 2H), 4.15 (t, J=7.0 Hz, 2H), 1.98-1.94 (m, 2H), 1.35 (t, J=7.5 Hz, 3H), 0.98 (t, J=7.0 Hz, 3H); LC-MS: 94.6%; m/z 458.4 (M+H+); (column: X Select CSH C-18, 50×3.0 mm, 3.5 μm); RT 4.91 min; 5 mM NH4OAc: ACN; 0.8 mL/min).

Workup

  1. stirringstirred for 16 h
  2. customafter completion of the reaction
  3. extractionextracted with CH2Cl2 (2×20 mL)
  4. washThe combined organic extracts were washed with brine (20 mL)
  5. dry with materialdried 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-f8281e88e59f4c14ad8bac8d8a75cc06
Source dataset
uspto-grants-2016_05
Patent number
US09334261B2

Reaction notes

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