Chlorosuccinimide → ethyl 3-((2,6-dichloro-1-(1-propyl-1H-pyrazol-4-yl)-1H-indol-3-yl)thio)benzoate

HRID 522752Notes

Reaction equation

HRID 522752 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[N:23]([C:32]2[CH:33]=[N:34][N:35]([CH2:37][CH2:38][CH3:39])[CH:36]=2)[C:24]2[C:29]([CH:30]=1)=[CH:28][CH:27]=[C:26]([Cl:31])[CH:25]=2>C(Cl)Cl.O>[Cl:21][C:22]1[N:23]([C:32]2[CH:33]=[N:34][N:35]([CH2:37][CH2:38][CH3:39])[CH:36]=2)[C:24]2[C:29]([C:30]=1[S: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])=[CH:28][CH:27]=[C:26]([Cl:31])[CH:25]=2

Participants

6

Reactant 3

HCID 31398ChlorosuccinimideHCID 13213120Ethyl 3-sulfanylbenzoateHCID 1181041872,6-dichloro-1-(1-propyl-1H-pyrazol-4-yl)-1H-indole

Product 1

HCID 118104189ethyl 3-((2,6-dichloro-1-(1-propyl-1H-pyrazol-4-yl)-1H-indol-3-yl)thio)benzoateYield 5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of ethyl 3-mercaptobenzoate (124.9 mg, 0.68 mmol) in CH2Cl2 (20 mL) under inert atmosphere was added NCS (109 mg, 0.81 mmol) at 0° C.; warmed to RT and stirred for 1 h. To this, compound 3 (200 mg, 0.68 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 (25 mL) and extracted with CH2Cl2 (3×25 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated under reduced pressure to obtain the crude. This was purified by preparative HPLC to afford compound 4 (15 mg, 5%) as colorless oil. 1H NMR (500 MHz, CDCl3): δ 7.90 (s, 1H), 7.79-7.77 (m, 1H), 7.69 (s, 1H), 7.66 (s, 1H), 7.48 (d, J=9.0 Hz, 1H), 7.26-7.22 (m, 3H), 7.16 (d, J=9.0 Hz, 1H), 4.32 (q, J=7.5 Hz, 2H), 4.20 (t, J=7.0 Hz, 2H), 2.02-1.98 (m, 2H), 1.37-1.34 (t, J=7.5 Hz, 3H), 1.01 (t, J=7.0 Hz, 3H); LC-MS (ESI): 92.7%; m/z 475.8 (M+H+); (column: X Select C-18, 50×3.0 mm, 3.5 μm); RT 5.03 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 (3×25 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 preparative HPLC

Sources & evidence

ORD record
ord-465c35f8d13f4ad5a8c22e2f2dd5a170
Source dataset
uspto-grants-2016_05
Patent number
US09334261B2

Reaction notes

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