Chlorosuccinimide → ethyl 3-((6-chloro-7-fluoro-1H-indol-3-yl)thio)-2-fluorobenzoate

HRID 522791Notes

Reaction equation

HRID 522791 reaction equation
FC1C(S)=CC=CC=1C(OCC)=O.C1C(=O)N(Cl)C(=O)C1.[Cl:22][C:23]1[C:31]([F:32])=[C:30]2[C:26]([C:27]([S:47][C:48]3[CH:53]=[CH:52][CH:51]=[C:50]([C:54]([O:56][CH2:57][CH3:58])=[O:55])[C:49]=3[F:59])=[C:28](C3CC3)[N:29]2C2C=NN(CCCC(O)=O)C=2)=[CH:25][CH:24]=1>C(Cl)Cl.O>[Cl:22][C:23]1[C:31]([F:32])=[C:30]2[C:26]([C:27]([S:47][C:48]3[C:49]([F:59])=[C:50]([CH:51]=[CH:52][CH:53]=3)[C:54]([O:56][CH2:57][CH3:58])=[O:55])=[CH:28][NH:29]2)=[CH:25][CH:24]=1

Participants

6

Reactant 3

HCID 31398ChlorosuccinimideHCID 66765235Ethyl 2-fluoro-3-mercaptobenzoateHCID 1181041884-(4-(6-chloro-2-cyclopropyl-3-((3-(ethoxycarbonyl)-2-fluorophenyl) thio)-7-fluoro-1H-indol-1-yl)-1H-pyrazol-1-yl)butanoic acid

Product 1

HCID 117979430ethyl 3-((6-chloro-7-fluoro-1H-indol-3-yl)thio)-2-fluorobenzoateYield 55.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of Intermediate A (1.18 g, 5.91 mmol) in CH2Cl2 (30 mL) under inert atmosphere was added NCS (792 mg, 5.91 mmol) at RT and stirred for 1 h. To this, indole 1 (Example 4, Step 1; 1.0 g, 5.91 mmol) in CH2Cl2 (20 mL) was added at RT and stirred for 4 h. After completion of the reaction by TLC, the reaction mixture was diluted with water (40 mL) and extracted with CH2Cl2 (2×60 mL). The combined organic extracts were washed with water (50 mL) and brine (50 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to obtain the crude. The crude was purified (silica gel; 10% EtOAc/Hexanes) to afford compound 2 (1.2 g, 55%) as a light brown solid. 1H NMR (500 MHz, DMSO-d6): δ 12.60 (br s, 1H), 8.00 (d, J=4.0 Hz, 1H), 7.61-7.57 (m, 1H), 7.24-7.17 (m, 2H), 7.09 (t, J=8.0 Hz, 1H), 6.90-6.86 (m, 1H), 4.34 (q, J=7.5 Hz, 2H), 1.32 (t, J=7.5 Hz, 3H); MS: m/z 368.6 (M+H+).

Workup

  1. stirringstirred for 4 h
  2. customAfter completion of the reaction by TLC
  3. extractionextracted with CH2Cl2 (2×60 mL)
  4. washThe combined organic extracts were washed with water (50 mL) and brine (50 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto obtain the crude
  9. customThe crude was purified (silica gel; 10% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-bc57e6c81fe746cb82144f34f21c6d47
Source dataset
uspto-grants-2016_05
Patent number
US09334261B2

Reaction notes

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