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

HRID 522790Notes

Reaction equation

HRID 522790 reaction equation
[F:1][C:2]1[C:12]([SH:13])=[CH:11][CH:10]=[CH:9][C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5].C1C(=O)N(Cl)C(=O)C1.[Cl:22][C:23]1[C:31]([F:32])=[C:30]2[C:26]([CH:27]=[CH:28][N:29]2[C:33]2[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=2)=[CH:25][CH:24]=1.C([O-])(O)=O.[Na+]>ClCCCl.O>[Cl:22][C:23]1[C:31]([F:32])=[C:30]2[C:26]([C:27]([S:13][C:12]3[C:2]([F:1])=[C:3]([CH:9]=[CH:10][CH:11]=3)[C:4]([O:6][CH2:7][CH3:8])=[O:5])=[CH:28][N:29]2[C:33]2[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=2)=[CH:25][CH:24]=1

Participants

7

Reactant 4

HCID 31398ChlorosuccinimideHCID 516892Sodium BicarbonateHCID 66765235Ethyl 2-fluoro-3-mercaptobenzoateHCID 1181041946-chloro-7-fluoro-1-(pyridin-3-yl)-1H-indole

Product 1

HCID 118104184ethyl 3-((6-chloro-7-fluoro-1-(pyridin-3-yl)-1H-indol-3-yl)thio)-2-fluorobenzoateYield 13.9%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 962WaterSolvent

Procedure

To a stirred solution of Intermediate A (243 mg, 1.21 mmol) in 1,2-dichloroethane (8 mL) under inert atmosphere was added NCS (163 mg, 1.21 mmol) at RT and stirred for 1 h. To this, compound 2 (200 mg, 0.81 mmol) in 1,2-dichloroethane (2 mL) and NaHCO3 (204 mg, 2.45 mmol) were added at RT. After 24 h stirring at RT, the reaction mixture was diluted with water (15 mL) and extracted with EtOAc (2×30 mL). The combined organic extracts were washed with water (30 mL) and brine (30 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 3 (50 mg, 9%) as an off-white solid. 1H NMR (500 MHz, DMSO-d6): δ 8.91 (s, 1H), 8.70 (d, J=5.0 Hz, 1H), 8.30 (s, 1H), 8.18-8.15 (m, 1H), 7.66-7.762 (m, 2H), 7.36-7.34 (m, 2H), 7.17-7.13 (m, 2H), 4.34 (q, J=7.5 Hz, 2H), 1.32 (t, J=7.5 Hz, 3H).

Workup

  1. stirringAfter 24 h stirring at RT
  2. extractionextracted with EtOAc (2×30 mL)
  3. washThe combined organic extracts were washed with water (30 mL) and brine (30 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto obtain the crude
  8. customThe crude was purified (silica gel; 10% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-d55b4336558148cf9ef1c52764de1399
Source dataset
uspto-grants-2016_05
Patent number
US09334261B2

Reaction notes

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