Chlorosuccinimide → ethyl 3-((2,6-dichloro-7-fluoro-1-(1-propyl-1H-pyrazol-4-yl)-1H-indol-3-yl)thio)benzoate

HRID 522760Notes

Reaction equation

HRID 522760 reaction equation
[Cl:1][C:2]1[C:10]([F:11])=[C:9]2[C:5]([C:6]([S:20][C:21]3[CH:22]=[C:23]([CH:29]=[CH:30][CH:31]=3)[C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:7][N:8]2[C:12]2[CH:13]=[N:14][N:15]([CH2:17][CH2:18][CH3:19])[CH:16]=2)=[CH:4][CH:3]=1.C1C(=O)N([Cl:39])C(=O)C1>C(Cl)Cl.O>[Cl:39][C:7]1[N:8]([C:12]2[CH:13]=[N:14][N:15]([CH2:17][CH2:18][CH3:19])[CH:16]=2)[C:9]2[C:5]([C:6]=1[S:20][C:21]1[CH:22]=[C:23]([CH:29]=[CH:30][CH:31]=1)[C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:4][CH:3]=[C:2]([Cl:1])[C:10]=2[F:11]

Participants

5

Reactant 2

HCID 31398Chlorosuccinimide2×HCID 118094259ethyl 3-((6-chloro-7-fluoro-1-(1-propyl-1H-pyrazol-4-yl)-1H-indol-3-yl) thio)benzoate

Product 1

HCID 118094277ethyl 3-((2,6-dichloro-7-fluoro-1-(1-propyl-1H-pyrazol-4-yl)-1H-indol-3-yl)thio)benzoateYield 63.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of compound 4 (150 mg, 0.32 mmol) in CH2Cl2 (3 mL) under inert atmosphere was added NCS (87 mg, 0.65 mmol) at RT. After 16 h stirring, NCS (87 mg, 0.65 mmol) was added again at RT and stirred for additional 24 h. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was diluted with water (15 mL) and extracted with CH2Cl2 (2×20 mL). The combined organic extracts were washed with water (15 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to obtain the crude. This was purified by silica gel column chromatography using 7% EtOAc/n-Hexane to afford compound 5 (100 mg, 62%) as a brown solid. 1H NMR (500 MHz, CDCl3): δ 7.89 (s, 1H), 7.80-7.79 (m, 1H), 7.67 (s, 1H), 7.65 (s, 1H), 7.28-7.26 (m, 3H), 7.17-7.14 (m, 1H), 4.33 (q, J=7.5 Hz, 2H), 4.18 (t, J=7.5 Hz, 2H), 2.00-1.95 (m, 2H), 1.36 (t, J=7.5 Hz, 3H), 0.98 (t, J=7.5 Hz, 3H); LC-MS (ESI): 97.6%; m/z 492.4 (M+H+); (column: X Select CSH C-18, 50×3.0 mm, 3.5 μm); RT 5.07 min; 5 mM NH4OAc: ACN; 0.8 mL/min).

Workup

  1. stirringstirred for additional 24 h
  2. customafter completion of the reaction
  3. extractionextracted with CH2Cl2 (2×20 mL)
  4. washThe combined organic extracts were washed with water (15 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-87f7a23942c84dda8d9b510bd7ae66f0
Source dataset
uspto-grants-2016_05
Patent number
US09334261B2

Reaction notes

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