Chlorosuccinimide → 6-chloro-2-cyclopropyl-1-(1-ethyl-1H-pyrazol-4-yl)-7-fluoro-1H-indole

HRID 522788Notes

Reaction equation

HRID 522788 reaction equation
[Cl:1][C:2]1[C:10]([F:11])=[C:9]2[C:5]([C:6](SC3C(F)=C(C=CC=3)C(OCC)=O)=[CH:7][N:8]2[C:12]2[CH:13]=[N:14][N:15]([CH2:17][CH3:18])[CH:16]=2)=[CH:4][CH:3]=1.[CH2:32]1[C:37](=O)N(Cl)C(=O)[CH2:33]1>C(Cl)Cl.O>[Cl:1][C:2]1[C:10]([F:11])=[C:9]2[C:5]([CH:6]=[C:7]([CH:33]3[CH2:32][CH2:37]3)[N:8]2[C:12]2[CH:13]=[N:14][N:15]([CH2:17][CH3:18])[CH:16]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 31398ChlorosuccinimideHCID 118094256ethyl 3-((6-chloro-1-(1-ethyl-1H-pyrazol-4-yl)-7-fluoro-1H-indol-3-yl)thio)-2-fluorobenzoate

Product 1

HCID 1181041966-chloro-2-cyclopropyl-1-(1-ethyl-1H-pyrazol-4-yl)-7-fluoro-1H-indoleYield 54.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of compound 3 (100 mg, 0.21 mmol) in CH2Cl2 (3 mL) under inert atmosphere was added NCS (58 mg, 0.43 mmol) at RT and stirred for 16 h. The reaction mixture was diluted with water (10 mL) and extracted with CH2Cl2 (2×15 mL). The combined organic extracts were dried over Na2SO4 and concentrated under reduced pressure to obtain the crude. The crude was purified (silica gel; 14-17% EtOAc/Hexanes) to afford 5 (35 mg, 33%) as an off-white solid. 1H NMR (400 MHz, CDCl3): δ 7.71-7.66 (m, 3H), 7.30 (d, J=7.6 Hz, 1H), 7.19 (dd, J=8.8, 6.4 Hz, 1H), 7.04-6.97 (m, 2H), 4.40 (q, J=7.2 Hz, 2H), 4.27 (q, J=7.6 Hz, 2H), 1.58 (t, J=7.6 Hz, 3H), 1.49 (t, J=7.2 Hz, 3H); LC-MS (ESI): m/z 496.7 (M+H+).

Workup

  1. extractionextracted with CH2Cl2 (2×15 mL)
  2. dry with materialThe combined organic extracts were dried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. customto obtain the crude
  5. customThe crude was purified (silica gel; 14-17% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-60fbfbe07df943788c654809e9430e75
Source dataset
uspto-grants-2016_05
Patent number
US09334261B2

Reaction notes

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