Cesium fluoride → Ethyl 2-(2-bromo-5-(1-(4-(1,3-dioxoisoindolin-2-yl)butyl)-2-phenyl-1H-indole-6-car-bonyl)thiophen-3-yl)acetate

HRID 1952509Notes

Reaction equation

HRID 1952509 reaction equation
[Br:1][C:2]1[S:3][C:4]([C:13]([C:15]2[CH:23]=[C:22]3[C:18]([CH:19]=[C:20]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[NH:21]3)=[CH:17][CH:16]=2)=[O:14])=[CH:5][C:6]=1[CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9].Br[CH2:31][CH2:32][CH2:33][CH2:34][N:35]1[C:39](=[O:40])[C:38]2=[CH:41][CH:42]=[CH:43][CH:44]=[C:37]2[C:36]1=[O:45].[F-].[Cs+]>CC#N>[Br:1][C:2]1[S:3][C:4]([C:13]([C:15]2[CH:23]=[C:22]3[C:18]([CH:19]=[C:20]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[N:21]3[CH2:31][CH2:32][CH2:33][CH2:34][N:35]3[C:39](=[O:40])[C:38]4[C:37](=[CH:44][CH:43]=[CH:42][CH:41]=4)[C:36]3=[O:45])=[CH:17][CH:16]=2)=[O:14])=[CH:5][C:6]=1[CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9]

Participants

5

Reactant 3

HCID 25953Cesium fluorideHCID 93575N-(4-Bromobutyl)phthalimideHCID 67495813HCID 67495813, compound

Product 1

HCID 67502223Ethyl 2-(2-bromo-5-(1-(4-(1,3-dioxoisoindolin-2-yl)butyl)-2-phenyl-1H-indole-6-car-bonyl)thiophen-3-yl)acetateYield 74%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of 4 (715 mg, 1.53 mmol), N-(4-bromobutyl)-phthalimide (888 mg, 3.15 mmol) in 20 mL CH3CN, CsF (1.24 g, 8.21 mmol) was added. The resulting mixture was refluxed for 5 hours and then concentrated in vacuo. MPLC purification (Hex:EtOAc/4:1) of the residue gave 5 as a yellow amorphous solid (666 mg, 74%). 1H NMR (400 MHz, CDCl3) δ 7.96 (s, 1H), 7.78-7.65 (m, 6H), 7.58 (s, 1H), 7.48-7.39 (m, 5H), 6.57 (s, 1H), 4.30 (t, J=7.2 Hz, 2H), 4.16 (q, J=7.2 Hz, 2H), 3.67 (s, 2H), 3.49 (t, J=6.8 Hz, 2H), 1.74-1.68 (m, 2H), 1.50-1.46 (m, 2H), and 1.26 (t, J=7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 187.33, 169.95, 168.50, 145.22, 144.25, 136.85, 135.71, 135.07, 134.18, 132.55, 132.15, 132.09, 130.69, 129.52, 128.96, 128.84, 128.74, 123.44, 121.48, 121.42, 120.53, 112.50, 103.12, 61.49, 43.67, 37.26, 35.37, 27.38, 25.81, and 14.44.

Workup

  1. temperatureThe resulting mixture was refluxed for 5 hours
  2. concentrationconcentrated in vacuo
  3. customMPLC purification (Hex:EtOAc/4:1) of the residue

Sources & evidence

ORD record
ord-b18b4d100beb4dfbba8980dd9a22ba2a
Source dataset
uspto-grants-2013_03
Patent number
US08404728B2

Reaction notes

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