Cesium fluoride → Benzyl 4-(6-(5-bromo-4-(2-ethoxy-2-oxoethyl)thiophene-2-carbonyl)-1-(4-(1,3-dioxoisoindolin-2-yl)butyl)-1H-indol-2-yl)benzoate

HRID 1952531Notes

Reaction equation

HRID 1952531 reaction equation
[Br:1][C:2]1[S:6][C:5]([C:7]([C:9]2[CH:17]=[C:16]3[C:12]([CH:13]=[C:14]([C:18]4[CH:33]=[CH:32][C:21]([C:22]([O:24][CH2:25][C:26]5[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=5)=[O:23])=[CH:20][CH:19]=4)[NH:15]3)=[CH:11][CH:10]=2)=[O:8])=[CH:4][C:3]=1[CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36].Br[CH2:41][CH2:42][CH2:43][CH2:44][N:45]1[C:49](=[O:50])[C:48]2=[CH:51][CH:52]=[CH:53][CH:54]=[C:47]2[C:46]1=[O:55].[F-].[Cs+]>CC#N>[Br:1][C:2]1[S:6][C:5]([C:7]([C:9]2[CH:17]=[C:16]3[C:12]([CH:13]=[C:14]([C:18]4[CH:33]=[CH:32][C:21]([C:22]([O:24][CH2:25][C:26]5[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=5)=[O:23])=[CH:20][CH:19]=4)[N:15]3[CH2:41][CH2:42][CH2:43][CH2:44][N:45]3[C:49](=[O:50])[C:48]4[C:47](=[CH:54][CH:53]=[CH:52][CH:51]=4)[C:46]3=[O:55])=[CH:11][CH:10]=2)=[O:8])=[CH:4][C:3]=1[CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36]

Participants

5

Reactant 3

HCID 25953Cesium fluorideHCID 93575N-(4-Bromobutyl)phthalimideHCID 67496556Benzyl 4-(6-(5-bromo-4-(2-ethoxy-2-oxoethyl)thiophene-2-carbonyl)-1H-indol-2-yl)benzoate

Product 1

HCID 67495957Benzyl 4-(6-(5-bromo-4-(2-ethoxy-2-oxoethyl)thiophene-2-carbonyl)-1-(4-(1,3-dioxoisoindolin-2-yl)butyl)-1H-indol-2-yl)benzoateYield 69%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of 4 (76 mg, 0.13 mmol), N-(4-bromobutyl)-phthalimide (71 mg, 0.25 mmol) in 10 mL CH3CN, CsF (96 mg, 0.63 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 (60 mg, 69%). 1H NMR (400 MHZ, CDCl3) δ 8.13 (d, J=8.4 Hz, 2H), 7.96 (s, 1H), 7.74-7.35 (m, 14H), 6.62 (s, 1H), 5.39 (s, 2H), 4.30 (t, J=7.2 Hz, 2H), 4.16 (q, J=7.2 Hz, 2H), 3.66 (s, 2H), 3.49 (t, J=6.8 Hz, 2H), 1.70-1.66 (m, 2H), 1.48-1.45 (m, 2H), and 1.26 (t, J=7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 187.27, 169.94, 168.47, 166.11, 144.12, 143.76, 137.30, 137.13, 136.11, 135.81, 135.11, 134.22, 132.06, 131.88, 131.24, 130.37, 130.20, 129.31, 128.90, 128.61, 128.53, 123.43, 121.63, 120.86, 112.60, 104.17, 67.17, 61.49, 43.90, 37.22, 35.32, 27.38, 25.80, and 14.43.

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-5e121194095147d09ed0c95533d7b330
Source dataset
uspto-grants-2013_03
Patent number
US08404728B2

Reaction notes

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