Cesium carbonate → N,N-Dimethyl-2-(5-thiophen-2-yl-1H-indol-3-yl)-acetamide

HRID 2370424Notes

Reaction equation

HRID 2370424 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][C:12]([N:14]([CH3:16])[CH3:15])=[O:13].[S:17]1[CH:21]=[CH:20][CH:19]=[C:18]1B(O)O.C(=O)([O-])[O-].[Cs+].[Cs+].[OH-].[Na+]>COCCOC>[CH3:15][N:14]([CH3:16])[C:12](=[O:13])[CH2:11][C:5]1[C:4]2[C:8](=[CH:9][CH:10]=[C:2]([C:18]3[S:17][CH:21]=[CH:20][CH:19]=3)[CH:3]=2)[NH:7][CH:6]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonate2×HCID 14798Sodium HydroxideHCID 27339602-Thiopheneboronic acidHCID 104464242-(5-bromo-1H-indol-3-yl)-N,N-dimethyl-acetamide

Product 1

HCID 10356535N,N-Dimethyl-2-(5-thiophen-2-yl-1H-indol-3-yl)-acetamideYield 54%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of 2-(5-bromo-1H-indol-3-yl)-N,N-dimethyl-acetamide (Example 2) (227 mg, 0.81 mmol) in DME (5 mL) is degassed by sparging with argon for 10 minutes. Then thiophene-2-boronic acid (155 mg, 1.21 mmol), caesium carbonate (658 mg, 2.02 mmol), and π-allyl tri-isopropylphosphino palladium bromide (15.7 mg, 0.04 mmol) are added, and the mixture is heated under reflux. Two additional portions of caesium carbonate (103 mg, 0.81 mmol) are added after 20 hours and 24 hours to bring the reaction to completion. The black reaction mixture is poured into 2 N NaOH (10 mL), and extracted twice with ethyl acetate. After removal of the solvent, the residue is chromatographed on silica (CHCl3:MeOH 29:1 v:v) to give the title product (121 mg, 54%). 1H-NMR (CDCl3, 300 MHz) δ 2.96, 2.98 (2 s, 3H each, 2 CH3); 3.77 (s, 2H, CH2); 6.84 (d, 3J=2.2 Hz, H-2); 7.06 (dd, 3J=5.0 Hz, 3J=3.6 Hz, thiophene H-4); 7.21 (d, thiophene H-5); 7.21 (d, 3J=8.4 Hz, H-7); 7.25 (d, thiophene H-3); 7.40 (dd, 4J=1.8 Hz, H-6); 7.70 (d, H-4); 9.16 (br s, NH). 13C-NMR (CDCl3, 75 MHz) δ 31.02 (CH2); 36.00, 38.00 (2 CH3); 109.05 (C-3); 112.17 (C-7); 116.22 (C-4); 121.08 (C-6); 122.25 (thiophene C-3); 123.70 (thiophene C-5); 124.31 (C-2); 126.29 (thiophene C-2); 127.83 (C-9); 128.15 (thiophene C-4); 136.27 (C-8); 146.56 (C-5); 172.16 (CO).

Workup

  1. customby sparging with argon for 10 minutes
  2. temperaturethe mixture is heated
  3. temperatureunder reflux
  4. customthe reaction to completion
  5. customThe black reaction mixture
  6. extractionextracted twice with ethyl acetate
  7. customAfter removal of the solvent
  8. customthe residue is chromatographed on silica (CHCl3:MeOH 29:1 v:v)

Sources & evidence

ORD record
ord-7bc0707caf804c9b9a3a7329c1b0a927
Source dataset
uspto-grants-2014_04
Patent number
US08710093B2

Reaction notes

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