Tetrahydrofuran → 1-(3-benzofuranyl)methylcarbonyl-4-(1H-indol-4-yl)piperazine

HRID 1936615Notes

Reaction equation

HRID 1936615 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3]([CH2:10][C:11]([OH:13])=O)=[CH:2]1.[NH:14]1[C:22]2[C:17](=[C:18]([N:23]3[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]3)[CH:19]=[CH:20][CH:21]=2)[CH:16]=[CH:15]1.O1CCCC1>CN(C)C=O>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3]([CH2:10][C:11]([N:26]2[CH2:27][CH2:28][N:23]([C:18]3[CH:19]=[CH:20][CH:21]=[C:22]4[C:17]=3[CH:16]=[CH:15][NH:14]4)[CH2:24][CH2:25]2)=[O:13])=[CH:2]1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 5945904-(piperazin-1-yl)-1H-indoleHCID 27629402-(1-Benzofuran-3-yl)acetic acid

Product 1

HCID 224622841-(3-benzofuranyl)methylcarbonyl-4-(1H-indol-4-yl)piperazineYield 25.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-(3-benzofuranyl)acetic acid (0.95 g), 1-(1H-indol-4-yl)piperazine (1.3 g), and N,N-dicyclohexylcarbodiimide (1.3 g) in a mixture of dry tetrahydrofuran (50 mL) and dry dimethylformamide (10 mL) was stirred for 16 h at room temperature. Filtration and removal of solvent in vacuo gave an oil which was purified by flash chromatography (eluent: ethyl acetate/heptane/triethylamine 10:9:1) giving 1-(3-benzofuranyl)methylcarbonyl-4-(1H-indol-4-yl)piperazine (0.5 g) as an oil. The oil was dissolved in tetrahydrofuran (20 mL) and treated with a suspension of lithium aluminium hydride (0.26 g) in tetrahydrofuran (20 mL) at room temperature under a nitrogen atmosphere followed by reflux for 4 hours. The reaction mixture was cooled to 0° C. and treated subsequently with water (1 mL), 15% aq. sodium hydroxide (0.5 mL), and water (2.5 mL). After stirring for 30 min the mixture was filtered and concentrated. The remaining oil was dissolved in acetone followed by addition of oxalic acid and filtration, giving the title compound as a crystalline material (0.4 g). Mp 130-32° C. 1H NMR (DMSO-d6): 3.05-3.15 (m, 2H); 3.15-3.30 (m, 6H); 3.35 (s, 4H); 6.45 (s, 1H); 6.55 (d, 1H); 7.00 (t, 1H); 7.10 (d, 1H); 7.20-7.40 (m, 3H); 7.60 (d, 1H); 7.75 (d, 1H); 7.90 (s, 1H); 11.10 (s, 1H). MS m/z (%): 346 (MH+, 3%), 214 (31%), 199 (19%), 171 (14%).

Workup

  1. filtrationFiltration and removal of solvent in vacuo
  2. customgave an oil which
  3. customwas purified by flash chromatography (eluent: ethyl acetate/heptane/triethylamine 10:9:1)

Sources & evidence

ORD record
ord-01a2001f35604376b6c3b1ebd90b0877
Source dataset
uspto-grants-2002_05
Patent number
US06391882B1

Reaction notes

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