Piperazine → HCID 66784215, compound

HRID 1095430Notes

Reaction equation

HRID 1095430 reaction equation
Cl[CH2:2][CH2:3][CH2:4][C:5]([C:7]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([F:16])[CH:14]=2)[NH:9][CH:8]=1)=[O:6].[NH:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1>C(#N)C.[I-].[K+]>[F:16][C:13]1[CH:14]=[C:15]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[C:7]2[C:5](=[O:6])[CH2:4][CH2:3][CH2:2][N:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1

Participants

5

Reactant 2

HCID 4837PiperazineHCID 59799424HCID 59799424, compound

Product 1

HCID 66784215HCID 66784215, compoundYield 129.6%

Reagents, catalysts & solvents 2

HCID 4875Potassium IodideCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a magnetically stirred solution of 4-chloro-1-(5-fluoro-1H-indol-3-yl)-butan-1-one (10.93 g, 45.6 mmol) in acetonitrile (100 ml), piperazine (20.33 g ml, 236 mmol) and a small amount of potassium iodide (0.1 g) were added, and the resulting mixture was heated at 80° C. for 48 hours. The formed solid material was removed by filtration and the residue was concentrated in vacuo to give 37 g crude yield. This crude product was further purified by column chromatography (gradient: ethylacetate/methanol/25% aqueous ammonia=90/5/5 to methanol) to give 17.1 g crude 1-(5-fluoro-1H-indol-3-yl)-4-(piperazin-1-yl)-butan-1-one. Then this crude 1-(5-fluoro-1H-indol-3-yl)-4-(piperazin-1-yl)-butan-1 -one (10.71 g, 0.389 mol) was dissolved in dichloromethane (500 ml) and Boc2O (25.53 g, 0.117 mol) was added. The resulting mixture was stirred for 4 hours at room temperature. The mixture was successively washed with 5% aqueous NaHCO3 and water. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. Subsequent column chromatography (gradient: dichloro-methane/methanol=99/1 to dichloro-methane/methanol=90/10 (v/v)) gave pure 4-[4-(5-fluoro-1H-indol-3-yl)-4-oxobutyl]-piperazine-1-carboxylic acid tert-butyl ester (3.85 g, 37% yield). 1H-NMR (400 MHz, DMSO-d6) δ 1.38 (s, 9H), 1.80 (quintet, J=7, 2H), 2.25-2.35 (m, 6H), 2.84 (t, J=7, 2H), 3.22-3.32 (m, 4H), 7.06 (dt, J˜9 and 3, 1H), 7.47 (dd, J˜9 and 5, 1H), 7.85 (dd, J˜9 and 3, 1H), 8.38 (s, 1H), 12.01 (brs, 1H).

Workup

  1. customThe formed solid material was removed by filtration
  2. concentrationthe residue was concentrated in vacuo
  3. customto give 37 g crude
  4. customyield
  5. customThis crude product was further purified by column chromatography (gradient: ethylacetate/methanol/25% aqueous ammonia=90/5/5 to methanol)

Sources & evidence

ORD record
ord-b2c58b4ad5a247e795d589e19527a8b0
Source dataset
uspto-grants-2012_03
Patent number
US08138174B2

Reaction notes

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