4-Fluoroaniline → (2S,4S)-4-fluoro-1-[[N-[4-[N-(4-fluorophenyl)amino]carbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]pyrrolidine-2-carbonitrile

HRID 227970Notes

Reaction equation

HRID 227970 reaction equation
[C:1]([C:4]12[CH2:11][CH2:10][C:7]([NH:12][CH2:13][C:14]([N:16]3[CH2:20][C@@H:19]([F:21])[CH2:18][C@H:17]3[C:22]#[N:23])=[O:15])([CH2:8][CH2:9]1)[CH2:6][CH2:5]2)(O)=[O:2].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[F:46][C:47]1[CH:53]=[CH:52][C:50]([NH2:51])=[CH:49][CH:48]=1>CN(C)C=O>[F:21][C@@H:19]1[CH2:20][N:16]([C:14](=[O:15])[CH2:13][NH:12][C:7]23[CH2:6][CH2:5][C:4]([C:1]([NH:51][C:50]4[CH:52]=[CH:53][C:47]([F:46])=[CH:48][CH:49]=4)=[O:2])([CH2:9][CH2:8]2)[CH2:11][CH2:10]3)[C@H:17]([C:22]#[N:23])[CH2:18]1

Participants

6

Reactant 4

HCID 97314-FluoroanilineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57634365(2S,4S)-1-[[N-(4-carboxybicyclo[2,2,2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile

Product 1

HCID 57756833(2S,4S)-4-fluoro-1-[[N-[4-[N-(4-fluorophenyl)amino]carbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]pyrrolidine-2-carbonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(2S,4S)-1-[[N-(4-Carboxybicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (30.0 mg), along with 1-hydroxybenzotriazole, was dissolved in N,N-dimethylformamide (1.0 mL). While the solution was chilled in an ice bath, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (53.4 mg) was added and the mixture was allowed to warm to room temperature and was stirred for 1 hour. Subsequently, 4-fluoroaniline (17.8 μL) was added and the mixture was stirred for additional 2 hours. The solvent was evaporated under reduced pressure and the resulting residue was purified by preparative thin-layer chromatography (solvent:dichloromethane:methanol=4:1) to give (2S,4S)-4-fluoro-1-[[N-[4-[N-(4-fluorophenyl)amino]carbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]pyrrolidine-2-carbonitrile (14.6 mg).

Workup

  1. temperatureWhile the solution was chilled in an ice bath
  2. stirringthe mixture was stirred for additional 2 hours
  3. customThe solvent was evaporated under reduced pressure
  4. customthe resulting residue was purified by preparative thin-layer chromatography (solvent:dichloromethane:methanol=4:1)

Sources & evidence

ORD record
ord-d39c1df564e540248bf5d51a3f093b82
Source dataset
uspto-grants-2009_07
Patent number
US07560569B2

Reaction notes

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