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

HRID 227975Notes

Reaction equation

HRID 227975 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]([F:56])([F:55])[C:48]1[CH:54]=[CH:53][C:51]([NH2:52])=[CH:50][CH:49]=1.CN(C1C=CC=CN=1)C>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[CH2:10][CH2:11][C:4]([C:1]([NH:52][C:51]4[CH:53]=[CH:54][C:48]([C:47]([F:46])([F:55])[F:56])=[CH:49][CH:50]=4)=[O:2])([CH2:9][CH2:8]2)[CH2:5][CH2:6]3)[C@H:17]([C:22]#[N:23])[CH2:18]1

Participants

7

Reactant 5

HCID 99644-(Trifluoromethyl)anilineHCID 218852-DimethylaminopyridineHCID 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 11259858(2S,4S)-4-fluoro-1-[[N-[4-[N-(4-trifluoromethylphenyl)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-trifluoromethylaniline (23.0 μL) was added and the mixture was stirred for additional 12 hours, followed by addition of dimethylaminopyridine (11.3 mg) and stirring for additional 24 hours. The solvent was then 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-trifluoromethylphenyl)amino]carbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]pyrrolidine-2-carbonitrile (10.1 mg).

Workup

  1. temperatureWhile the solution was chilled in an ice bath
  2. stirringthe mixture was stirred for additional 12 hours
  3. stirringstirring for additional 24 hours
  4. customThe solvent was then evaporated under reduced pressure
  5. customthe resulting residue was purified by preparative thin-layer chromatography (solvent:dichloromethane:methanol=4:1)

Sources & evidence

ORD record
ord-8cff378499cc4339bc5ba944d6335f98
Source dataset
uspto-grants-2009_07
Patent number
US07560569B2

Reaction notes

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