1-(3-(Trifluoromethyl)benzyl)piperazine → 3,3-Bis(4-fluorophenyl)-1-(2-oxo-2-{4-[3-(trifluoromethyl)benzyl]piperazin-1-yl}ethyl)pyrrolidin-2-one

HRID 1667126Notes

Reaction equation

HRID 1667126 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[CH:4]=[C:5]([CH:13]=[CH:14][CH:15]=1)[CH2:6][N:7]1[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1.[F:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2([C:35]3[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=3)[CH2:29][CH2:28][N:27]([CH2:30][C:31](O)=[O:32])[C:26]2=[O:34])=[CH:21][CH:20]=1.Cl.C(N=C=NCCCN(C)C)C>ClCCl.CN(C)C1C=CN=CC=1>[F:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2([C:35]3[CH:36]=[CH:37][C:38]([F:41])=[CH:39][CH:40]=3)[CH2:29][CH2:28][N:27]([CH2:30][C:31](=[O:32])[N:10]3[CH2:11][CH2:12][N:7]([CH2:6][C:5]4[CH:13]=[CH:14][CH:15]=[C:3]([C:2]([F:1])([F:16])[F:17])[CH:4]=4)[CH2:8][CH2:9]3)[C:26]2=[O:34])=[CH:21][CH:20]=1

Participants

6

Reactant 3

HCID 20608551-(3-(Trifluoromethyl)benzyl)piperazineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 673571912-(3,3-Bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl)acetic acid

Product 1

HCID 574020393,3-Bis(4-fluorophenyl)-1-(2-oxo-2-{4-[3-(trifluoromethyl)benzyl]piperazin-1-yl}ethyl)pyrrolidin-2-one

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-(3-(trifluoromethyl)benzyl)piperazine (0.24 g, 1.00 mmol) in dichloromethane (25 mL) under nitrogen was added 2-(3,3-bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl)acetic acid (Example 58D, 0.33 g, 1.00 mmol) followed by N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (0.39 g, 2.00 mmol) and N,N-dimethylpyridin-4-amine (0.012 g, 0.10 mmol). The reaction mixture was stirred overnight at room temperature. The reaction was concentrated and the residue was partitioned in ethyl acetate/water (8:2). The organic layer was washed with water followed by brine, dried over magnesium sulfate, filtered, and concentrated. Silica gel chromatography eluting with 3% methanol/dichloromethane gave the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.41-7.59 (m, 4H), 7.27-7.35 (m, 4H), 6.96-7.03 (m, 4H), 4.18 (s, 2H), 3.59-3.63 (m, 2H), 3.53 (s, 2H), 3.51 (t, J=6.6 Hz, 2H), 3.41-3.45 (m, 2H), 2.77 (t, J=6.5 Hz, 2H), 2.40-2.44 (m, 2H), 2.31-2.35 (m, 2H); MS (DCI+) m/z 558 (M+H)+.

Workup

  1. concentrationThe reaction was concentrated
  2. customthe residue was partitioned in ethyl acetate/water (8:2)
  3. washThe organic layer was washed with water
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. washSilica gel chromatography eluting with 3% methanol/dichloromethane

Sources & evidence

ORD record
ord-357ce882e84e47bab3328c5900178623
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Reaction notes

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