Benzhydrylpiperazine → 1-[2-(4-Benzhydrylpiperazin-1-yl)-2-oxoethyl]-3,3-bis(4-fluorophenyl)pyrrolidin-2-one

HRID 1667124Notes

Reaction equation

HRID 1667124 reaction equation
[CH:1]([N:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2([C:37]3[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=3)[CH2:31][CH2:30][N:29]([CH2:32][C:33](O)=[O:34])[C:28]2=[O:36])=[CH:23][CH:22]=1.Cl.C(N=C=NCCCN(C)C)C>ClCCl.CN(C)C1C=CN=CC=1>[CH:1]([N:14]1[CH2:19][CH2:18][N:17]([C:33](=[O:34])[CH2:32][N:29]2[CH2:30][CH2:31][C:27]([C:24]3[CH:25]=[CH:26][C:21]([F:20])=[CH:22][CH:23]=3)([C:37]3[CH:38]=[CH:39][C:40]([F:43])=[CH:41][CH:42]=3)[C:28]2=[O:36])[CH2:16][CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 70048BenzhydrylpiperazineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 673571912-(3,3-Bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl)acetic acid

Product 1

HCID 451098791-[2-(4-Benzhydrylpiperazin-1-yl)-2-oxoethyl]-3,3-bis(4-fluorophenyl)pyrrolidin-2-one

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-benzhydrylpiperazine (0.54 g, 2.14 mmol) in dichloromethane (20 mL) under nitrogen was added the product from Example 58D (0.71 g, 2.14 mmol) followed by N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (0.82 g, 4.29 mmol) and N,N-dimethylpyridin-4-amine (0.013 g, 0.11 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, 400 mL). The organic layer was washed with water followed by brine, dried over magnesium sulfate, filtered, and concentrated. Silica gel chromatography eluting with ethyl acetate/hexane (1:3) gave the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.37-7.41 (m, 4H), 7.25-7.33 (m, 8H), 7.16-7.23 (m, 2H), 6.94-7.01 (m, 4H), 4.19 (s, 1H), 4.14 (s, 2H), 3.58 (t, J=4.7 Hz, 2H), 3.49 (t, J=6.5 Hz, 2H), 3.38-3.42 (m, 2H), 2.75 (t, J=6.5 Hz, 2H), 2.36 (t, J=4.8 Hz, 2H), 2.29 (t, J=4.6 Hz, 2H).

Workup

  1. concentrationThe reaction was concentrated
  2. customthe residue was partitioned in ethyl acetate/water (8:2, 400 mL)
  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 ethyl acetate/hexane (1:3)

Sources & evidence

ORD record
ord-73ad7792ef2645619b7afdb2b1629d1e
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Reaction notes

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