1-(Bis(4-fluorophenyl)methyl)piperazine → 1-(2-{4-[Bis(4-fluorophenyl)methyl]piperazin-1-yl}-2-oxoethyl)-3,3-diphenylpiperidin-2-one

HRID 1667159Notes

Reaction equation

HRID 1667159 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)[N:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[CH:4][CH:3]=1.[O:22]=[C:23]1[C:28]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:27][CH2:26][CH2:25][N:24]1[CH2:41][C:42](O)=[O:43].Cl.C(N=C=NCCCN(C)C)C>ClCCl.CN(C)C1C=CN=CC=1>[F:21][C:18]1[CH:19]=[CH:20][C:15]([CH:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[N:9]2[CH2:10][CH2:11][N:12]([C:42](=[O:43])[CH2:41][N:24]3[CH2:25][CH2:26][CH2:27][C:28]([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[C:23]3=[O:22])[CH2:13][CH2:14]2)=[CH:16][CH:17]=1

Participants

6

Reactant 3

HCID 1529321-(Bis(4-fluorophenyl)methyl)piperazineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 673592802-(2-Oxo-3,3-diphenylpiperidin-1-yl)acetic acid

Product 1

HCID 573933231-(2-{4-[Bis(4-fluorophenyl)methyl]piperazin-1-yl}-2-oxoethyl)-3,3-diphenylpiperidin-2-one

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-(bis(4-fluorophenyl)methyl)piperazine (0.14 g, 0.5 mmol) in dichloromethane (10 mL) under nitrogen was added 2-(2-oxo-3,3-diphenylpiperidin-1-yl)acetic acid (Example 68E, 0.16 g, 0.50 mmol) followed by N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (0.19 g, 1.00 mmol) and N,N-dimethylpyridin-4-amine (6 mg, 0.05 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 7.18-7.36 (m, 14H), 6.95-7.01 (m, 4H), 4.22 (s, 1H), 4.19 (s, 2H), 3.63 (t, J=4.7 Hz, 2H), 3.48 (t, J=6.4 Hz, 2H), 3.41-3.46 (m, 2H), 2.60-2.65 (m, 2H), 2.31-2.39 (m, 4H), 1.78-1.87 (m, 2H)); MS (DCI+) m/z 580 (M+H)+.

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-5c8c38f060824c5fb7a60316f6f4aa18
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Reaction notes

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