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

HRID 1667172Notes

Reaction equation

HRID 1667172 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:38]3[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=3)[CH2:32][CH2:31][CH2:30][N:29]([CH2:33][C:34](O)=[O:35])[C:28]2=[O:37])=[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:34](=[O:35])[CH2:33][N:29]2[CH2:30][CH2:31][CH2:32][C:27]([C:24]3[CH:25]=[CH:26][C:21]([F:20])=[CH:22][CH:23]=3)([C:38]3[CH:39]=[CH:40][C:41]([F:44])=[CH:42][CH:43]=3)[C:28]2=[O:37])[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 673591112-(3,3-Bis(4-fluorophenyl)-2-oxopiperidin-1-yl)acetic acid

Product 1

HCID 452753911-[2-(4-Benzhydrylpiperazin-1-yl)-2-oxoethyl]-3,3-bis(4-fluorophenyl)piperidin-2-one

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-benzhydrylpiperazine (0.227 g, 0.90 mmol) in dichloromethane (15 mL) under nitrogen was added the product of Example 90D (0.31 g, 0.90 mmol) followed by N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (0.344 g, 1.80 mmol) and N,N-dimethylpyridin-4-amine (0.011 g, 0.09 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 7.38-7.42 (m, 4H), 7.15-7.32 (m, 10H), 6.93-7.00 (m, 4H), 4.23 (s, 1H), 4.16 (s, 2H), 3.62-3.66 (m, 2H), 3.47 (t, J=6.4 Hz, 2H), 3.40-3.45 (m, 2H), 2.55-2.65 (m, 2H), 2.36-2.43 (m, 4H), 1.77-1.86 (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-e0508fbf7fa34f3f89d1301cdc77b140
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Reaction notes

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