Sodium Iodide → N-(3-{1-[(3S)-3-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-YL)-3-phenylpropyl]-4-piperidinyl}phenyl)-2-methylpropanamide

HRID 1832210Notes

Reaction equation

HRID 1832210 reaction equation
Cl[CH2:2][CH2:3][C@H:4]([N:11]1[C:19](=[O:20])[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12]1=[O:21])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[CH3:22][CH:23]([CH3:39])[C:24]([NH:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([CH:33]2[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]2)[CH:28]=1)=[O:25].C([O-])([O-])=O.[K+].[K+].[Na+].[I-]>CN(C=O)C.O>[O:21]=[C:12]1[C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:19](=[O:20])[N:11]1[C@H:4]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[CH2:3][CH2:2][N:36]1[CH2:37][CH2:38][CH:33]([C:29]2[CH:28]=[C:27]([NH:26][C:24](=[O:25])[CH:23]([CH3:22])[CH3:39])[CH:32]=[CH:31][CH:30]=2)[CH2:34][CH2:35]1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 167572552-methyl-N-[3-(4-piperidyl)phenyl]propanamideHCID 207229752-[(1S)-3-Chloro-1-Phenylpropyl]-1H-Isoindole-1,3(2H)-Dione

Product 1

HCID 60078705N-(3-{1-[(3S)-3-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-YL)-3-phenylpropyl]-4-piperidinyl}phenyl)-2-methylpropanamideYield 74%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 2-[(1S)-3-chloro-1-phenylpropyl]-1H-isoindole-1,3(2H)-dione (4.50 g, 15.0 mmol), 2-methyl-N-[3-(4-piperidinyl)phenyl]propanamide (4.26 g, 15.0 mmol), K2CO3 (4.16 g, 30.0 mmol), and NaI (3.40 g, 20.0 mmol) in DMF (40 mL) was stirred at 90° C. for 12 hrs. The reaction mixture was diluted with water (50 mL), extracted with CH2Cl2 (3×50 mL), and the combined organic extracts were washed with brine (50 mL), dried over MgSO4, and concentrated under reduced pressure. The residue was purified by chromatography on silica using 5% of NH3 (2.0 M in methanol) in CH2Cl2 to give the desired product (5.10 g, 74%). 1H NMR (400 MHz, CDCl3) δ 7.83 (d, 1H, J=5.5 Hz), 7.82 (d, 1H, J=5.5 Hz), 7.71 (d, 1H, J=5.5 Hz), 7.70 (d, 1H, J=5.4 Hz), 7.56 (d, 2H, J=7.1 Hz), 7.35–7.27 (m, 5H), 7.22 (t, 1H, J=7.5 Hz), 7.09 (s, 1H), 6.81 (d, 1H, J=7.8 Hz), 5.49 (dd, 1H, J=5.5, 9.6 Hz), 2.97 (d, 1H, J=10.1 Hz), 2.92–2.82 (m, 2H), 2.44 (sept, 1H, J=6.7 Hz), 2.40–2.29 (m, 3H), 2.00–1.83 (m, 2H), 1.79–1.39 (m, 5H), 1.26 (d, 6H, J=6.9 Hz); ESMS m/e: 510.4 (M+H)+.

Workup

  1. extractionextracted with CH2Cl2 (3×50 mL)
  2. washthe combined organic extracts were washed with brine (50 mL)
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by chromatography on silica using 5% of NH3 (2.0 M in methanol) in CH2Cl2

Sources & evidence

ORD record
ord-22ba5a7a8565417eb8ff8c04aeda92b0
Source dataset
uspto-grants-2006_06
Patent number
US07067534B1

Reaction notes

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