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 1269152Notes

Reaction equation

HRID 1269152 reaction equation
C(=O)([O-])[O-].[K+].[K+].[I-].[Na+].[CH3:9][CH:10]([CH3:26])[C:11]([NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([CH:20]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)[CH:15]=1)=[O:12].Cl[CH2:28][CH2:29][C@H:30]([N:37]1[C:45](=[O:46])[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[C:38]1=[O:47])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>CN(C=O)C.O>[O:46]=[C:45]1[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[C:38](=[O:47])[N:37]1[C@H:30]([C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1)[CH2:29][CH2:28][N:23]1[CH2:24][CH2:25][CH:20]([C:16]2[CH:15]=[C:14]([NH:13][C:11](=[O:12])[CH:10]([CH3:26])[CH3:9])[CH:19]=[CH:18][CH:17]=2)[CH2:21][CH2:22]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 77%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of potassium carbonate (29.2 mg, 0.211 mmol), sodium iodide (47.5 mg, 0.317 mmol), 2-methyl-N-[3-(4-piperidinyl)phenyl]propanamide (51.8 mg, 0.211 mmol) and 2-[(1S)-3-chloro-1-phenylpropyl]-1H-isoindole-1,3(2H)-dione (63.1 mg, 0.211 mmol) in DMF (5.0 mL) was stirred at 100° C. for 3 hrs, at which time TLC indicated that the reaction was complete. The reaction mixture was cooled to room temperature, poured into water (50 mL) and the aqueous layer was extracted with methylene chloride (3×30 mL). The combined organic extracts were washed with brine (30 mL), dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by preparative TLC [2.5% NH3 (2.0 M in methanol) in CHCl3] to give the desired product (74.1 mg, 77%) as a thick oil: 1H NMR (400 MHz, CDCl3) δ 7.83 (apparent dd, 2H, J=2.9 Hz), 7.69 (apparent dd, 2H, J=2.9 Hz), 7.56 (apparent dt, 3H, J=2.9, 7.3 Hz), 7.33 (m, 4H), 7.21 (t, 1H, J=7.8 Hz), 7.09 (s, 1H), 6.81 (apparent d, 1H, J=7.8 Hz), 5.49 (apparent dd, 1H, J=5.5, 9.5 Hz), 2.98 (d, 1H, J=9.5 Hz), 2.87 (m, 2H), 2.50 (septet, 1H, J=6.7 Hz), 2.40–2.35 (m, 4H), 1.94 (m, 2H), 1.70–1.50 (m, 4H), 1.25 (d, 6H, J=7.9 Hz); ESMS m/e: 510.4 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionthe aqueous layer was extracted with methylene chloride (3×30 mL)
  3. washThe combined organic extracts were washed with brine (30 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by preparative TLC [2.5% NH3 (2.0 M in methanol) in CHCl3]

Sources & evidence

ORD record
ord-15d6f77183f44cb4afc07e26f0134aac
Source dataset
uspto-grants-2007_04
Patent number
US07199135B2

Reaction notes

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