Sodium Carbonate → 5-(1-phenyl-1H-1,3-benzodiazol-5-yl)-1-[3-(piperidin-1-yl)propyl]-1,2-dihydropyridin-2-one

HRID 991503Notes

Reaction equation

HRID 991503 reaction equation
I[C:2]1[CH:3]=[CH:4][C:5](=[O:17])[N:6]([CH2:8][CH2:9][CH2:10][N:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)[CH:7]=1.[C:18]1([N:24]2[C:28]3[CH:29]=[CH:30][C:31](B4OC(C)(C)C(C)(C)O4)=[CH:32][C:27]=3[N:26]=[CH:25]2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1.O>[C:18]1([N:24]2[C:28]3[CH:29]=[CH:30][C:31]([C:2]4[CH:3]=[CH:4][C:5](=[O:17])[N:6]([CH2:8][CH2:9][CH2:10][N:11]5[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]5)[CH:7]=4)=[CH:32][C:27]=3[N:26]=[CH:25]2)[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 120181725-iodo-1-(3-piperidin-1-yl-propyl)-1H-pyridin-2-oneHCID 120181731-Phenyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-benzoimidazole

Product 1

HCID 53294085-(1-phenyl-1H-1,3-benzodiazol-5-yl)-1-[3-(piperidin-1-yl)propyl]-1,2-dihydropyridin-2-oneYield 71%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
80 °C

Procedure

5-iodo-1-(3-piperidin-1-yl-propyl)-1H-pyridin-2-one (18) (0.096 g, 0.28 mmol), 1-phenyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-benzoimidazole (0.081 g, 0.25 mmol), palladium(II) acetate (0.003 g, 0.013 mmol), triphenylphosphine (0.010 g, 0.038 mmol) and sodium carbonate (0,080 g, 0.75 mmol) were stirred in 1.6 mL of a 3:1 mixture of dioxane/water. The mixture was degassed 3× by alternating vacuum and an argon atmosphere. The reaction was heated to 80° C. for 18 h, cooled and diluted with water. The aqueous phase was extracted 3× with EtOAc and the resulting organic phase was dried over Na2SO4, filtered and concentrated. Purification by flash column chromatography (eluted with 85:15 CH2Cl2/MeOH) afforded 0.073 g 5-(1-phenyl-1H-benzoimidazol-5-yl)-1-(3-piperidin-1-yl-propyl)-1H-pyridin-2-one (19) (71% yield). 1H NMR (CDCl3) δ9.60 (s, 1H), 7.90 (d, J=1.3 Hz, 1H), 7.74-7.67 (m, 2H), 7.64-7.48 (m, 6H), 7.39 (dd, J=2.5, 9.5 Hz, 1H), 6.68 (d, J=9.5 Hz, 1H), 4.13 (t, J=6.5 Hz, 2H), 2.42 (bs, 6H), 2.10 (t, J=6.5 Hz, 2H), 1.64 (m, 4H), 1.46 (m, 2H). Mass Spectrometry (for C26H28N4O): [M+H]+413.2334, theoretical 413.2336.

Workup

  1. customThe mixture was degassed 3×
  2. temperaturecooled
  3. additiondiluted with water
  4. extractionThe aqueous phase was extracted 3× with EtOAc
  5. dry with materialthe resulting organic phase was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification
  9. washby flash column chromatography (eluted with 85:15 CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-3860ab4bdb23438ba9128312cc106dd7
Source dataset
uspto-grants-2002_10
Patent number
US06465484B1

Reaction notes

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