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

HRID 1275552Notes

Reaction equation

HRID 1275552 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 3x 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 3x 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 (CDC13) o 9.60 (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. ##STR28##

Workup

  1. customThe mixture was degassed 3x
  2. temperaturecooled
  3. additiondiluted with water
  4. extractionThe aqueous phase was extracted 3x 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-0d56e135287f4436afccf9856debe137
Source dataset
uspto-grants-2000_12
Patent number
US06162804

Reaction notes

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