Potassium Carbonate → (4-(1-((R)-1-(2,4-dichlorophenyl)ethyl)-1H-benzo[d]imidazol-6-yl)-5,6-dihydropyridin-1(2H)-yl)((R)-piperidin-2-yl)methanone

HRID 1747161Notes

Reaction equation

HRID 1747161 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[CH:8][N:7]([C@@H:10]([C:12]3[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=3[Cl:19])[CH3:11])[C:6]=2[CH:20]=1.C(O[C:26]([N:28]1[CH2:33][CH:32]=[C:31](B(O)O)[CH2:30][CH2:29]1)=[O:27])(C)(C)C.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:19][C:13]1[CH:14]=[C:15]([Cl:18])[CH:16]=[CH:17][C:12]=1[C@H:10]([N:7]1[C:6]2[CH:20]=[C:2]([C:31]3[CH2:30][CH2:29][N:28]([C:26]([C@H:29]4[CH2:30][CH2:31][CH2:32][CH2:33][NH:28]4)=[O:27])[CH2:33][CH:32]=3)[CH:3]=[CH:4][C:5]=2[N:9]=[CH:8]1)[CH3:11]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 21931462(1-(tert-Butoxycarbonyl)-1,2,3,6-tetrahydropyridin-4-yl)boronic acidHCID 86688429(R)-6-bromo-1-(1-(2,4-dichlorophenyl)ethyl)-1H-benzo[d]imidazole

Product 1

HCID 71569868(4-(1-((R)-1-(2,4-dichlorophenyl)ethyl)-1H-benzo[d]imidazol-6-yl)-5,6-dihydropyridin-1(2H)-yl)((R)-piperidin-2-yl)methanone

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (R)-6-bromo-1-(1-(2,4-dichlorophenyl)ethyl)-1H-benzo[d]imidazole (1.3 g, 3.5 mmol), (N-t-butoxycarbonyl-1,2,3,6-tetrahydropyridin-4-yl)boronic acid pincol ester (1.2 g, 3.9 mmol), tetrakis(triphenylphosphine)palladium(0) (Pd(PPh3)4, 0.20 g, 0.18 mmol), and 2 M aqueous potassium carbonate (5.3 mL, 10.5 mmol) in toluene (10 mL) and ethanol (5 mL). The mixture was purged with nitrogen for 5 min, and then heated at 100° C. for 2 h. After cooling to room temperature, the mixture was extracted with ethyl acetate (20 mL). The organic layer was washed with brine, dried (Na2SO4), and concentrated in vacuo. The resulting crude material was purified by flash chromatography (SiO2, 0-100% ethyl acetate in hexanes) to afford the desired product in 90% purity (1.6 g, 3.4 mmol, 97%). MS: (ES) m/z calculated for C25H28Cl2N3O [M+H]+472.2, found 472.

Workup

  1. customThe mixture was purged with nitrogen for 5 min
  2. temperatureAfter cooling to room temperature
  3. extractionthe mixture was extracted with ethyl acetate (20 mL)
  4. washThe organic layer was washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe resulting crude material was purified by flash chromatography (SiO2, 0-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-012167bcad4a4c5eac6ee262c7b73581
Source dataset
uspto-grants-2015_10
Patent number
US09150550B2

Reaction notes

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