Potassium Carbonate → HCID 131733010, compound

HRID 706440Notes

Reaction equation

HRID 706440 reaction equation
I[C:2]1[CH:29]=[CH:28][C:5]2[N:6]([CH2:9][C:10]3[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]4[CH:19]=[N:20][C:21]([O:24][CH3:25])=[CH:22][CH:23]=4)=[C:12]([O:26][CH3:27])[CH:11]=3)[CH:7]=[N:8][C:4]=2[CH:3]=1.[NH:30]1[CH2:35][CH2:34][CH:33]([NH:36][C:37](=[O:43])[O:38][C:39]([CH3:42])([CH3:41])[CH3:40])[CH2:32][CH2:31]1.C(=O)([O-])[O-].[K+].[K+].N1CCC[C@H]1C(O)=O>CS(C)=O.[OH-].[NH4+].[Cu]I>[C:39]([O:38][C:37](=[O:43])[NH:36][CH:33]1[CH2:34][CH2:35][N:30]([C:2]2[CH:29]=[CH:28][C:5]3[N:6]([CH2:9][C:10]4[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]5[CH:19]=[N:20][C:21]([O:24][CH3:25])=[CH:22][CH:23]=5)=[C:12]([O:26][CH3:27])[CH:11]=4)[CH:7]=[N:8][C:4]=3[CH:3]=2)[CH2:31][CH2:32]1)([CH3:42])([CH3:40])[CH3:41]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 145742L-Proline2×HCID 7238334-(N-Boc-amino)piperidine2×HCID 1181141105-iodo-1-(3-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-1H-benzo[d]imidazole

Product 1

HCID 131733010HCID 131733010, compoundYield 60%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 679Dimethyl SulfoxideSolventHCID 14923Ammonium HydroxideSolvent

Conditions

Temperature
120 °C

Procedure

To a suspension of 5-iodo-1-(3-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-1H-benzo[d]imidazole (0.48 g, 0.96 mmol) in dimethyl sulfoxide (4 mL) was added tert-butyl piperidin-4-ylcarbamate (0.22 g, 1.05 mmol), copper(I) iodide (0.022 g, 0.11 mmol), potassium carbonate (0.32 g, 2.32 mmol), and L-proline (0.026 g, 0.23 mmol). The light yellow reaction mixture was heated to 120° C. After 16 h, additional portions tert-butyl piperidin-4-ylcarbamate (0.048 g, 0.47 mmol), copper(I) iodide (0.018 g, 0.095 mmol), and L-proline (0.022 g, 0.19 mmol) were added. Heating was continued for an additional 4 h. After a total of 20 h, the reaction mixture was allowed to cool to room temperature and was diluted with 3 N ammonium hydroxide solution (25 mL). The mixture was extracted with dichloromethane (×3). The combined organic phases were washed with water (×2), brine, dried over magnesium sulfate, filtered, and concentrated. Chromatographic purification (CombiFlash, 40 g SiO2 column, 1-10% methanol/dichloromethane elute) afforded 0.33 g (60%) of tert-butyl(1-(1-(3-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-1H-benzo[d]imidazol-5-yl)piperidin-4-yl)carbamate as an impure solid.

Workup

  1. temperatureHeating
  2. waitwas continued for an additional 4 h
  3. customAfter a total of 20 h
  4. temperatureto cool to room temperature
  5. extractionThe mixture was extracted with dichloromethane (×3)
  6. washThe combined organic phases were washed with water (×2), brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customChromatographic purification (CombiFlash, 40 g SiO2 column, 1-10% methanol/dichloromethane elute)

Sources & evidence

ORD record
ord-8efeba9129154bc795b7a72fdc17ccbc
Source dataset
uspto-grants-2015_11
Patent number
US09174986B2

Reaction notes

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