Sodium Carbonate → N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-4-methyl-4'-(morpholinomethyl)-5-(N-(tetrahydro-2H-pyran-4-yl)acetamido)[1,1'-biphenyl]-3-carboxamide

HRID 1616439Notes

Reaction equation

HRID 1616439 reaction equation
Br[C:2]1[CH:3]=[C:4]([N:22]([CH:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[C:23](=[O:25])[CH3:24])[C:5]([CH3:21])=[C:6]([CH:20]=1)[C:7]([NH:9][CH2:10][C:11]1[C:12](=[O:19])[NH:13][C:14]([CH3:18])=[CH:15][C:16]=1[CH3:17])=[O:8].[O:32]1[CH2:37][CH2:36][N:35]([CH2:38][C:39]2[CH:44]=[CH:43][C:42](B(O)O)=[CH:41][CH:40]=2)[CH2:34][CH2:33]1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.CO.C(Cl)Cl>[CH3:17][C:16]1[CH:15]=[C:14]([CH3:18])[NH:13][C:12](=[O:19])[C:11]=1[CH2:10][NH:9][C:7]([C:6]1[CH:20]=[C:2]([C:42]2[CH:41]=[CH:40][C:39]([CH2:38][N:35]3[CH2:36][CH2:37][O:32][CH2:33][CH2:34]3)=[CH:44][CH:43]=2)[CH:3]=[C:4]([N:22]([CH:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[C:23](=[O:25])[CH3:24])[C:5]=1[CH3:21])=[O:8]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 10998582{4-[(Morpholin-4-yl)methyl]phenyl}boronic acidHCID 708723905-bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-3-(N-(tetrahydro-2H-pyran-4-yl)acetamido)benzamide

Product 1

HCID 70872604N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-4-methyl-4'-(morpholinomethyl)-5-(N-(tetrahydro-2H-pyran-4-yl)acetamido)[1,1'-biphenyl]-3-carboxamideYield 44.3%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 5-bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-3-(N-(tetrahydro-2H-pyran-4-yl)acetamido)benzamide (50 mg, 0.10 mmol), (4-(morpholinomethyl)phenyl)boronic acid (41 mg, 0.13 mmol), sodium carbonate (27 mg, 0.25 mmol) in 3 ml of dioxane was degassed with argon for 20 min, Pd(PPh3) (12 mg, 0.0012 mmol) was added to the mixture and heated to 100° C. for overnight. The reaction was cooled to room temperature and diluted with water, before extraction with 10% MeOH in DCM, the organic layers were dried over Na2SO4, concentrated and the resulting crude product purified by silica gel (100-200) chromatography to obtain the title compound (26 mg, 23%).

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. dry with materialthe organic layers were dried over Na2SO4
  3. concentrationconcentrated
  4. customthe resulting crude product purified by silica gel (100-200) chromatography

Sources & evidence

ORD record
ord-bbed09889722478cb0348cd9e089eb23
Source dataset
uspto-grants-2014_07
Patent number
US08765732B2

Reaction notes

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