Cesium carbonate → N-(3,4-Dimethoxybenzyl)-3',5'-dimethyl-4-pyridin-3-ylbiphenyl-3-carboxamide

HRID 1948558Notes

Reaction equation

HRID 1948558 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:22]2[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=2)=[C:6]([CH:21]=1)[C:7]([NH:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([O:19][CH3:20])[CH:12]=1)=[O:8].[CH3:28][C:29]1[CH:30]=[C:31](B(O)O)[CH:32]=[C:33]([CH3:35])[CH:34]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[CH3:20][O:19][C:13]1[CH:12]=[C:11]([CH:16]=[CH:15][C:14]=1[O:17][CH3:18])[CH2:10][NH:9][C:7]([C:6]1[CH:21]=[C:2]([C:31]2[CH:32]=[C:33]([CH3:35])[CH:34]=[C:29]([CH3:28])[CH:30]=2)[CH:3]=[CH:4][C:5]=1[C:22]1[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=1)=[O:8]

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 27343493,5-Dimethylphenylboronic acidHCID 584084115-Bromo-N-(3,4-dimethoxybenzyl)-2-pyridin-3-ylbenzamide

Product 1

HCID 58408399N-(3,4-Dimethoxybenzyl)-3',5'-dimethyl-4-pyridin-3-ylbiphenyl-3-carboxamide

Reagents, catalysts & solvents 4

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

A solution of 1-3 (90 mg, 0.211 mmol, 1.0 equiv) in DMF (2 ml) in a microwave vial was treated with the 3,5-dimethylphenyl boronic acid (34.7 mg, 0.232 mmol, 1.1 equiv), cesium carbonate (0.632 mL of a 1M solution in water, 0.632 mmol, 3.0 equiv), and PdCl2(dppf)-CH2Cl2 adduct (17.20 mg, 0.021 mmol, 0.1 equiv). The mixture was heated to 150° C. in a microwave reactor for 10 minutes. The mixture was cooled to room temperature and diluted with EtOAc. The organic solution was washed with sat. aq. NH4Cl, dried over Na2SO4, filtered and concentrated. The crude material was purified by gradient elution on silica gel (0 to 100% EtOAc in hexanes) to yield impure material which was precipitated from ether/hexanes and filtered. The solid was isolated to afford the product (1-4) as a tan solid. HRMS [M+H] C26H27N5O3 calc'd 453.2173. found 453.2178.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. washThe organic solution was washed with sat. aq. NH4Cl
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified by gradient elution on silica gel (0 to 100% EtOAc in hexanes)
  7. customto yield impure material which
  8. customwas precipitated from ether/hexanes
  9. filtrationfiltered
  10. customThe solid was isolated

Sources & evidence

ORD record
ord-11298d43abc84d63bd1746caf6c524a7
Source dataset
uspto-grants-2013_03
Patent number
US08399494B2

Reaction notes

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