Cesium carbonate → Methyl 4'-(4-bromo-5-chloropyridin-2-ylamino)-5'-methoxy-2'-methylbiphenyl-4-carboxylate

HRID 1850930Notes

Reaction equation

HRID 1850930 reaction equation
[NH2:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([O:18][CH3:19])=[O:17])=[CH:12][CH:11]=2)=[C:4]([CH3:20])[CH:3]=1.Br[C:22]1[CH:27]=[C:26]([Br:28])[C:25]([Cl:29])=[CH:24][N:23]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1COCC1>[Br:28][C:26]1[C:25]([Cl:29])=[CH:24][N:23]=[C:22]([NH:1][C:2]2[C:7]([O:8][CH3:9])=[CH:6][C:5]([C:10]3[CH:15]=[CH:14][C:13]([C:16]([O:18][CH3:19])=[O:17])=[CH:12][CH:11]=3)=[C:4]([CH3:20])[CH:3]=2)[CH:27]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 534052462,4-Dibromo-5-chloropyridineHCID 59764521Methyl 4'-amino-5'-methoxy-2'-methylbiphenyl-4-carboxylate

Product 1

HCID 59764478Methyl 4'-(4-bromo-5-chloropyridin-2-ylamino)-5'-methoxy-2'-methylbiphenyl-4-carboxylate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
150 °C

Procedure

Methyl 4′-amino-5′-methoxy-2′-methylbiphenyl-4-carboxylate generated in Step 1 (200 mg, 0.75 mmol), 2,4-dibromo-5-chloropyridine (222 mg, 0.82 mmol, 1.1 equiv), Pd2(dba)3 (17 mg, 0.02 mmol, 0.025 equiv.), xantphos (22 mg, 0.04 mmol, 0.05 equiv.), and Cs2CO3 (365 mg, 1.1 mmol, 1.5 equiv.) are added to THF (5 mL). The resulting mixture is bubbled with N2 gas for 5 minutes and then heated at 150° C. for 4 hours. After cooling to room temperature, the reaction mixture is diluted into EtOAc and washed with H2O. The EtOAc layer is dried over Mg2SO4 and concentrated in vacuo. Silica gel chromatography (hexanes-EtOAc) affords Methyl 4′-(4-bromo-5-chloropyridin-2-ylamino)-5′-methoxy-2′-methylbiphenyl-4-carboxylate; MS m/z 461.0 (M+1).

Workup

  1. customThe resulting mixture is bubbled with N2 gas for 5 minutes
  2. temperatureAfter cooling to room temperature
  3. additionthe reaction mixture is diluted into EtOAc
  4. washwashed with H2O
  5. dry with materialThe EtOAc layer is dried over Mg2SO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e445b722358f466e8dfc0a6e00b2d90a
Source dataset
uspto-grants-2015_02
Patent number
US08957081B2

Reaction notes

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