Potassium Phosphate, Tribasic → 4-[3-(6-Amino-pyridin-3-ylethynyl)-2-ethyl-pyridin-4-yl]-2-chloro-benzoic acid methyl ester

HRID 1529218Notes

Reaction equation

HRID 1529218 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH2:8][CH3:9])[C:3]=1[C:10]#[C:11][C:12]1[CH:13]=[CH:14][C:15]([NH2:18])=[N:16][CH:17]=1.[Cl:19][C:20]1[CH:21]=[C:22](B(O)O)[CH:23]=[CH:24][C:25]=1[C:26]([O:28][CH3:29])=[O:27].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>COCCOC.O.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]>[CH3:29][O:28][C:26](=[O:27])[C:25]1[CH:24]=[CH:23][C:22]([C:2]2[CH:7]=[CH:6][N:5]=[C:4]([CH2:8][CH3:9])[C:3]=2[C:10]#[C:11][C:12]2[CH:17]=[N:16][C:15]([NH2:18])=[CH:14][CH:13]=2)=[CH:21][C:20]=1[Cl:19]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 230053353-Chloro-4-(methoxycarbonyl)benzeneboronic acidHCID 582353135-(4-Chloro-2-ethyl-pyridin-3-ylethynyl)-pyridin-2-ylamine

Product 1

HCID 582353234-[3-(6-Amino-pyridin-3-ylethynyl)-2-ethyl-pyridin-4-yl]-2-chloro-benzoic acid methyl ester

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

The title compound is synthesized according to general procedure GP3 starting from 2.0 g (7.8 mmol) 5-(4-Chloro-2-ethyl-pyridin-3-ylethynyl)-pyridin-2-ylamine (A-30) using 2.5 g (11.6 mmol) 3-chloro-4-methoxycarbonylphenyl boronic acid, 335 mg (0.39 mmol) Pd2(dba)3, 555 mg (1.2 mmol) X-Phos and 2.7 g (11.6 mmol) K3PO4 in a mixture of 100 mL DME and 20 mL water. The reaction mixture is stiffed under reflux for 4 days. The DME is removed under reduced pressure and the aqueous is extracted with ethyl acetate. The organic phase is dried over Na2SO4, filtered and the solvent removed under vacuum. The product is purified by chromatography on silica gel using an DCM/MeOH-gradient. Yield: 0.59 g (19%).

Workup

  1. temperatureunder reflux for 4 days
  2. customThe DME is removed under reduced pressure
  3. extractionthe aqueous is extracted with ethyl acetate
  4. dry with materialThe organic phase is dried over Na2SO4
  5. filtrationfiltered
  6. customthe solvent removed under vacuum
  7. customThe product is purified by chromatography on silica gel using an DCM/MeOH-gradient

Sources & evidence

ORD record
ord-0876d95a32a5447b8d447ca84a74121c
Source dataset
uspto-grants-2015_07
Patent number
US09090564B2

Reaction notes

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