Cesium carbonate → [5-(3-Amino-3-methyl-but-1-ynyl)-2-methoxy-phenyl]-[6-(2,4-difluoro-phenylamino)-pyridin-3-yl]-methanone

HRID 896088Notes

Reaction equation

HRID 896088 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([O:25][CH3:26])=[C:6]([C:8]([C:10]2[CH:11]=[N:12][C:13]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=3[F:24])=[CH:14][CH:15]=2)=[O:9])[CH:7]=1.C([O-])([O-])=O.[Cs+].[Cs+].[CH3:33][C:34]([NH2:38])([CH3:37])[C:35]#[CH:36]>C(N(C(C)C)CC)(C)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[NH2:38][C:34]([CH3:37])([CH3:33])[C:35]#[C:36][C:2]1[CH:3]=[CH:4][C:5]([O:25][CH3:26])=[C:6]([C:8]([C:10]2[CH:11]=[N:12][C:13]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=3[F:24])=[CH:14][CH:15]=2)=[O:9])[CH:7]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 763193-Butyn-2-amine, 2-methyl-HCID 22349594(5-Bromo-2-methoxy-phenyl)-[6-(2,4-difluoro-phenylamino)-pyridin-3-yl]-methanone

Product 1

HCID 10180494[5-(3-Amino-3-methyl-but-1-ynyl)-2-methoxy-phenyl]-[6-(2,4-difluoro-phenylamino)-pyridin-3-yl]-methanone

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 81531DiisopropylethylamineSolvent

Procedure

(5-Bromo-2-methoxy-phenyl)-[6-(2,4-difluoro-phenylamino)-pyridin-3-yl]-methanone (1.36 g; 3.2 mmol) is dissolved in hot diisopropylethylamine (120 ml). PdCl2(PPh3)2 (680 mg; 0.97 mmol), Cs2CO3 (6.8 g; 0.02 mmol), CuI (0.68 g; 3.57 mmol) and 1,1-dimethyl-prop-2-ynylamine (6.8 ml; 65 mmol) are added and the mixture refluxed under argon for 30 min. The reaction mixture is decanted from the solid, evaporated, taken up in water and extracted three times with ethyl acetate. The combined organic phases are dried over Na2SO4 and evaporated to dryness. Purification via chromatography (SiO2; toluene/ethanol/NH3conc 96/4/0.2>94/6/0.3) yields the title compound as a slightly colored foam (1.14 g; 84%).

Workup

  1. temperaturethe mixture refluxed under argon for 30 min
  2. customThe reaction mixture is decanted from the solid
  3. customevaporated
  4. extractionextracted three times with ethyl acetate
  5. dry with materialThe combined organic phases are dried over Na2SO4
  6. customevaporated to dryness
  7. customPurification via chromatography (SiO2; toluene/ethanol/NH3conc 96/4/0.2>94/6/0.3)

Sources & evidence

ORD record
ord-aa4313d367454407a66153bd4db34413
Source dataset
uspto-grants-2005_07
Patent number
US06919336B2

Reaction notes

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