Cesium carbonate → HCID 10162554, compound

HRID 896082Notes

Reaction equation

HRID 896082 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([O:25][CH3:26])=[C:6]([C:8]([C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=3[F:24])=[CH:12][CH:11]=2)=[O:9])[CH:7]=1.[CH3:27][N:28]1[CH2:33][CH2:32][N:31]([CH2:34][C:35]#[CH:36])[CH2:30][CH2:29]1.C([O-])([O-])=O.[Cs+].[Cs+].C(N(CC)C(C)C)(C)C>COCCOCCOC.CC(OC)(C)C.Cl.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>[F:24][C:18]1[CH:19]=[C:20]([F:23])[CH:21]=[CH:22][C:17]=1[NH:16][C:13]1[CH:14]=[CH:15][C:10]([C:8]([C:6]2[CH:7]=[C:2]([C:36]#[C:35][CH2:34][N:31]3[CH2:32][CH2:33][N:28]([CH3:27])[CH2:29][CH2:30]3)[CH:3]=[CH:4][C:5]=2[O:25][CH3:26])=[O:9])=[CH:11][CH:12]=1

Participants

10

Reactant 4

HCID 10796Cesium carbonateHCID 81531DiisopropylethylamineHCID 135140911-Methyl-4-(prop-2-yn-1-yl)piperazineHCID 22349575(5-Bromo-2-methoxy-phenyl)-[4-(2,4-difluoro-phenylamino)-phenyl]-methanone

Product 1

HCID 10162554HCID 10162554, compoundYield 32%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 313Hydrochloric AcidSolventHCID 8150DiglymeSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

(5-Bromo-2-methoxy-phenyl)-[4-(2,4-difluoro-phenylamino)-phenyl]-methanone (0.5 g; 1.18 mmol), 1-methyl-4-prop-2-ynyl-piperazine (0.33 g; 2.37 mmol), PdCl2(PPh3)2 (0.158 g; 0.22 mmol), Cs2CO3 (1.0 g; 3.1 mmol) and CuI (50 mg; 0.26 mmol) are dissolved in diethylene glycol dimethyl ether (10 ml) and N,N-diisopropylethylamine (5 ml) and heated to 140° C. for 1 hour. The reaction mixture is diluted with TBME, filtered, evaporated and purified by chromatography (SiO2, EtOAc/MeOH/NH3conc 100/0/0>90/10/1) to yield the crude title compound as brown foam. The latter is dissolved in 2N HCl, washed with EtOAc, Na2CO3 added to the aqueous phase and extracted with EtOAc. The organic phase is filtered through Alox and evaporated to give the pure product as yellow foam (177 mg; 32%).

Workup

  1. filtrationfiltered
  2. customevaporated
  3. custompurified by chromatography (SiO2, EtOAc/MeOH/NH3conc 100/0/0>90/10/1)
  4. customto yield the crude title compound as brown foam
  5. washwashed with EtOAc, Na2CO3
  6. additionadded to the aqueous phase
  7. extractionextracted with EtOAc
  8. filtrationThe organic phase is filtered through Alox
  9. customevaporated

Sources & evidence

ORD record
ord-c4d1e256d6fb4a36ba975b88c3925956
Source dataset
uspto-grants-2005_07
Patent number
US06919336B2

Reaction notes

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