Cesium carbonate → HCID 22142251, compound

HRID 2414485Notes

Reaction equation

HRID 2414485 reaction equation
[CH3:1][C:2]1[CH:11]=[CH:10][C:9](Cl)=[C:8]2[C:3]=1[C:4](=[O:18])[CH:5]=[C:6]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[O:7]2.[CH3:19][N:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2CCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCC1>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].O1CCCC1>[CH2:16]([O:15][C:13]([C:6]1[O:7][C:8]2[C:3]([C:4](=[O:18])[CH:5]=1)=[C:2]([CH3:1])[CH:11]=[CH:10][C:9]=2[N:23]1[CH2:24][CH2:25][N:20]([CH3:19])[CH2:21][CH2:22]1)=[O:14])[CH3:17]

Participants

8

Reactant 5

HCID 10796Cesium carbonateHCID 531671-MethylpiperazineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 22142227HCID 22142227, compoundHCID 22142249HCID 22142249, compound

Product 1

HCID 22142251HCID 22142251, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

Ethyl 5-methyl-8-chloro-4-oxo-4H-chromene-2-carboxylate (1.0 g, 3.6 mmol) as prepared in Reference Example 6c above, was azeotroped with anhydrous toluene then the white solid was dissolved in 100 ml anhydrous toluene in a 250 mL single-neck round bottom flask. The mixture was degassed by alternating argon sparge and vacuum (3×), and the following were added in order: N-methylpiperazine (0.6 ml, 5.37 mmol), (2′-dicyclohexylphosphanyl-biphenyl-2-yl)dimethyl-amine (JACS 1998, 120, p 9722) (40 mg, 0.1 mmol), tris(dibenzylideneacetone)dipalladium(0) (66 mg, 0.072 mmol) then cesium carbonate (1.6 g, 5.37 mmol). The mixture was again degassed via alternating argon sparge and vacuum and was heated at 80° C. for 17 h. Additional tris(dibenzylideneacetone)dipalladium(0) (66 mg, 0.072 mmol) and (2′-dicyclopentylphosphanyl-biphenyl-2-yl)-dimethyl-amine (40 g, 0.1 mmol) were added and the reaction was stirred at 80° C. for another four days at which time the conversion was still only about 50% complete by HPLC. Tetrahydrofuran (100 mL) was added, and the combined mixture was filtered, concentrated under vacuum and purified by chromatography on silica eluted with 2.5% methanol in chloroform. The desired fractions were concentrated under vacuum to yield a yellow powder (250 mg=21%).

Workup

  1. customwas azeotroped with anhydrous toluene
  2. dissolutionthe white solid was dissolved in 100 ml anhydrous toluene in a 250 mL single-neck round bottom flask
  3. customThe mixture was degassed
  4. customsparge
  5. additionvacuum (3×), and the following were added in order
  6. customThe mixture was again degassed
  7. customsparge
  8. filtrationthe combined mixture was filtered
  9. concentrationconcentrated under vacuum
  10. custompurified by chromatography on silica
  11. washeluted with 2.5% methanol in chloroform
  12. concentrationThe desired fractions were concentrated under vacuum
  13. customto yield a yellow powder (250 mg=21%)

Sources & evidence

ORD record
ord-12698dce6107477984c84486b6599930
Source dataset
uspto-grants-2004_11
Patent number
US06812225B2

Reaction notes

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