Cesium carbonate → 4-(4-Benzenesulfonylphenylamino)-quinazoline-6-carboxylic acid methoxymethylamide

HRID 220124Notes

Reaction equation

HRID 220124 reaction equation
[CH3:1][O:2][CH2:3][NH:4][C:5]([C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[N:13]=[CH:12][N:11]=[C:10]2Cl)=[O:6].[C:18]1([S:24]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)(=[O:26])=[O:25])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[CH3:1][O:2][CH2:3][NH:4][C:5]([C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[N:13]=[CH:12][N:11]=[C:10]2[NH:33][C:30]1[CH:29]=[CH:28][C:27]([S:24]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)(=[O:26])=[O:25])=[CH:32][CH:31]=1)=[O:6]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 5166664-(Phenylsulfonyl)anilineHCID 866309234-Chloroquinazoline-6-carboxylic acid methoxymethylamide

Product 1

HCID 687536164-(4-Benzenesulfonylphenylamino)-quinazoline-6-carboxylic acid methoxymethylamideYield 66.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

4-Chloroquinazoline-6-carboxylic acid methoxymethylamide (XIV-1, 550 mg), 611 mg of 4-benzenesulfonylphenylamine, 49 mg of palladium (II) acetate, 190 mg of Xant phos and 997 mg of cesium carbonate were added to 1,4-dioxane (30 ml), and the interior of a reaction vessel was replaced with a nitrogen gas, followed by stirring at 100° C. for 2.5 hours. The reaction mixture was filtrated with Celite, and water was added to the filtrate, followed by extraction with ethyl acetate. The organic layer was washed with aqueous saturated sodium chloride solution, and dried over sodium sulfate. The filtrated was concentrated, and the residue was purified by silica gel column chromatography (eluting with ethyl acetate: methanol=95:5) to obtain 4-(4-benzenesulfonylphenylamino)-quinazoline-6-carboxylic acid methoxymethylamide (XI-3, 651 mg) as a pale yellow solid.

Workup

  1. customthe interior of a reaction vessel was replaced with a nitrogen gas
  2. filtrationThe reaction mixture was filtrated with Celite, and water
  3. additionwas added to the filtrate
  4. extractionfollowed by extraction with ethyl acetate
  5. washThe organic layer was washed with aqueous saturated sodium chloride solution
  6. dry with materialdried over sodium sulfate
  7. concentrationThe filtrated was concentrated
  8. customthe residue was purified by silica gel column chromatography (eluting with ethyl acetate: methanol=95:5)

Sources & evidence

ORD record
ord-5eab4296fb9c4af7b3fea190143cd9a9
Source dataset
uspto-grants-2012_06
Patent number
US08202879B2

Reaction notes

Loading…