Methanesulfonic Acid → 4-(3-Chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(1-(2-hydroxyethoxyimino)-2-butyn-1-yl)quinazoline

HRID 220126Notes

Reaction equation

HRID 220126 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[C:25]([C:28](=O)[C:29]#[C:30][CH3:31])[CH:26]=3)[N:21]=[CH:20][N:19]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1.C([O:36][CH2:37][CH2:38][O:39][NH2:40])(=O)C.CS(O)(=O)=O.C(=O)(O)[O-].[Na+]>O1CCOCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[C:25]([C:28](=[N:40][O:39][CH2:38][CH2:37][OH:36])[C:29]#[C:30][CH3:31])[CH:26]=3)[N:21]=[CH:20][N:19]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1

Participants

6

Reactant 4

HCID 6395Methanesulfonic AcidHCID 516892Sodium BicarbonateHCID 467016214-(3-Chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(1-oxo-2-butyn-1-yl)quinazolineHCID 592596742-(Acetoxy)ethoxyamine

Product 1

HCID 866309264-(3-Chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(1-(2-hydroxyethoxyimino)-2-butyn-1-yl)quinazoline

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

4-(3-Chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(1-oxo-2-butyn-1-yl)quinazoline (VII-4, 10 g) was dissolved in 300 ml of 1,4-dioxane, 1.5 equivalent of 2-(acetoxy)ethoxyamine was added, and 28 ml of 2 mol/L aqueous methanesulfonic acid solution was added, followed by stirring at 60° C. for 17 hours. The reaction mixture was poured into aqueous saturated sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, and dried over sodium sulfate. The residue obtained by concentrating the filtrate was recrystallized from hydrous ethanol-water, filtered, and dried to obtain 4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(1-(2-hydroxyethoxyimino)-2-butyn-1-yl)quinazoline (VIII-33, 7.6 g) as a colorless solid.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with water
  3. dry with materialdried over sodium sulfate
  4. customThe residue obtained
  5. concentrationby concentrating the filtrate
  6. customwas recrystallized from hydrous ethanol-water
  7. filtrationfiltered
  8. customdried

Sources & evidence

ORD record
ord-7ac529203cb34241933a39f8a1f0b777
Source dataset
uspto-grants-2012_06
Patent number
US08202879B2

Reaction notes

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