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

HRID 1969343Notes

Reaction equation

HRID 1969343 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

Procedure

To a solution of 4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(1-oxo-2-butyn-1-yl)quinazoline (IV) (10 g) in 1,4-dioxane (300 mL) was added 2-(acetoxy)ethoxyamine (1.5 equiv) and then 2 mol/L methane sulfonic acid aq. solution (28 mL) and stirred for 17 hr at 60° C. The reaction mixture was poured into saturated sodium hydrogen carbonate aq. solution and extracted with ethyl acetate. Organic layer was washed with water and dried over sodium sulfate. The filtrate was concentrated and the residue was recrystallized from hydrous ethanol-water, filtered and dried to give 4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(1-(2-hydroxyethoxyimino)-2-butyn-1-yl)quinazoline (VIII) (7.6 g) as a colorless solid.

Workup

  1. extractionextracted with ethyl acetate
  2. washOrganic layer was washed with water
  3. dry with materialdried over sodium sulfate
  4. concentrationThe filtrate was concentrated
  5. customthe residue was recrystallized from hydrous ethanol-water
  6. filtrationfiltered
  7. customdried

Sources & evidence

ORD record
ord-53cd6f1fa2684dc5a20dd752a42a2d7d
Source dataset
uspto-grants-2013_04
Patent number
US08426589B2

Reaction notes

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