Water → 4-(3-Chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(1-hydroxyethan-1-yl)quinazoline

HRID 220117Notes

Reaction equation

HRID 220117 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[N:27]=[CH:26]C3C(=CC=C(C=O)C=3)N=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[Mg]Br.O.C([O:37][CH2:38][CH3:39])(=O)C>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:5]3[C:4](=[CH:3][CH:2]=[C:7]([CH:38]([OH:37])[CH3:39])[CH:6]=3)[N:17]=[CH:26][N:27]=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 962WaterHCID 8857Ethyl AcetateHCID 86630922(3-Chloro-4-(3-fluorobenzyloxy)phenylamino)-6-formylquinazolineHCID 178418573HCID 178418573, compound

Product 1

HCID 577338134-(3-Chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(1-hydroxyethan-1-yl)quinazoline

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In 30 mL of tetrahydrofuran was dissolved 620 mg of 4 (3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-formylquinazoline (IV-1), the solution was cooled to 0° C. under the nitrogen atmosphere, and 4.9 mL of methylmagnesium bromide (0.93M tetrahydrofuran solution) was added dropwise. After the reaction at 0° C. for 1 hour under the nitrogen atmosphere, water and ethyl acetate were added to separate the layers. The organic layer was washed sequentially with water and aqueous saturated sodium chloride solution, and dried over magnesium sulfate. After concentration, the resulting crystal was washed with chloroform to obtain 330 mg of 4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(1-hydroxyethan-1-yl)quinazoline (VI-1).

Workup

  1. additionwas added dropwise
  2. additionwere added
  3. customto separate the layers
  4. washThe organic layer was washed sequentially with water and aqueous saturated sodium chloride solution
  5. dry with materialdried over magnesium sulfate
  6. concentrationAfter concentration
  7. washthe resulting crystal was washed with chloroform

Sources & evidence

ORD record
ord-5ac5cb67eea54af29eadb09ddba9026a
Source dataset
uspto-grants-2012_06
Patent number
US08202879B2

Reaction notes

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