Water → 7-Bromo-2-methoxy-4-(2-methoxy-4-(trifluoromethyl)phenyl)quinazoline

HRID 1473665Notes

Reaction equation

HRID 1473665 reaction equation
[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](Cl)=[N:7][C:8]([O:12][CH3:13])=[N:9]2)=[CH:4][CH:3]=1.[CH3:15][O:16][C:17]1[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[CH:19][C:18]=1B(O)O.C(=O)([O-])[O-].[K+].[K+].O>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([C:18]3[CH:19]=[CH:20][C:21]([C:23]([F:26])([F:25])[F:24])=[CH:22][C:17]=3[O:16][CH3:15])=[N:7][C:8]([O:12][CH3:13])=[N:9]2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 24901776(2-Methoxy-4-(trifluoromethyl)phenyl)boronic acidHCID 866877407-Bromo-4-chloro-2-methoxyquinazoline

Product 1

HCID 866877417-Bromo-2-methoxy-4-(2-methoxy-4-(trifluoromethyl)phenyl)quinazolineYield 5.39%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

The crude residue from step 2 was dissolved in 22 mL dioxane and was treated with PdCl2(dppf)-CH2Cl2 adduct (0.608 g, 0.745 mmol), (2-methoxy-4-(trifluoromethyl)phenyl)boronic acid (1.802 g, 8.19 mmol), potassium carbonate (4.12 g, 29.8 mmol), and 8 mL water was added. The reaction mixture was allowed to stir at room temperature overnight. LC/MS showed product, so the aqueous layer was removed, and the reaction mixture was concentrated. Purification of the crude residue by silica gel column chromatography (0-50% EtOAc/heptane) gave 7-bromo-2-methoxy-4-(2-methoxy-4-(trifluoromethyl)phenyl)quinazoline (0.166 g, 0.402 mmol, 5.39% yield). (M+H)+=413.0.

Workup

  1. additionwas added
  2. customso the aqueous layer was removed
  3. concentrationthe reaction mixture was concentrated
  4. customPurification of the crude residue by silica gel column chromatography (0-50% EtOAc/heptane)

Sources & evidence

ORD record
ord-0e4dd66f39f7463ea3ec55c906f37bc4
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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