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

HRID 1473660Notes

Reaction equation

HRID 1473660 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:4]=1B(O)O.[Br:16][C:17]1[CH:26]=[C:25]2[C:20]([C:21](Cl)=[N:22][C:23]([CH3:27])=[N:24]2)=[CH:19][CH:18]=1.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:16][C:17]1[CH:26]=[C:25]2[C:20]([C:21]([C:4]3[CH:5]=[CH:6][C:7]([C:9]([F:12])([F:11])[F:10])=[CH:8][C:3]=3[O:2][CH3:1])=[N:22][C:23]([CH3:27])=[N:24]2)=[CH:19][CH:18]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 222478197-Bromo-4-chloro-2-methylquinazolineHCID 24901776(2-Methoxy-4-(trifluoromethyl)phenyl)boronic acid

Product 1

HCID 866877357-Bromo-4-(2-methoxy-4-(trifluoromethyl)phenyl)-2-methylquinazolineYield 51.7%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A solution of PdCl2(dppf)-CH2Cl2 adduct (0.159 g, 0.194 mmol), (2-methoxy-4-(trifluoromethyl)phenyl)boronic acid (0.940 g, 4.27 mmol), 7-bromo-4-chloro-2-methylquinazoline (ACES Pharma, 1.000 g, 3.88 mmol), and potassium carbonate (2.147 g, 15.53 mmol) in 12 mL dioxane was treated with 4 mL water and was allowed to stir overnight at room temperature. LC/MS showed mostly 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-4-(2-methoxy-4-(trifluoromethyl)phenyl)-2-methylquinazoline (0.797 g, 2.007 mmol, 51.7% yield). (M+H)+=396.9.

Workup

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

Sources & evidence

ORD record
ord-2cc2beaecb2a41c5b7644b8b2a313520
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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