Water → 7-Bromo-4-(4-(difluoromethyl)-2-methoxyphenyl)-2-methylquinazoline

HRID 1473675Notes

Reaction equation

HRID 1473675 reaction equation
[F:1][CH:2]([F:20])[C:3]1[CH:8]=[CH:7][C:6](B2OC(C)(C)C(C)(C)O2)=[C:5]([O:18][CH3:19])[CH:4]=1.[Br:21][C:22]1[CH:31]=[C:30]2[C:25]([C:26](Cl)=[N:27][C:28]([CH3:32])=[N:29]2)=[CH:24][CH:23]=1.C(=O)([O-])[O-].[K+].[K+].O>O1CCOCC1.C(Cl)Cl.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:21][C:22]1[CH:31]=[C:30]2[C:25]([C:26]([C:6]3[CH:7]=[CH:8][C:3]([CH:2]([F:1])[F:20])=[CH:4][C:5]=3[O:18][CH3:19])=[N:27][C:28]([CH3:32])=[N:29]2)=[CH:24][CH:23]=1

Participants

8

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 222478197-Bromo-4-chloro-2-methylquinazolineHCID 866877552-(4-(Difluoromethyl)-2-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 866877547-Bromo-4-(4-(difluoromethyl)-2-methoxyphenyl)-2-methylquinazoline

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of PdCl2(dppf)-CH2Cl2 adduct (0.095 g, 0.116 mmol), 2-(4-(difluoromethyl)-2-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (Intermediate TTT) (0.863 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 at room temperature overnight. LC/MS showed mostly product, so the reaction mixture was diluted with DCM and filtered through a plug of Celite. The aqueous layer was removed and the organics concentrated. The crude residue was carried on to step 2 without purification. (M+H)+=381.0.

Workup

  1. filtrationfiltered through a plug of Celite
  2. customThe aqueous layer was removed
  3. customThe crude residue was carried on to step 2 without purification

Sources & evidence

ORD record
ord-4242b31093524fc3875d1888c17f367b
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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