Water → 7-Bromo-4-(4-(difluoromethyl)-5-fluoro-2-methoxyphenyl)quinazoline

HRID 1473669Notes

Reaction equation

HRID 1473669 reaction equation
[F:1][CH:2]([F:21])[C:3]1[C:8]([F:9])=[CH:7][C:6](B2OC(C)(C)C(C)(C)O2)=[C:5]([O:19][CH3:20])[CH:4]=1.[Br:22][C:23]1[CH:32]=[C:31]2[C:26]([C:27](Cl)=[N:28][CH:29]=[N:30]2)=[CH:25][CH:24]=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:22][C:23]1[CH:32]=[C:31]2[C:26]([C:27]([C:6]3[CH:7]=[C:8]([F:9])[C:3]([CH:2]([F:1])[F:21])=[CH:4][C:5]=3[O:19][CH3:20])=[N:28][CH:29]=[N:30]2)=[CH:25][CH:24]=1

Participants

8

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 167808557-Bromo-4-chloroquinazolineHCID 866877462-(4-(Difluoromethyl)-5-fluoro-2-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 866877457-Bromo-4-(4-(difluoromethyl)-5-fluoro-2-methoxyphenyl)quinazoline

Reagents, catalysts & solvents 3

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

Procedure

A solution of PdCl2(dppf)-CH2Cl2 adduct (0.101 g, 0.123 mmol), 2-(4-(difluoromethyl)-5-fluoro-2-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (Intermediate SSSSS; 1.365 g, 4.52 mmol), 7-bromo-4-chloroquinazoline (Synnovator, 1.000 g, 4.11 mmol), and potassium carbonate (2.270 g, 16.43 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)+=384.9.

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-f3935f0359ae483fa527b65f32c0cb9e
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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