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

HRID 1473673Notes

Reaction equation

HRID 1473673 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][C:29]([CH3:33])=[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][C:29]([CH3:33])=[N:30]2)=[CH:25][CH:24]=1

Participants

8

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 222478197-Bromo-4-chloro-2-methylquinazolineHCID 866877462-(4-(Difluoromethyl)-5-fluoro-2-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 866877517-Bromo-4-(4-(difluoromethyl)-5-fluoro-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)-5-fluoro-2-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (Intermediate SSSSS; 1.290 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)+=399.0.

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-9a2477d6a2e74816abf47d1baede9550
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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