1,2-Dimethoxyethane → 7-Chloro-4-(4-fluoro-3,5-dimethylphenyl)quinazoline

HRID 1056445Notes

Reaction equation

HRID 1056445 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:12])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[F:13][C:14]1[C:19]([CH3:20])=[CH:18][C:17](B2OC(C)(C)C(C)(C)O2)=[CH:16][C:15]=1[CH3:30].C(=O)([O-])[O-].[Na+].[Na+].C(COC)OC>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[Cl:12][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([C:17]3[CH:18]=[C:19]([CH3:20])[C:14]([F:13])=[C:15]([CH3:30])[CH:16]=3)=[N:3][CH:4]=[N:5]2)=[CH:10][CH:9]=1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 2418814,7-DichloroquinazolineHCID 569731582-(4-Fluoro-3,5-dimethylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 1212668267-Chloro-4-(4-fluoro-3,5-dimethylphenyl)quinazolineYield 71.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

4,7-dichloroquinazoline (4.0 g, 20.1 mmol), 2-(4-fluoro-3,5-dimethylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (5.53 g, 22.1 mmol), sodium carbonate (5.33 g, 50.2 mmol), palladium tetrakis (0.70 g, 0.60 mmol), dimethoxyethane (“DME”) (160 mL), and water (40 mL) were combined in a three neck round bottom flask. A condenser was attached then the system was evacuated and purged with nitrogen three times. The reaction was heated to a vigorous reflux overnight. The reaction was diluted with ethyl acetate, water and brine. The aqueous was partitioned off and the organic was washed once with brine, dried with sodium sulfate, filtered then concentrated down to a yellow solid. The yellow solid was purified with silica gel using DCM to 85/15 DCM/ethyl acetate solvent system to get 4.1 g of light yellow solid for a 71% yield.

Workup

  1. customA condenser was attached
  2. customthe system was evacuated
  3. custompurged with nitrogen three times
  4. temperatureThe reaction was heated to
  5. temperaturea vigorous reflux overnight
  6. additionThe reaction was diluted with ethyl acetate, water and brine
  7. customThe aqueous was partitioned off
  8. washthe organic was washed once with brine
  9. dry with materialdried with sodium sulfate
  10. filtrationfiltered
  11. concentrationthen concentrated down to a yellow solid
  12. customThe yellow solid was purified with silica gel

Sources & evidence

ORD record
ord-f2e8d073b0254b32b08c2c4bfa8d35d5
Source dataset
uspto-grants-2016_07
Patent number
US09397302B2

Reaction notes

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