Potassium Phosphate, Tribasic → HCID 86703937, compound

HRID 1049940Notes

Reaction equation

HRID 1049940 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[C:7]([C:13]([O:15]C)=[O:14])[CH:8]=[C:9](Cl)[CH:10]=2)[N:5]=[CH:4][N:3]=1.[F:17][C:18]1[CH:19]=[C:20](B(O)O)[CH:21]=[CH:22][CH:23]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl.O1CCOCC1>[NH2:1][C:2]1[C:11]2[C:6](=[C:7]([C:13]([OH:15])=[O:14])[CH:8]=[C:9]([C:22]3[CH:21]=[CH:20][CH:19]=[C:18]([F:17])[CH:23]=3)[CH:10]=2)[N:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27339863-Fluorophenylboronic acidHCID 86703938HCID 86703938, compound

Product 1

HCID 86703937HCID 86703937, compoundYield 68.6%

Reagents, catalysts & solvents 2

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a 20 mL screw-cap vial was added methyl 4-amino-6-chloro-quinazoline-8-carboxylate (640 mg; 1.8 mmol), (3-fluorophenyl)boronic acid (2 equiv., 3.6 mmol, 0.49753 g), dioxane (10 mL), Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (0.05 equiv. 0.09 mmol, 0.062945 g), and potassium phosphate tribasic (2M in water, 4 equiv., 7.2 mmol, 3.6 mL). The reaction was capped and shaken at 100° C. for 4 h. LCMS showed complete Suzuki coupling, as well as saponified ester. The Reaction was cooled to room temperature, and partitioned with water and ethyl acetate. The organic was extracted 2 additional times with water. The combined aqueous was acidified to pH 2 with conc. HCl. The resulting precipitate was collected via filtration, yielding 350 mg of 4-amino-6-(3-fluorophenyl)quinazoline-8-carboxylic acid, ˜85% pure. Product was carried directly on to the amide formation. LCMS M/Z (M+H)=284.

Workup

  1. customTo a 20 mL screw-cap vial
  2. customThe reaction was capped
  3. temperatureThe Reaction was cooled to room temperature
  4. custompartitioned with water and ethyl acetate
  5. extractionThe organic was extracted 2 additional times with water
  6. filtrationThe resulting precipitate was collected via filtration

Sources & evidence

ORD record
ord-1ad7d12c460c4a25b8110358aa8bd9bf
Source dataset
uspto-grants-2016_07
Patent number
US09382241B2

Reaction notes

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