3-Pyridinylboronic acid → HCID 178487830, compound

HRID 1520318Notes

Reaction equation

HRID 1520318 reaction equation
Cl[C:2]1[N:11]=[C:10]([OH:12])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:13][CH3:14])[CH:8]=2)[N:3]=1.[N:15]1[CH:20]=[CH:19][CH:18]=[C:17](B(O)O)[CH:16]=1>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:14][O:13][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]=[C:2]([C:17]1[CH:16]=[N:15][CH:20]=[CH:19][CH:18]=1)[N:11]=[C:10]2[OH:12]

Participants

5

Reactant 2

HCID 27343783-Pyridinylboronic acidHCID 178487952HCID 178487952, compound

Product 1

HCID 178487830HCID 178487830, compoundYield 93.5%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

To a mixture of 2-chloro-6-methoxyquinazolin-4-ol (1.20 g, 5.7 mmol, 1.0 eq.), pyridin-3-ylboronic acid (1.27 g, 8.6 mmol, 1.5 eq.), K2 CO3 (2.37 g, 17.1 mmol, 3.0 eq.) in dioxane (100 mL) and 1H2O (10 ml) was added Pd(PPh3)2Cl2 (230 mg, 0.29 mmol, 0.05 eq.) under N2 atmosphere. The resulting mixture was stirred at 105° C. under N2 atmosphere overnight. After reaction was completed, the mixture was cooled to room temperature, and the resultant precipitate was removed by filtration. The filtrate was concentrated in vacuo and the residue was partitioned between H2O (30 mL) and ethyl acetate (100 mL×3). The combined organic layers were washed with brine, dried over MgSO4. After filtration and evaporation, the crude product was obtained, which was combined with the filter cake and dried in vacuo to give 1.35 g of 6-methoxy-2-(pyridin-3-yl) quinazolin-4-ol as a gray solid. LCMS m/z=254.1 (M+1) (Method B) (retention time=1.39 min). The crude product was used for the next step without further purification.

Workup

  1. customAfter reaction
  2. temperaturethe mixture was cooled to room temperature
  3. customthe resultant precipitate was removed by filtration
  4. concentrationThe filtrate was concentrated in vacuo
  5. customthe residue was partitioned between H2O (30 mL) and ethyl acetate (100 mL×3)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationAfter filtration and evaporation
  9. customthe crude product was obtained
  10. customdried in vacuo

Sources & evidence

ORD record
ord-d3c86268ef2344d298640cbdeaf24c49
Source dataset
uspto-grants-2015_07
Patent number
US09073890B2

Reaction notes

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