Quinoxaline → Quinazoline

HRID 2037196Notes

Reaction equation

HRID 2037196 reaction equation
[CH2:1]=[C:2]1[CH2:7][CH2:6][CH2:5][CH2:4][NH:3]1.B1C2CCCC1CCC2.[N:17]1[C:26]2C(=CC=CC=2)N=C[CH:18]=1.C([O-])([O-])=O.[K+].[K+].B([O-])[O-].C([O-])(O)=O.[Na+]>CN(C=O)C.O>[N:3]1[C:2]2[C:1](=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH:26]=[N:17][CH:18]=1

Participants

8

Reactant 6

HCID 7045QuinoxalineHCID 11430Potassium CarbonateHCID 789669-Borabicyclo(3.3.1)nonaneHCID 516892Sodium BicarbonateHCID 178031432-MethylidenepiperidineHCID 178514824HCID 178514824, compound

Product 1

HCID 9210Quinazoline

Reagents, catalysts & solvents 1

HCID 21962138N,N-Dimethylformamide--water (1/1)Solvent

Conditions

Temperature
65 °C

Procedure

Methylene piperidine ED.8 (243 mg, 1.23 mmol) is combined with 9-BBN (2.46 mL, 0.5 M in THF) and heated to 65° C. for 1 h. Then the mixture is cooled to 20° C., quinoxaline D*.5 (300 mg, 1.23 mmol), Pd(dppf) (50 mg, 10 mol %) and K2CO3 (195 mg, 1.41 mmol) are placed in DMF/H2O (1.2 mL, 5:1) and slowly the freshly prepared boronate is added dropwise. The reaction mixture is heated to 60° C. for 2 h, cooled, combined with NaHCO3 and extracted with DCM (3×10 mL). The solvent is removed, the residue is purified by chromatography (45:55 to 90:10 in 6 min CH3CN/H2O) and quinoxaline D.51 (250 mg, 50%) is obtained.

Workup

  1. temperatureThen the mixture is cooled to 20° C.
  2. temperatureThe reaction mixture is heated to 60° C. for 2 h
  3. temperaturecooled
  4. extractionextracted with DCM (3×10 mL)
  5. customThe solvent is removed
  6. customthe residue is purified by chromatography (45:55 to 90:10 in 6 min CH3CN/H2O) and quinoxaline D.51 (250 mg, 50%)
  7. customis obtained

Sources & evidence

ORD record
ord-1965449d750b499da13f2a9318354e43
Source dataset
uspto-grants-2013_11
Patent number
US08575203B2

Reaction notes

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