Potassium Carbonate → 5-(5-Phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl)nicotinaldehyde

HRID 2036815Notes

Reaction equation

HRID 2036815 reaction equation
Cl[C:2]1[N:11]=[C:10]([NH:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:3]=1.CC1(C)C(C)(C)OB([C:34]2[CH:35]=[N:36][CH:37]=[C:38]([CH:41]=2)[CH:39]=[O:40])O1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O>[C:20]1([C:8]2[CH:7]=[CH:6][CH:5]=[C:4]3[C:9]=2[C:10]([NH:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)=[N:11][C:2]([C:34]2[CH:35]=[N:36][CH:37]=[C:38]([CH:41]=2)[CH:39]=[O:40])=[N:3]3)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 49926405-(Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-carbaldehydeHCID 866706132-chloro-5-phenyl-N-(pyridin-2-ylmethyl)quinazolin-4-amine

Product 1

HCID 866706175-(5-Phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl)nicotinaldehydeYield 100%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 2-chloro-5-phenyl-N-(pyridin-2-ylmethyl)quinazolin-4-amine (2 g, 5.7 mmol) in 1,4-dioxane (40 mL) and H2O (8 mL) under nitrogen was added 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinaldehyde (1.48 g, 6.30 mmol), and potassium carbonate (2.39 g, 17.0 mmol). Upon completion of addition, the reaction mixture was degassed with nitrogen for 15 min and then (1,1′-bis(diphenylphosphino)ferrocene)palladium (II) chloride dichloromethane complex (0.46 mg, 0.050 mmol) was added. The reaction mixture was again degassed for 10 min with nitrogen. At the conclusion of this period, the reaction mixture was stirred at 90° C. for 16 h, then allowed to cool to room temperature and quenched by the addition of water. The reaction mixture was transferred to a separation funnel and the aqueous layer was extracted with ethyl acetate. The combined organic portions were washed with water and saturated NaCl, dried over Na2SO4, filtered and concentrated under reduced pressure. The resulting concentrate was purified by silica gel column chromatography using 2.7% MeOH in DCM as eluent to afford 5-(5-phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl)nicotinaldehyde (1.8 g, 100% yield) as an off-white solid. LCMS Method Y: retention time 1.99 min; [M+1]=418.4.

Workup

  1. additionUpon completion of addition
  2. customthe reaction mixture was degassed with nitrogen for 15 min
  3. addition(1,1′-bis(diphenylphosphino)ferrocene)palladium (II) chloride dichloromethane complex (0.46 mg, 0.050 mmol) was added
  4. customThe reaction mixture was again degassed for 10 min with nitrogen
  5. temperatureto cool to room temperature
  6. customquenched by the addition of water
  7. customThe reaction mixture was transferred to a separation funnel
  8. extractionthe aqueous layer was extracted with ethyl acetate
  9. washThe combined organic portions were washed with water and saturated NaCl
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. concentrationThe resulting concentrate
  14. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-62b5b07ba43446f2877d1fa09287bb6a
Source dataset
uspto-grants-2013_11
Patent number
US08575184B2

Reaction notes

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