Hydrochloric Acid → 2-(4-Benzoylpiperazin-1-yl)-4-amino-6,7-dimethoxyquinazoline

HRID 461337Notes

Reaction equation

HRID 461337 reaction equation
[C:1]1([Mg]Br)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17]2[N:26]=[C:25]([NH2:27])[C:24]3[C:19](=[CH:20][C:21]([O:30][CH3:31])=[C:22]([O:28][CH3:29])[CH:23]=3)[N:18]=2)[CH2:13][CH2:12]1)#N.Cl.[OH-:33].[Na+]>O1CCCC1>[C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17]2[N:26]=[C:25]([NH2:27])[C:24]3[C:19](=[CH:20][C:21]([O:30][CH3:31])=[C:22]([O:28][CH3:29])[CH:23]=3)[N:18]=2)[CH2:13][CH2:12]1)(=[O:33])[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 213933662-(4-Cyanopiperazin-1-yl)-4-amino-6,7-dimethoxyquinazolineHCID 178418255HCID 178418255, compound

Product 1

HCID 106919662-(4-Benzoylpiperazin-1-yl)-4-amino-6,7-dimethoxyquinazoline

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

Under anhydrous conditions, a solution of 5.43 g. (0.03 mole) of phenylmagnesium bromide in 100 ml. of tetrahydrofuran is swept with dry nitrogen and a solution of 3.15 g. (0.01 mole) of 2-(4-cyanopiperazin-1-yl)-4-amino 6,7-dimethoxyquinazoline in 75 ml. of the same solvent is added dropwise over 30 minutes at room temperature. When the addition is complete, the reaction mixture is heated at 65° C. for 6 hours, then allowed to stand at room temperature overnight. To the reaction mixture is then added 25 ml. of 2N hydrochloric acid and stirring is continued for an additional 30 minutes. The reaction mixture is then made alkaline with sodium hydroxide solution and the organic layer separated. The aqueous layer is extracted with 2 × 100 ml. of tetrahydrofuran and the combined organic layers are dried over anhydrous magnesium sulfate and evaporated to dryness to obtain the crude title compound which can be further purified by crystallization from ethanol or by column chromatography on silica gel.

Workup

  1. additionof the same solvent is added dropwise over 30 minutes at room temperature
  2. additionWhen the addition
  3. additionTo the reaction mixture is then added 25 ml
  4. waitis continued for an additional 30 minutes
  5. customthe organic layer separated
  6. extractionThe aqueous layer is extracted with 2 × 100 ml
  7. dry with materialof tetrahydrofuran and the combined organic layers are dried over anhydrous magnesium sulfate
  8. customevaporated to dryness

Sources & evidence

ORD record
ord-22adb447148448ddaef9953cfec34e4e
Source dataset
uspto-grants-1977_12
Patent number
US04062844

Reaction notes

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