Piperazine → 3-Fluoro-2-(7-methyl-4-(piperazin-1-yl)quinazolin-2-yl)phenol

HRID 2062174Notes

Reaction equation

HRID 2062174 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH3:12])=[CH:9][CH:10]=2)[N:5]=[C:4]([C:13]2[C:18]([F:19])=[CH:17][CH:16]=[CH:15][C:14]=2[OH:20])[N:3]=1.[NH:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1.C(N(CC)CC)C>C(Cl)Cl>[F:19][C:18]1[C:13]([C:4]2[N:3]=[C:2]([N:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[C:11]3[C:6](=[CH:7][C:8]([CH3:12])=[CH:9][CH:10]=3)[N:5]=2)=[C:14]([OH:20])[CH:15]=[CH:16][CH:17]=1

Participants

5

Reactant 3

HCID 4837PiperazineHCID 8471TriethylamineHCID 1361213752-(4-Chloro-7-methylquinazolin-2-yl)-3-fluorophenol

Product 1

HCID 1361214163-Fluoro-2-(7-methyl-4-(piperazin-1-yl)quinazolin-2-yl)phenolYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

2-(4-Chloro-7-methylquinazolin-2-yl)-3-fluorophenol (4.37 g, 15.14 mmol) was suspended in CH2Cl2 (65 mL) under an N2 atmosphere and placed into an ice water bath. To this solution was added a solution of piperazine (4.00 g, 45.42 mmol) and triethylamine (4.2 mL, 30.28 mmol) in CH2Cl2 (15 mL) in one portion. After stirring the reaction for 30 minutes, it was partitioned between CH2Cl2 and H2O and separated, and the aqueous layer was extracted twice more with CH2Cl2. The organic phase was dried over Na2SO4, filtered, and concentrated to a bright yellow solid which was purified via silica gel chromatography using a 95%/5% mixture of CH2Cl2/MeOH to afford 3-fluoro-2-(7-methyl-4-(piperazin-1-yl)quinazolin-2-yl)phenol (4.32 g, 85%) as a bright yellow solid. LC/MS: m/z 339.3 (M+H)+ at 1.80 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

  1. customplaced into an ice water bath
  2. customthe reaction for 30 minutes
  3. customit was partitioned between CH2Cl2 and H2O
  4. customseparated
  5. extractionthe aqueous layer was extracted twice more with CH2Cl2
  6. dry with materialThe organic phase was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated to a bright yellow solid which
  9. customwas purified via silica gel chromatography

Sources & evidence

ORD record
ord-8188d17d7bbe409788e4f12b30dd57ae
Source dataset
uspto-grants-2012_10
Patent number
US08283354B2

Reaction notes

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