2-Bromoethanol → 2-(4-(4-(2-hydroxyethyl)piperazin-1-yl)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one

HRID 591586Notes

Reaction equation

HRID 591586 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[C:11]([O:13][CH3:14])[CH:10]=[C:9]2[C:4]=1[C:5](=[O:27])[NH:6][C:7]([C:15]1[CH:20]=[CH:19][C:18]([N:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)=[CH:17][CH:16]=1)=[N:8]2.C(=O)([O-])[O-].[K+].[K+].Br[CH2:35][CH2:36][OH:37]>CN(C=O)C.O>[OH:37][CH2:36][CH2:35][N:24]1[CH2:23][CH2:22][N:21]([C:18]2[CH:19]=[CH:20][C:15]([C:7]3[NH:6][C:5](=[O:27])[C:4]4[C:9](=[CH:10][C:11]([O:13][CH3:14])=[CH:12][C:3]=4[O:2][CH3:1])[N:8]=3)=[CH:16][CH:17]=2)[CH2:26][CH2:25]1

Participants

6

Reactant 3

HCID 108982-BromoethanolHCID 11430Potassium CarbonateHCID 1359390885,7-dimethoxy-2-(4-(piperazin-1-yl)phenyl)quinazolin-4(3H)-one

Product 1

HCID 1359391212-(4-(4-(2-hydroxyethyl)piperazin-1-yl)phenyl)-5,7-dimethoxyquinazolin-4(3H)-oneYield 9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 5,7-dimethoxy-2-(4-(piperazin-1-yl)phenyl)quinazolin-4(3H)-one (1) (0.68 mmol) in DMF (8 mL) was added potassium carbonate (0.68 mmol) and 2-bromoethanol (0.68 mmol). The resulting solution was stirred at room temperature overnight. Then, the mixture was diluted with water, extracted with EtOAc, washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to afford 2. The material was purified by flash chromatography on silica gel, eluting with 50% to 100% of 92:7:1 CHCl3/MeOH/concentrated NH4OH in CH2Cl2. The product was further purified by reverse-phase chromatography, eluting with 10% to 90% CH3CN in H2O, to afford the title compound (0.025 g, 9%). 1H NMR (300 MHz, DMSO-d6): δ 11.45 (s, 1H), 8.08 (d, J=8.9 Hz, 2H), 7.00 (d, J=9.1 Hz, 2H), 6.68 (s, 1H), 6.46 (s, 1H), 4.30-4.55 (m, 1H), 3.88 (s, 3H), 3.83 (s, 3H), 3.43-3.67 (m, 2H), 3.10-3.43 (m, 7H), 2.77-3.04 (m, 1H), 2.31-2.64 (m, 2H). ESI MS m/z 411 [M+H]+.

Workup

  1. extractionextracted with EtOAc
  2. washwashed with brine
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto afford 2
  7. customThe material was purified by flash chromatography on silica gel
  8. washeluting with 50% to 100% of 92:7:1 CHCl3/MeOH/concentrated NH4OH in CH2Cl2
  9. customThe product was further purified by reverse-phase chromatography
  10. washeluting with 10% to 90% CH3CN in H2O

Sources & evidence

ORD record
ord-1cbe613bb99649c2904738b6864c6cf5
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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