Reaktion #1009591

Reaktionsgleichung

tert-butyl 4-(3-chloro-5-formylphenyl)piperazine-1-carboxylate

tert-Butyl 4-(3-Chloro-5-formylphenyl)piperazine-1-carboxylate

2-amino-4,6-dimethoxybenzamide

p-TsOH

NaHSO3

trifluoroacetic acid

→

title compound

Ausbeute 29.3%

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

Ausbeute 29.3%

Lösungsmittel

DMA

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe reaction mixture was cooled to room temperature
2. 2
   Temperaturthe mixture was heated at 70° C. for 1 h
3. 3
   TemperaturThe reaction mixture was cooled to room temperature
4. 4
   Einengenconcentrated
5. 5
   SonstigeThe residue was purified by silica gel chromatography
6. 6
   Wascheneluting with 0-100% 92:7:1 CHCl3/MeOH/concentrated NH4OH in CH2Cl2
7. 7
   SonstigeThis material was further purified by reverse phase HPLC
8. 8
   Wascheneluting with 10% to 90% CH3CN in H2O with 0.1% TFA
9. 9
   EinengenThe product fractions were concentrated
10. 10
    workup.DISSOLUTIONthe residue was dissolved in acetonitrile
11. 11
    Filtrationthe precipitate filtered
12. 12
    Waschenwashed with water
13. 13
    Sonstigedried under vacuum

Vorschrift

A solution of tert-butyl 4-(3-chloro-5-formylphenyl)piperazine-1-carboxylate (3, 0.300 g, 0.918 mmol) and 2-amino-4,6-dimethoxybenzamide (4, 0.120 g, 0.612 mmol) in DMA (4 mL) was treated with p-TsOH (0.424 g, 1.46 mmol) and NaHSO3 (0.290 g, 1.84 mmol) and then heated at 110° C. for 16 h. The reaction mixture was cooled to room temperature, trifluoroacetic acid (5 mL) was added and the mixture was heated at 70° C. for 1 h. The reaction mixture was cooled to room temperature and concentrated. The residue was purified by silica gel chromatography eluting with 0-100% 92:7:1 CHCl3/MeOH/concentrated NH4OH in CH2Cl2. This material was further purified by reverse phase HPLC eluting with 10% to 90% CH3CN in H2O with 0.1% TFA. The product fractions were concentrated and the residue was dissolved in acetonitrile and water. The mixture was basified with concentrated NH4OH and the precipitate filtered, washed with water, and dried under vacuum to afford the title compound (0.072 g, 29%) as an off-white solid: 1H NMR (500 MHz, DMSO-d6) δ 7.60-7.70 (m, 2H), 7.08-7.12 (m, 1H), 6.78 (d, J=2.3 Hz, 1H), 6.55 (d, J=2.3 Hz, 1H), 3.89 (s, 3H), 3.85 (s, 3H), 3.24 (t, J=5.2 Hz, 4H), 3.28 (t, J=5.2 Hz, 4H); ESI MS m/z 401 [M+H]+.

Quelle