ChemicalBook CAS DataBase List 8-BROMO-2-CHLOROQUINAZOLINE

8-BROMO-2-CHLOROQUINAZOLINE synthesis

5synthesis methods

Product Name:8-BROMO-2-CHLOROQUINAZOLINE
CAS Number:956100-63-3
Molecular formula:C8H4BrClN2
Molecular Weight:243.49

956100-62-2

956100-63-3

General procedure for the synthesis of 8-bromo-2-chloroquinazoline from 4-amino-8-bromo-2-chloroquinazoline: 8-bromo-2-chloroquinazolin-4-amine (12.93 g, 50 mmol) was dissolved in THF (500 mL) under stirring conditions, and isoamyl nitrite (23.43 g, 200 mmol) was added slowly dropwise over a dropwise period of 3 hours. Subsequently, the reaction mixture was continued to be stirred at 60 °C for 40 min. Upon completion of the reaction, the progress of the reaction was monitored by TLC (unfolding agent: PE:EA = 1:1). When the reaction was complete, the mixture was cooled to room temperature and the solvent was removed by distillation under reduced pressure. The residue was dissolved in DCM (300 mL) and the organic layer was washed sequentially with brine (100 mL) and water (100 mL). The organic layer was dried over anhydrous Na2SO4 and purified by column chromatography (eluent: DCM:PE = 1:1) to afford the target compound 8-bromo-2-chloroquinazoline as a yellow solid (8.21 g, 67% yield).1H NMR (DMSO-d6, 400 MHz): δ 9.66 (s, 1H), 8.45 (dd, J = 0.8, 7.6 Hz, 1H), 8.26 (dd, J = 0.8, 8.0 Hz, 1H), 7.73 (dd, J = 7.6, 8.0 Hz, 1H).

956100-62-2 Synthesis

956100-62-2
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$27.00/1g

956100-63-3
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$55.00/250mg

Yield: 67%

Reaction Conditions:

with isopentyl nitrite in tetrahydrofuran at 60; for 8.67 h;

Steps:

L; 195d
To a stirred mixture of 8-bromo-2-chloroquinazolin-4-amine (12.93 g, 50 mmol) in THF (500 mL) was added isoamyl nitrite (23.43 g, 200 mmol) over 3 hours and 40 mins at 6O⁰C. The mixture was stirred for another 5 hours. TLC (PE:EA,1 :1) showed reaction complete. After cooling to room temperature, the solvent was stripped and the residue was taken into DCM (300 mL). The organic layer was washed with brine (100 mL), water (100 mL), then dried over anhydrous Na₂SO₄ and purified by chromatography (DCM:PE, 1:1) to give the title compound as a yellow solid ( 8.21 g, 67%). 1 HNMR (DMSOd₆, 400 MHz): δ 9.66 (s, 1 H), 8.45 (dd, J = 0.8, 7.6 Hz, 1 H), 8.26 (dd, J = 0.8, 8.0 Hz, 7.73 (dd, J = 7.6, 8.0 Hz, 1 H).

References:

PFIZER PRODUCTS INC. WO2007/125405, 2007, A2 Location in patent:Page/Page column 25; 81-82