2.50 g (1 1.4 mmol) of 6,7-dimethoxy-2-methylquinazolin-4-ol were suspended in 1 1.00 mL of thionyl chloride, admixed with 10 drops of N,N-dimethylformamide and stirred for 1 h at 80°C. The thionyl chloride was removed in vacuo. The residue was admixed twice with in each case 20 mL of toluene and evaporated to dryness in vacuo. With ice bath cooling, 20 mL of a 5N sodium hydroxide solution were added dropwise to the residue. The suspension was admixed with 20 mL of dichloromethane and vigorously stirred for 10 min. The phases were separated and the aqueous phase was extracted by shaking five times with in each case 20 mL of dichloromethane. The combined organic phases were dried over sodium sulphate, filtered and evaporated to dryness in vacuo. 2.71 g (100percent of theory) of the title compound were isolated as a beige solid. 1H-NMR (400 MHz, CDCI3): δ [ppm] = 2.79 (s, 3H), 4.04 (s, 3H), 4.05 (s, 3H), 7.25 (s, 1H), 7.35 (s, 1H). LC-MS (method 1): Rt = 3.19 min; MS (ESI/APCIpos) m/z = 239.1 [M+H]
Step b 4-Chloro-6,7-dimethoxy-2-methylquinazoline A mixture of 6,7-dimethoxy-2-methylquinazolin-4(3H)-one (1.0 mg) and phosphorous oxychloride (20 mL) was refluxed for 3 h. The reaction mixture was attained to rt and poured into ice cold water and stirred for 10 min. The solution was extracted with chloroform (3*100 mL) and the combined CHCl3 layer was washed water, brine and dried over sodium sulfate. The solution was filtered and evaporated the solvent to give the product as a yellow color solid (1.0 g, 92percent), mp 182-184° C. 1H NMR (400 MHz, CDCl3): δ 7.36 (1H, s), 7.30 (1H, s), 4.06 (6H, s), 2.81 (3H, s); LC-MS (positive ion mode): m/z 239, 241 (M+H)+.
Reference：
[1] Patent: US2013/266563, 2013, A1, . Location in patent: Paragraph 0327
[2] Synthesis, 2004, # 3, p. 429 - 435
[3] Journal of Medicinal Chemistry, 1996, vol. 39, # 1, p. 267 - 276
[4] ChemMedChem, 2014, vol. 9, # 7, p. 1476 - 1487
N-[1-(5-bromothiophen-2-yl)ethyl]-6,7-dimethoxy-2-methylquinazolin-4-amine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With N-ethyl-N,N-diisopropylamine; In dimethyl sulfoxide; at 130.0℃; for 6.0h;Microwave irradiation;
To a microwave vial were added 4-chloro-6,7-dimethoxy-2-methylquinazoline (commercially available; 2.39 g, 10.0 mmol), 1 -(5-bromothiophen-2-yl)ethanamine (described in procedure INT-28; 2.27 g, 1 1.0 mmol), N,N-diisopropylethylamine (4.5 ml_, 26 mmol) and DMSO (20 ml_). The reaction mixture was heated to 130C during 6 hours in the microwave. The mixture was added to H2O, extracted with DCM and the solvent removed in vacuo. The residue was stirred in Et.20 during 20 minutes then filtered to give the title compound as a beige solid (3.00 g, 73%). 1H-NMR (400 MHz, DMSO-de): delta [ppm] = 8.09 (d, 1H), 7.60 (s, 1H), 7.06 (d, 1H), 7.05 (s, 1H), 6.92 (dd, 1H), 5.78 (quin, 1H), 3.87 (d, 6H), 2.43 (s, 3H), 1.66 (d, 3H). LC-MS (method 7): m/z: [M+H]+ = 408, Rt = 0.91 min.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
Life Science
For Research Only
80K+ Compounds
Competitive Price
1-2 Day Shipping
