Application of 18437-58-6 , The common heterocyclic compound, 18437-58-6, name is 4-Amino-2-picoline, molecular formula is C6H8N2, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.
Compound 36: 7-Fluoro-1 -methyl-N-(2-methyl-4-pyridinyl)-4H-imidazor5,1 – ciri ,41benzothiazine-3-carboxamideTo a solution of 4-amino-2-methylpyridine (74.8 mg, 0.692 mmol) in dry 1 ,4-dioxane (1 mL) stirred at room temperature under argon was added trimethylaluminium (2 M in heptanes) (0.346 mL, 0.692 mmol) dropwise and the reaction mixture was stirred for 1 hour. (7-Fluoro-1-methyl-4H-imidazo[5,1-c][1 ,4]benzothiazin-3-yl)carbonyl 2- methylpropyl carbonate (intermediate 67, 36 mg, 0.099 mmol) in dry 1 ,4-dioxane (1 mL) was added dropwise and the mixture was stirred at 80 C for 4 hours. The reaction mixture was cooled to room temperature, quenched with water and extracted with DCM. 1 M NaOH was added in order to separate phases. The organic layers were washed with 0.1 M HCI, then dried using a phase separator filter tube and concentrated under reduced pressure to give a residue which contained the title compound with some impurities. The retained aqueous phase was basified with 1 M NaOH and extracted with DCM. The organic layer was dried using a phase separator filter tube and concentrated under reduced pressure to give a residue containing the title compound together with some impurities. This residue was dissolved in DCM, 1 M HCI was added and mixture stirred vigorously for 1 hour. The layers were separated and the water layer basified with 1 M NaOH. The mixture was was extracted with DCM and the organic layer dried using a phase separator filter tube and concentrated under reduced pressure to give the title compound of >90% purity (by NMR). This 90% pure material was further purified. The residue was dissolved in DCM, water was added and mixture stirred vigorously for 1 hour. The organic layer was dried using a phase separator filter tube and concentrated under reduced pressure to give the title compound after washing with diethyl ether; 1H NMR (500 MHz, CHLOROFORM-d): delta ppm 2.56 (s, 3 H) 2.66 (s, 3 H) 4.41 (s, 2 H) 7.05 – 7.10 (m, 1 H) 7.30 (dd, J=8.16, 2.82 Hz, 1 H) 7.41 (dd, J=5.57, 1.91 Hz, 1 H) 7.50 (dd, J=8.93, 4.81 Hz, 1 H) 7.56 (d, J=1 .68 Hz, 1 H) 8.41 (d, J=5.65 Hz, 1 H) 9.04 (s, 1 H); MS (m/z): 355 [MH]+.
The synthetic route of 18437-58-6 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; GLAXO GROUP LIMITED; BERTANI, Barbara; CREMONESI, Susanna; GARZYA, Vincenzo; MICHELI, Fabrizio; RUPCIC, Renata; SABBATINI, Fabio Maria; WO2011/151361; (2011); A1;,
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