5-Methoxy-6-(4-methyl-1H-imidazol-1-yl)pyridin-3-amine synthesis

Yield:1079178-13-4 83%

Reaction Conditions:

with iron;acetic acid at 50; for 1 h;Inert atmosphere;

Steps:

15 Synthesis of 5-methoxy-6-(4-methyl-lH-imidazol-l-yl) pyridin-3-amine

Synthesis of 5-methoxy-6-(4-methyl-lH-imidazol-l-yl) pyridin-3-amine [0329] To a stirred solution of 3-methoxy-2-(4-methyl-lH-imidazol-l-yl)-5-nitropyridine (1.8 g, 7.69 mmol) in acetic acid (18 mL) under argon atmosphere was added iron powder (4.3 g, 7.69 mmol) at RT. The reaction mixture was stirred at 50 °C for 1 h. After consumption of the starting materials (monitored by TLC), the reaction was diluted with a saturated sodium bicarbonate solution (50 mL) and extracted with 10% MeOH:CH₂Cl₂ (2 x 50 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo to afford 5-methoxy-6-(4-methyl-lH-imidazol-l-yl) pyridin-3 -amine (1.3 g, 83%) as a brown solid. 1H-NMR (DMSO-<, 500 MHz): δ 7.83 (s, 1H), 7.37 (s, 1H), 7.20 (s, 1H), 6.78 (s, 1H), 5.57-5.53 (m, 2H), 3.79 (s, 3H), 2.16 (s, 3H); LC-MS: 205 (M+l); (column; Eclipse XDB C-18 (150 4.6 mm, 5 μπι); RT 5.69 min. 0.05% aq TFA: ACN; 1.0 mL/min); UPLC (column; Acquity UPLC HSS T3 2.1 X 100 mm, 1.8 μιη); RT 2.93 min. ACN: 0.025% TFA (Aq); 0.30 mL/min. TLC: 5% MeOH:CH₂Cl₂ (R 0.4).

References:

WO2015/66697,2015,A1 Location in patent:Paragraph 0329