تفاعل #168405
ord-989f487bd63e4a6bb14891cb7913a9a9
معادلة التفاعل
المتفاعلات
الكواشف
المذيبات
ظروف التفاعل
المعالجة
- 1أخرىThe reaction mixture was quenched with sat. aqueous ammonium chloride
- 2استخلاصextracted with ethyl acetate
- 3تجفيفThe organic layer was dried over sodium sulfate
- 4ترشيحfiltered
- 5تركيزconcentrated
- 6أخرىThe residue was purified by silica gel chromatography (hexanes/0-50% EtOAc)
الإجراء التجريبي
To a solution of 4-(5-chloropyridin-3-yl)-2-(hydroxy(phenyl)methyl)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile (276 mg, 0.585 mmol) in NMP (3 mL) was added lithium hydroxide (28.0 mg, 1.170 mmol) and iodoethane (142 μL, 1.754 mmol), and the reaction mixture was allowed to stir at room temperature overnight. The reaction mixture was quenched with sat. aqueous ammonium chloride and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography (hexanes/0-50% EtOAc) to afford racemic 4-(5-chloropyridin-3-yl)-2-(ethoxy(phenyl)methyl)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile. The racemic material was then purified by chiral supercritical fluid chromatography (Chiralpak OJ-H, 21×250 mm, MeOH in CO2) to afford 4-(5-chloropyridin-3-yl)-2-((R)-ethoxy(phenyl)methyl)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile and 4-(5-chloropyridin-3-yl)-2-(S)-ethoxy(phenyl)methyl)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ESI calc'd. for C29H30ClN5O [M+H]+ 500. found 500. 1H NMR (600 MHz, CD3OD) δ 8.75 (d, J=2.3, 1H), 8.70 (d, J=1.6, 1H), 8.27 (s, 1H), 8.23 (t, J=2.0, 1H), 7.49 (d, J=7.2, 2H), 7.38 (t, J=7.3, 2H), 7.36-7.31 (m, 1H), 5.94 (s, 1H), 4.01-3.85 (m, 2H), 3.68-3.59 (m, 2H), 1.44-1.36 (m, 2H), 1.27 (t, J=7.0, 3H), 1.07-0.98 (m, 1H), 0.89-0.78 (m, 1H), 0.76-0.66 (m, 5H), 0.64-0.54 (m, 1H), 0.54-0.46 (m, 1H), 0.46-0.36 (m, 2H).