New discoveries in chemical research and development in 2021. The transformation of simple hydrocarbons into more complex and valuable products via catalytic C–H bond functionalisation has revolutionised modern synthetic chemistry. 7170-01-6, name is 3-Methyl-1H-1,2,4-triazole belongs to triazoles compound, it is a common compound, a new synthetic route is introduced below. 7170-01-6
To a mixture of 3-methyl- lH- l,2,4-triazole (330 mg, 3.97 mmol), 5-chloro-2-fluoro- benzaldehyde (425 mg, 2.68 mmol) in DMSO (5.0 mL) is added K2C03 (725 mg, 5.25 mmol). The reaction mixture is stirred at 100 C for 2 hours. The reaction mixture is allowed to cool to room temperature, diluted with CH2C12 (100 mL), and washed with H20 (75 mL x2). The organic layer is dried with Na2S04 and filtered. The filtrate is concentrated under reduced pressure and the residue is purified by silica gel flash column chromatography with 5% MeOH in EtOAc as the eluent to afford an impure mixture of 5-chloro-2-(3-methyl- l,2,4-triazol-l-yl)-benzaldehyde plus regiosiomer (270 mg).To a mixture of 4-(2-amino-pyrimidin-5-yl)-Nl-ieri-butyl-benzene-l,2-diamine (270 mg, 1.05 mmol) and impure mixture of 5-chloro-2-(3-methyl- l,2,4-triazol-l-yl)-benzaldehyde plus regiosiomer (270 mg) in DMF (15.0 mL) is added Oxone (650 mg, 1.06 mmol) in H20 (5.0 mL). The reaction mixture is stirred at room temperature for 1.5 hours and then quenched with saturated sodium thiosulfate aq. (25 mL). The quenched reaction mixture is extracted with EtOAc (25 mL x2) and the combined organic layers are washed with H20 (50 mL x2), dried with Na2S04 and filtered. The filtrate is concentrated under reduced pressure and the residue is purified by silica gel flash column chromatography with 5% MeOH in CH2C12 as the eluent to afford an impure mixture of 5-(2-amino- pyrimidin-5-yl)- l-ieri-butyl-2-[5-chloro-2-(3-methyl- l,2,4-triazol-l-yl)-phenyl]-2,3- dihydro-lH-benzimidazol-2-ol plus regiosiomer (25 mg).I l l A mixture of 5-(2-amino-pyrimidin-5-yl)- l-ieri-butyl-2-[5-chloro-2-(3-methyl- l,2,4- triazol-l-yl)-phenyl]-2,3-dihydro-lH-benzimidazol-2-ol plus regiosiomer (25 mg) in MeOH (25 mL) is heated at 70 C for 16 hours. The reaction mixture is allowed to cool to room temperature and is concentrated under reduced pressure. The residue is purified by silica gel flash column chromatography with 5% MeOH in CH2CI2 as the eluent followed by further purification using a HPLC C- 18 column with CH3CN (0.1%TFA) in H20 (0.1%TFA) as the eluent to afford 5-{ l-ieri-butyl-2-[5-chloro-2-(3-methyl- l,2,4- triazol-l-yl)-phenyl]-lH-benzimidazol-5-yl}-pyrimidin-2-ylamine (Example 37) (9 mg, 37 %) as a white solid LCMS (ESMS): m/z 459.20 (M++l) and 5-{ l-ieri-butyl-2-[5- chloro-2-(5-methyl-l,2,4-triazol- l-yl)-phenyl]- lH-benzimidazol-5-yl}-pyrimidin-2- ylamine (Example 38) (6 mg, 25 %) as a white solid. LCMS (ESMS): m/z 459.20 (M++l)
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Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; CHEN, Zhidong; HAO, Ming-Hong; LIU, Weimin; LO, Ho-Yin; LOKE, Pui Leng; MAN, Chuk, Chui; MORWICK, Tina, Marie; NEMOTO, Peter, Allen; TAKAHASHI, Hidenori; TYE, Heather; WU, Lifen; WO2011/68821; (2011); A1;,
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