* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Reference:
[1] Journal of the Indian Chemical Society, 1984, vol. 61, # 11;12, p. 1053 - 1056
[2] Patent: WO2016/16421, 2016, A1, . Location in patent: Page/Page column 59
With hydrogenchloride; iron; In methanol; at 8 - 16℃; for 16.0h;
General procedure for the synthesis of U2To a stirred solution of Ui in MeOH (100 mL) were added concentrated HC1 (9 mL, 108 mmol, 1 2M) and iron powder (10.0 g, 179 mmol). The reaction mixture was stirred at 8-16C for 16 hours. After reaction was completed, the mixture was filtered. The filtrate was neutralized to pH 8 with NaHCO3 aqueous solution and filtered. The filtrate was extracted with EtOAc (100 mLx2). The combined extracts were washed with brine (200 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford U2.
6-bromo-4-chloro-1H-benzo[d]imidazol-2(3H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
76%
In chloroform; at 60℃; for 12.0h;Inert atmosphere;
To a solution of <strong>[16429-44-0]5-bromo-3-chlorobenzene-1,2-diamine</strong> (200 mg,0.90 mmol)inchloroform (3 mL)was added di(1H-imidazol-1-yl)methanone (220 mg,1.35 mmol). The mixture was heated to 60 C for 12 h under a nitrogen atmosphere. After cooling the reaction toroom temperature,the white precipitate was filtered off,washed with chloroform (3 mL x 2),and dried in vacuo to give the title compound (170 mg,76%)as a white solid. 1H NMR (400MHz,DMSO-d6)8 11.35 (s,1H),11.05 (s,1H),7.21 (d,J = 1.6 Hz,1H),7. 04 (d,J = 1.6 Hz,1H).
In tetrahydrofuran; for 16.0h;Reflux;
General procedure for the synthesis of U3A mixture of U2 (7.2 g, 32.5 mmol) and CDI (6.32 g, 39.0 mmol) in anhydrous THF (100 mL) was refluxed for 16 hours. After cooling to room temperature, the white precipitate was collected by filtration and dried under reduced pressure to afford U3.
Step 1 : Into a 30 niL vial were charged 5-broino-3-chlorobenzene-l,2- diamine (1.0 equiv), ytterbium (III) trifluoromethanesulfonate (0.1 equiv.) and 1 ,1,1- trimethoxyethane (1.2 equiv.). The mixture was heated at 90 C for 1 h and cooled to room temperature and concentrated in vacuo. The residue was purified by flash chromatography (0-5% MeOH/DCM) to afford 5-broroo-7-chloro-2-methyl-l H-benzo[d]imidazole in 100% yield as a yellow solid. LCMS (m/z) (M+H) = 247.0, 0.81 mm
5-Bromo-3-chloro-1 ,2-diaminobenzene (4.6 g; 20 mmol; 1 eq.) is dissolved in EtOH (200 mL) and 2,3-dixydroxy-1 ,4-dioxane (2.5 g, 20 mmol; 1 eq.) is added. The mixture is stirred for 4 h at room temperature and a second portion of 2,3-dihydroxy-1 ,4-dioxane (1.3 g; 10 mmol; 0.5 eq.) is added. After stirring for 24 h at room temperature, the reaction mixture is concentrated and the residue is purified by FCC (EtOAc gradient in hexane) to provide 7- bromo-5-chloroquinoxaline as a beige solid (4.7 g; yield: 92%; UPLC purity: 98%).
92%
In ethanol; at 20℃; for 28.0h;
5-bromo-3-chloro-1 ,2-diaminobenzene (4.6 g; 20 mmol; 1 .0 eq.) was dissolved in EtOH (200 ml_) and then 2,3-dihydroxy-1 ,4-dioxane (2.5 g, 20 mmol; 1 .0 eq.) was added. The mixture was stirred for 4 h at RT and a second portion of 2,3-dihydroxy-1 ,4-dioxane (1 .3 g; 10 mmol; 0.5 eq.) was added. After stirring for 24 h at rt, RM was concentrated in a rotary evaporator and the residue was purified by FCC to provide 7-bromo-5- chloroquinoxaline (Intermediate 3) as a beige solid (4.7 g; yield 92 %; 98 % by UPLC).
5-bromo-7-chloro-1H-benzimidazole A solution of <strong>[16429-44-0]5-bromo-3-chlorobenzene-1,2-diamine</strong> (2 g, 9.03 mmol) in formic acid (30 ml) was heated at reflux for 16 hours. The reaction progress was monitored by LCMS. Reaction mixture was concentrated under vacuum to yield brown oil. The mixture was extracted by EtOAc from a saturated aqueous solution of NaHCO3, dried over MgSO4 and evaporated under vacuum to yield 5-bromo-7-chloro-1H-benzo[d]imidazole as a pale yellow solid. Mass spectrum (EI, m/z): Calculated for C7H4BrClN2, 232.5 (M+H), found 233.0.
for 16.0h;Reflux;
5-bromo-7-chloro-1H-benzimidazole A solution of <strong>[16429-44-0]5-bromo-3-chlorobenzene-1,2-diamine</strong> (2 g, 9.03 mmol) in formic acid (30 ml) was heated at reflux for 16 hours. The reaction progress was monitored by LCMS. Reaction mixture was concentrated under vacuum to yield brown oil. The mixture was extracted by EtOAc from a saturated aqueous solution of NaHCO3, dried over MgSO4 and evaporated under vacuum to yield 5-bromo-7-chloro-1H-benzo[d]imidazole as a pale yellow solid. Mass spectrum (EI, m/z): Calculated for C7H4BrClN2, 232.5 (M+H), found 233.0.
for 16.0h;Reflux;
5-bromo-7-chloro-1H-benzimidazole A solution of <strong>[16429-44-0]5-bromo-3-chlorobenzene-1,2-diamine</strong> (2 g, 9.03 mmol) in formic acid (30 ml) was heated at reflux for 16 hours. The reaction progress was monitored by LCMS. Reaction mixture was concentrated under vacuum to yield brown oil. The mixture was extracted by EtOAc from a saturated aqueous solution of NaHCO3, dried over MgSO4 and evaporated under vacuum to yield 5-bromo-7-chloro-1H-benzo[d]imidazole as a pale yellow solid. Mass spectrum (EI, m/z): Calculated for C7H4BrClN2, 232.5 (M+H), found 233.0.