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CAS No. : | 827-24-7 | MDL No. : | MFCD00209452 |
Formula : | C7H7BrN2O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | VFPKZASVVCBVMG-UHFFFAOYSA-N |
M.W : | 231.05 | Pubchem ID : | 2775306 |
Synonyms : |
|
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With ammonia hydrochloride; zinc powder; In tetrahydrofuran; methanol; at 40℃; for 1.0h; | 2-bromo-4-methyl-6-nitroaniline (5.00 g, 21.64 mmol) was dissolved in MeOH(148 mL) and THF (18.50 mL). Ammonium chloride (23.15 g, 433 mmol) then zinc (14.15 g, 216 mmol) were added and the reaction mixture was heated to 40 C for lh. The reaction mixture was cooled to ambient temperature, concentrated in vacuo, re-dissolved in EtOAc and saturated Na2CO3, and stirred vigorously for 10 minutes. The mixture was filtered through a sintered glass funnel and washed with more EtOAc. Theorganic layer was further washed twice with water, washed with brine, dried with sodium sulfate, filtered, and concentrated in vacuo to yield Intermediate I-iSA (4.35 g, 21.63 mmol, 100 % yield). ‘H NMR (400MHz, CHLOROFORM-d) 6.81 (s, 1H), 6.48 (s, 1H), 3.66 (br. s., 2H), 3.46 (br. s., 2H), 2.19 (s, 3H). LC-MS: method H, RT = 0.93 mm, MS (ESI) m/z: 201.0 (M+H) |
100% | With ammonia hydrochloride; zinc powder; In tetrahydrofuran; methanol; at 40℃; for 1.0h; | 2-bromo-4-methyl-6-nitroaniline (5.00 g, 21.64 mmol) was dissolved in MeOH (148 mL) and THF (18.50 mL). Ammonium chloride (23.15 g, 433 mmol) then zinc (14.15 g, 216 mmol) were added and the reaction mixture was heated to 40 C for lh. The reaction mixture was cooled to ambient temperature, concentrated in vacuo, re-dissolved in EtOAc and saturated Na2CO3, and stirred vigorously for 10 minutes. Themixture was filtered through a sintered glass funnel and washed with more EtOAc. The organic layer was further washed twice with water, washed with brine, dried with sodium sulfate, filtered, and concentrated in vacuo to yield Intermediate I-iSA (4.35 g, 21.63 mmol, 100 % yield). ‘H NMR (400MHz, CHLOROFORM-d) 6.81 (s, 1H), 6.48 (s, 1H), 3.66 (br. s., 2H), 3.46 (br. s., 2H), 2.19 (s, 3H). LC-MS: method H, RT = 0.93 mm,MS (ESI) m/z: 201.0 (M+H) |
97% | With hydrogenchloride; stannous chloride; In ethanol; water monomer; at 60℃; for 3.0h;Inert atmosphere; | To a solution of Example 35a (20.0 g, 86.6 mmol, 1.0 eq) in EtOH (120 mL) and conc. HCl (40 mL) was added SnCl2 (97.4 g, 433 mmol, 5.0 eq). The reaction mixture was stirred at 60C for 3 h under N2. After cooled to room temperature, the mixture was poured into 2M NaOH aqueous solution (750 mL) at 0C. DCM (800 mL) was added to the mixture, and the white solid was removed by filtration. The organic layer was separated, and the aqueous phase was extracted with DCM (500 mL*2). The combined organic extracts were washed with brine, dried over Na2SO4, and concentrated. The crude was purified by silica gel flash column chromatography to afford the product Example 35b (16.8 g, 97% yield) as a yellow solid. LCMS [M+1]+ = 201.2. |
67% | With hydrogenchloride; stannous chloride; In ethanol; water monomer; at 60℃; for 3.0h;Inert atmosphere; | To a solution of Intermediate la (84 g, 363.6 mmol) in EtOH (464 m ) and cone. HC1 (116 m ) was added SnCL (408g, 2.16 mol). The reaction mixture was stirred at 60C for 3 h under N2. After cooled to room temperature, the mixture was poured into 2M NaOH aqueous solution (750 mb) to pH = 12 at 0C. DCM (800 mb) was added to the mixture, and the white solid was removed by filtration. The organic layer was separated, and the aqueous phase was extracted with DCM (500 mb*2). The combined organic extracts were washed with brine, dried over Na2SC>4, and concentrated. The crude was purified by silica gel flash column chromatography (Petroleum Ether/EtOAc = 2/1) to afford the product Intermediate lb (49 g, 67% yield) as a yellow solid. ECMS [M+l] + = 201.2. |
67% | With hydrogenchloride; stannous chloride; In ethanol; water monomer; at 60℃; for 3.0h;Inert atmosphere; | To a solution of Intermediate la (84 g, 363.6 mmol) in EtOH (464 m ) and cone. HC1 (116 m ) was added SnCL (408g, 2.16 mol). The reaction mixture was stirred at 60C for 3 h under N2. After cooled to room temperature, the mixture was poured into 2M NaOH aqueous solution (750 mb) to pH = 12 at 0C. DCM (800 mb) was added to the mixture, and the white solid was removed by filtration. The organic layer was separated, and the aqueous phase was extracted with DCM (500 mb*2). The combined organic extracts were washed with brine, dried over Na2SC>4, and concentrated. The crude was purified by silica gel flash column chromatography (Petroleum Ether/EtOAc = 2/1) to afford the product Intermediate lb (49 g, 67% yield) as a yellow solid. ECMS [M+l] + = 201.2. |
35% | With hydrogenchloride; tin(II) chloride dihydrochloride; In ethanol; at 60℃; for 4.0h;Inert atmosphere; | In argon atmosphere, to an EtOH solution (100 mL) of commercially available 2-bromo-4-methyl-6-nitroaniline (5 g, 21.6 mmol) was added Tin(II) chloride dehydrate (16 g, 84.4 mmol) in small portions, followed by c.HCl (12 mL) dropwise over 10 min. The mixture was stirred at 60C for 4 h. On completion, the mixture was quenched with saturated NaHCO3 aqueous (50 mL) carefully, extracted with EA (3 × 50 mL). The combined organic layer was washed with brine, dried with anhydrous Na2SO4, evaporated at reduced pressure to give title compound as a red solid in 35% yield. 1H NMR (300 MHz, Chloroform-d) δ 6.51 (s, 1H), 6.38 (s, 1H), 4.26 (broad s, 4H), 2.07 (s, 3H). |
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