Structure of 867267-28-5
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CAS No. : | 867267-28-5 |
Formula : | C7H7NO3 |
M.W : | 153.14 |
SMILES Code : | O=CC1=C(O)C=NC(OC)=C1 |
MDL No. : | MFCD13189872 |
InChI Key : | GRJJLRLFOQLVKR-UHFFFAOYSA-N |
Pubchem ID : | 72212498 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H312-H332 |
Precautionary Statements: | P261-P264-P270-P271-P280-P302+P352-P304+P340-P305+P351+P338-P312-P330-P362-P403+P233-P501 |
* 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 |
---|---|---|
55% | With hydrogenchloride; In tetrahydrofuran; water; at 50℃; for 0.5h; | Step 3 ;To a solution of 2-methoxy-5-(methoxymethoxy)isonicotinaldehyde (10 g, 0.05 mol) in THF (100 mL) was added 3 N HCl (150 mL). The reaction was stirred at 50 C. for 30 min, cooled to rt, and diluted with water (100 mL). The mixture was neutralized to pH 7-8 and extracted with EtOAc (200 mL) three times. The organic layer was dried over Na2SO4 and concentrated to give 5-hydroxy-2-methoxyisonicotinaldehyde (4.2 g, 55%) as a yellow solid. 1H NMR (400 MHz; DMSO) δ=10.31 (s, 1H), 8.03 (s, 1H), 6.89 (s, 1H), 3.80 (s, 3H). |
With hydrogenchloride; In tetrahydrofuran; at 50℃; for 0.5h; | [0172] To a solution of 2-methoxy-5-(methoxymethoxy)isonicotinaldehyde (10 g, 0.05 mol) in THF (100 mL) was added 3 N HC1 (150 mL). The reaction was stirred at 50 C for 30 mm, cooled to rt, and diluted with water (100 mL). The mixture was neutralized to pH 7-8 and extracted with EtOAc (200 mL) three times. The organic layer was dried over Na2SO4 andconcentrated to give 5-hydroxy-2-methoxyisonicotinaldehyde (4.2 g, 55%) as a yellow solid. 1H NMR (400 MHz; DMSO) δ= l0.31(s, 1 H), 8.03 (s, 1 H), 6.89 (s, 1 H), 3.80 (s, 3 H). | |
With hydrogenchloride; In tetrahydrofuran; at 50℃; for 1h; | [02601 To a solution of 2-methoxy-5-(methoxymethoxy)isonicotinaldehyde (33.5 g, 0.17 mol,1 eq.) in THF (150 mL) was added HC1 (3 N, 250 mL, 4.4 eq.). The reaction was stirred at 50 Cfor 1 h, cooled to rt, and diluted with water (500 mL). The mixture was neutralized to pH 7-8with solid K2C03. The pale yellow solid was collected, washed with water, and dried to give 5-hydroxy-2-methoxyisonicotinaldehyde (17.9 g, 74.6%) as a pale yellow solid. 1H NMR (400 MHz; DMSO) = 10.31 (s, 1 H), 8.03 (s, 1 H), 6.89 (s, 1 H), 3.80 (s, 3 H). LRMS (M+H+) m/z 154.0. |
17.9 g | With hydrogenchloride; water; In tetrahydrofuran; at 50℃; for 1h; | To a solution of 2-methoxy-5-(methoxymethoxy)isonicotinaldehyde (33.5 g, 0.17 mol) in THF (150 mL) was added HCl (3 N, 250 mL). The reaction was stirred at 50 C. for 1 h, cooled to RT and diluted with water (500 mL). The mixture was neutralized to pH 7-8 with solid K2CO3. The pale yellow solid was collected, washed with water, and dried in vacuum oven (40 C.) overnight to give 5-hydroxy-2-methoxyisonicotinaldehyde (17.9 g, 74.6%). 1H NMR (400 MHz; DMSO)=10.31 (s, 1H), 8.03 (s, 1H), 6.89 (s, 1H), 3.80 (s, 3H); MS (ESI) m/z 154.0 [M+H]+. |
600 mg | With hydrogenchloride; In tetrahydrofuran; at 70℃; for 2h; | To a stirred solution of 2-methoxy-5-methoxymethoxypyridine-4-carbaldehyde (1.5 g, 7.61 mmol) in THF (3 mL) was added 3N HC1 (15 mL) at room temperature and the reaction mixture was heated to 70C for 2 hr. The reaction mixture was cooled under ice bath, neutralizedwith K2C03 and extracted with ethyl acetate (50 mL x 2). The combined organic layer was dried over Na2SO4 and concentrated under reduced pressure to provide the crude product which was purified by column chromatography to afford 600 mg of 5-hydroxy-2-methoxy-pyridine-4- carbaldehyde. ‘H-NMR (DMSO-d6, 400 MHz): ö 10.33 (s, 1H), 10.30 (s, 1H), 8.02 (s, 1H), 6.88 (s, 1H), 3.79 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | 2,5-Dimethoxyisonicotinaldehyde (52). A mixture of 51 (1.28 g, 8.36 mmol) and potassium carbonate(1.73 g, 12.5 mmol) in DMF (50 mL, anhydrous) was heated at 50 C for 10 min. Methyl iodide(1.42 g, 10.0 mmol) was then added and the mixture stirred at this temperature for 2 h. The resultantsolution was diluted with EtOAc and washed with brine three times. The organic layer was dried and evaporated to aord the product 52 (1.39 g, 99%) [23]. 1H NMR (CDCl3) 10.43 (s, 1H), 8.01 (s, 1H),7.08 (d, J = 0.6 Hz, 1H), 3.97 (s, 3H), 3.91 (s, 3H). LRMS: calculated for C8H9NO3: 167.1; found: [M + H]= 168.2. | |
82% | A mixture of <strong>[867267-28-5]5-hydroxy-2-methoxyisonicotinaldehyde</strong> (S31) (2.50 g, 16.33 mmol) and potassium carbonate (3.39 g, 24.45 mmol) in DMF (80 mL, anhydrous) was heated at 50 C for 10 min. Methyl iodide (1.22 ml, 19.59 mmol) was then added and the mixture stirred at this temperature for 2 h. The resultant solution was diluted with EtOAc and washed with brine three times. The organic layer was dried and evaporated to afford 2,5-dimethoxyisonicotinaldehyde (S32). Yield = 2.25 g, 82%. 1H NMR (CDCl3) d 10.4 (s, 1H), 8.01 (s, 1H), 7.07 (s, 1H), 3.97 (s, 3H), 3.91 (s, 3H). Found [M+MeOH]= 200.4 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38% | With potassium carbonate; In N,N-dimethyl-formamide; at 125℃; for 0.25h;Microwave irradiation; | [0173] A mixture of <strong>[867267-28-5]5-hydroxy-2-methoxyisonicotinaldehyde</strong> (723.6 mg, 4.7 mmol), 8- (chloromethyl)-imidazol{1,2-a] pyridine (785 mg, 4.7 mmol), and K2C03 (1.9 g, 14.1 mmol) in DMF (20 mL) was heated at microwave reactor at 125 C for 15 mm. The mixture was filteredand concentrated. The residue was purified on silica gel (50-100% EtOAc in hexanes) to give 5- (imidazo[l,2-a]pyridin-8-ylmethoxy)-2-methoxyisonicotinaldehyde (500 mg, 38%) as an off- white solid. 1H NMR (400 MHz; DMSO) = 10.37 (s, 1 H), 8.58 (d, 1 H), 8.39 (s, 1 H), 8.02 (s, 1 H), 7.61 (s, 1 H), 7.44 (d, 1 H), 6.98 (s, 1 H), 6.93 (t, 1 H), 5.61 (s, 2 H), 3.84 (s, 3 H). LRMS (M+H+) m/z 284.0. |
38% | With potassium carbonate; In N,N-dimethyl-formamide; at 125℃; for 0.25h; | Step 4 ;A mixture of <strong>[867267-28-5]5-hydroxy-2-methoxyisonicotinaldehyde</strong> (723.6 mg, 4.7 mmol), 8-(chloromethyl)-imidazol[1,2-a]pyridine (785 mg, 4.7 mmol), and K2CO3 (1.9 g, 14.1 mmol) in DMF (20 mL) was heated at microwave reactor at 125 C. for 15 min. The mixture was filtered and concentrated. The residue was purified on silica gel (50-100% EtOAc in hexanes) to give 5-(imidazo[1,2-a]pyridin-8-ylmethoxy)-2-methoxyisonicotinaldehyde (500 mg, 38%) as an off-white solid. 1H NMR (400 MHz; DMSO) 6=10.37 (s, 1H), 8.58 (d, 1H), 8.39 (s, 1H), 8.02 (s, 1H), 7.61 (s, 1H), 7.44 (d, 1H), 6.98 (s, 1H), 6.93 (t, 1H), 5.61 (s, 2H), 3.84 (s, 3H). LRMS (M+H+) m/z 284.0. |
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