Structure of 775545-30-7
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CAS No. : | 775545-30-7 |
Formula : | C7H7NO3 |
M.W : | 153.14 |
SMILES Code : | O=C(O)C1=CN=C(CO)C=C1 |
MDL No. : | MFCD11977430 |
InChI Key : | HJDYJONTIWRYOB-UHFFFAOYSA-N |
Pubchem ID : | 14722130 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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 |
---|---|---|
4C. 6-Hydroxymethyl-nicotinic acid A solution of 6-hydroxymethyl-nicotinic acid methyl ester (0.400 g, 2.38 mmol) in 1.0 N NaOH (25.0 mL) and methanol (10.0 mL) was heated at 80 C. for 1 hour. The reaction mixture was cooled to room temperature and the pH was adjusted to 7.0 with 1.0 N HCl. The reaction mixture was concentrated in vacuo and the resulting salt was slurried in DMF and filtered to provide the title compound. ESI-MS: 154 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In acetonitrile; at 0 - 20℃; for 2h; | 6-Hydroxymethyl-nicotinic acid was synthesized by the method described in (BIOORG. Med. Chem. Lett, 1996, 6, 3025-3028). To a solution of 7-AMINO-1, 2,3-trimethoxy-10- METHYLSULFANYL-6, 7-DIHYDRO-5H-BENZO [A]-HEPTALEN-9-ONE (300 mg, 0.80 mmol), 6-hydroxymethylnicotinic acid (135 mg, 0.88 mmol) and DMAP (60 mg, 0.48 mmol) in 10 mE of acetonitrile was added EDCI (308 mg, 1.60 mmol) at 0C. The reaction mixture was stirred at room temperature for 2 hours. Water was added to quench the reaction, and aqueous layer was extracted with ethyl acetate. Combined organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (ethyl acetate: methanol = 8 : 1), to give 244 mg (yield: 60%, solid having yellow color) of the target compound. 1H NMR (400MHZ, CDC13) : 62. 07-2. 15 (m, 1H), 2. 31- 2.44 (m, 2H), 2.45 (s, 3H), 2.56-2. 59 (m, 1H), 3.75 (s, 3H), 3. 91 (s, 3H), 3. 97 (s, 3H), 4. 66 (q, J=10. 2HZ, 2H), 4. 90- 4.93 (m, 1H), 6.56 (s, 1H), 7.13 (t, J=9. lHz, 2H), 7.40 (d, J=10.2Hz, 1H), 7.52 (s, 1H), 8.15 (dd, J=2. 2,5. 8Hz, 1H), 8.80 (d, J=6.9Hz, 1H), 8.96 (s, 1H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; sodium hydroxide; In methanol; | Reference Example 10 6-Hydroxymethylpyridine-3-carboxylic acid (Reference Compound No.10-1) Under ice cooling, 2 M aqueous sodium hydroxide solution (3.0 mL) was added to a solution of 6-acetoxymethylpyridine-3-carboxylic acid methyl ester (Reference Compound No.9-1, 0.60 g, 2.9 mmol) in methanol (6.0 mL). The reaction mixture was stirred under ice cooling for 40 minutes and at room temperature for 4 hours. Under ice cooling, 2 M hydrochloric acid (3.1 mL) was added thereto, and then the solvent was evaporated under reduced pressure to give the title reference compound as an orange solid. | |
Reference Example 10 6-Hydroxymethylpyridine-3-carboxylic acid (Reference Compound No.10-1) Under ice cooling, 2 M aqueous sodium hydroxide solution (3.0 mL) was added to a solution of 6-acetoxymethylpyridine-3-carboxylic acid methyl ester (Reference Compound No.9-1, 0.60 g, 2.9 mmol) in methanol (6.0 mL). The reaction mixture was stirred under ice cooling for 40 minutes and at room temperature for 4 hours. Under ice cooling, 2 M hydrochloric acid (3.1 mL) was added thereto, and then the solvent was evaporated under reduced pressure to give the title reference compound as an orange solid. 1H-NMR (400 MHz, DMSO-d6) delta 4.64 (s, 2H), 5.31 (br s, 1H), 7.63 (d, J = 8.2 Hz, 1H), 8.30 (dd, J = 8.2, 2.2 Hz, 1H), 8.97 (d, J = 2.2 Hz, 1H), 13.34 (s, 1H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In water; N,N-dimethyl-formamide; | Reference Example 11 N-(2-t-Butoxycarbonylaminophenyl)-<strong>[775545-30-7]6-hydroxymethylpyridine-3-carboxylic acid</strong> amide (Reference Compound No.11-1) 2-Aminophenyl carbamic acid t-butyl ester (Reference Compound No.1-1, 0.60 g, 2.9 mmol), N,N-diisopropylethylamine (1.5 mL, 8.6 mmol), and HATU (1.1 g, 2.9 mmol) were added to a suspension of <strong>[775545-30-7]6-hydroxymethylpyridine-3-carboxylic acid</strong> (Reference Compound No. 10-1) in DMF (10 mL), and then the reaction mixture was stirred at room temperature for 2 hours. Water (200 mL) was added thereto, the whole was extracted with ethyl acetate (100 mL, 50 mL), and then the organic layer was washed with brine (100 mL) twice. After the organic layer was dried over anhydrous magnesium sulfate, the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give 0.66 g of the title reference compound as a brown oil. (Yield 67% in 2 steps) |
With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 20℃; for 2h; | 2-Aminophenyl carbamic acid t-butyl ester (Reference Compound No.1-1, 0.60 g, 2.9 mmol), N,N-diisopropylethylamine (1.5 mL, 8.6 mmol), and HATU (1.1 g, 2.9 mmol) were added to a suspension of <strong>[775545-30-7]6-hydroxymethylpyridine-3-carboxylic acid</strong> (Reference Compound No.10-1) in DMF (10 mL), and then the reaction mixture was stirred at room temperature for 2 hours. Water (200 mL) was added thereto, the whole was extracted with ethyl acetate (100 mL, 50 mL), and then the organic layer was washed with brine (100 mL) twice. After the organic layer was dried over anhydrous magnesium sulfate, the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give 0.66 g of the title reference compound as a brown oil. (Yield 67% in 2 steps) [Show Image] 1H-NMR (400 MHz, DMSO-d6) delta 1.44 (s, 9H), 4.65 (d, J = 5.9 Hz, 2H), 5.59 (t, J = 5.9 Hz, 1H), 7.14 (td, J = 7.7, 1.5 Hz, 1H), 7.21 (td, J = 7.7, 1.5 Hz, 1H), 7.52 (dd, J = 7.7, 1.5 Hz, 1H), 7.59 (dd, J = 7.7, 1.5 Hz, 1H), 7.63 (d, J = 8.3 Hz, 1H), 8.31 (dd, J = 8.3, 2.1 Hz, 1H), 8.69 (s, 1H), 9.03 (d, J = 2.1 Hz, 1H), 9.94 (s, 1H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In dichloromethane; at 20℃; for 0.333333h; | [1- [2- (methylamino) ethyl] -4-piperidinyl] N- (2-phenylphenyl) carbamate (0.35 g, 1 mmol) (9A) (Refer to J. Med. Chem., 2015, 58 (6), prepared by pp 2609-2622) was dissolved in dichloromethane (30 mL), and 6- (hydroxymethyl) pyridine-3-carboxylic acid (9B) ( 0.15g, 1mmol) (prepared from WO2013041535), after stirring, add triethylamine (0.2g, 2mmol) and HATU (0.57g, 1.5mmol) in order, and react at room temperature for 20 minutes. After the reaction was completed, a saturated aqueous sodium hydrogen carbonate solution (30 mL) was added, and the mixture was extracted with dichloromethane (30 mL × 2), washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was subjected to silica gel column chromatography. Separation (dichloromethane / methanol (v / v) = 40: 1) gives [1- [2-[[6- (hydroxymethyl) pyridine-3-carbonyl] -methyl-amino] ethyl] -4 -Piperidinyl] N- (2-phenylphenyl) carbamate (29C), a colorless viscous substance (0.42 g, yield: 87%). |