Structure of 98400-69-2
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CAS No. : | 98400-69-2 |
Formula : | C10H14N2O2 |
M.W : | 194.23 |
SMILES Code : | C(C)(C)(C)OC(=O)NC1=CC=NC=C1 |
MDL No. : | MFCD02179232 |
InChI Key : | DRZYCRFOGWMEES-UHFFFAOYSA-N |
Pubchem ID : | 9990210 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H317 |
Precautionary Statements: | P280 |
* 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 |
---|---|---|
35% | Stage #1: With n-butyllithium In tetrahydrofuran at -78 - 0℃; for 0.5 h; Inert atmosphere Stage #2: at -78 - 20℃; for 2 h; |
To a stirred solution of BL (12 g, 0.06 mol) in dry THF (200 mL) under inert atmosphere was added n-butyl lithium (79.12 mL, 0.18 mol) at -78 °C. The reaction was warmed to 0 °C and stirred for 30 min. Carbon dioxide gas was added to the reaction mass at -78 °C for 1 h, then at RT for 1 h. The reaction was monitored by TLC. After complete consumption of the starting material, the reaction mass was diluted with water (200 mL) and washed with diethyl ether (2x150 mL). The aqueous layer was acidified with citric acid to pH~4. The obtained solid was filtered and dried under vacuum to afford BM (5.1 g, 35percent) as a white solid. *H NMR (400 MHz, DMSO-i: δ 11.76 (br s, 1H), 8.96 (s, 1H), 8.52 (d, / = 15.0 Hz, 1H), 8.22 (d, / = 15.0 Hz, 1H), 1.49 (s, 9H). |
30% | Stage #1: With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran at -40 - 20℃; for 0.333333 h; Stage #2: at -78 - 20℃; for 3.25 h; |
-Buli (1.6 M soln, 155 mL, 249 mmol) was added to a stirred solution of TMEDA (37.36 mL, 249 mmol) in THF AT-40 °C. The solution was allowed to come at room temperature over 10 min and stirred for another 10 min. The solution was cooled TO-78 °C. A solution OF PYRIDINE-4-YL-CARBAMIC acid-tert-butyl ester (117) (22 g, 113.26 mmol) in THF was added slowly. The solution was allowed to come at room temperature within 3 h. After stirring at room temperature for 15 min the solution was again cooled to -78 OC and a freshly crushed dry ice was added. The solution was allowed to come at room temperature, stirred for 30 min and poured into ice cold 10 percent NH4C1 solution. The solution was basified by IN NaOH solution and washed by dichloromethane. The pH of aqueous phase was adjusted to 4 by cold 10 percent HC1 solution. The solids formed were filtered, washed by water and dried under vacuum at room temperature to yield 16.3 g (30 percent) 4-tert-butoxycarbonylamino-nicotinic acid (118) as white solids. MP: 260 °C ; 1H- NMR (DMSO-d6): d 1.49 (s, 9H), 8.23 (d, J= 6.0 Hz, 1H), 8.55 (D, J= 6.0 Hz, 1H), 8. 96 (s, 1H); EIMS M/Z 238 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With carbon dioxide In tetrahydrofuran; pentane | B. 4-(Boc-amino)pyridine-3-carboxylic Acid. To a stirring solution of 4-(Boc-amino)pyridine (1.027 g, 5.30 mmol) in THF at -36 °C (internal temperature) was added a 1.7 M solution of t-butyl lithium in pentane(6.5 mL, 11 mmol), and the rate of addition was controlled so as to keep the internal temperature below -28 °C. After an additional hour (temperature kept between -30 °C and -50 °C) carbon dioxide (g) was bubbled through the solution and the cold bath was removed. After about 15 min, the mixture was poured into ice water and the aqueous phase was washed with dichloromethane. The pH was adjusted to 4-5 with citric acid and the resulting precipitate was washed with dichloromethane and methanol and dried in vacuo to give 0.811 g (64percent) of an off-white solid. 1H-NMR IS-MS, m/e 239.0 (m+1) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | To a stirred solution of BL (12 g, 0.06 mol) in dry THF (200 mL) under inert atmosphere was added n-butyl lithium (79.12 mL, 0.18 mol) at -78 C. The reaction was warmed to 0 C and stirred for 30 min. Carbon dioxide gas was added to the reaction mass at -78 C for 1 h, then at RT for 1 h. The reaction was monitored by TLC. After complete consumption of the starting material, the reaction mass was diluted with water (200 mL) and washed with diethyl ether (2x150 mL). The aqueous layer was acidified with citric acid to pH~4. The obtained solid was filtered and dried under vacuum to afford BM (5.1 g, 35%) as a white solid. *H NMR (400 MHz, DMSO-i: delta 11.76 (br s, 1H), 8.96 (s, 1H), 8.52 (d, / = 15.0 Hz, 1H), 8.22 (d, / = 15.0 Hz, 1H), 1.49 (s, 9H). | |
30% | -Buli (1.6 M soln, 155 mL, 249 mmol) was added to a stirred solution of TMEDA (37.36 mL, 249 mmol) in THF AT-40 C. The solution was allowed to come at room temperature over 10 min and stirred for another 10 min. The solution was cooled TO-78 C. A solution OF PYRIDINE-4-YL-CARBAMIC acid-tert-butyl ester (117) (22 g, 113.26 mmol) in THF was added slowly. The solution was allowed to come at room temperature within 3 h. After stirring at room temperature for 15 min the solution was again cooled to -78 OC and a freshly crushed dry ice was added. The solution was allowed to come at room temperature, stirred for 30 min and poured into ice cold 10 % NH4C1 solution. The solution was basified by IN NaOH solution and washed by dichloromethane. The pH of aqueous phase was adjusted to 4 by cold 10 % HC1 solution. The solids formed were filtered, washed by water and dried under vacuum at room temperature to yield 16.3 g (30 %) 4-tert-butoxycarbonylamino-nicotinic acid (118) as white solids. MP: 260 C ; 1H- NMR (DMSO-d6): d 1.49 (s, 9H), 8.23 (d, J= 6.0 Hz, 1H), 8.55 (D, J= 6.0 Hz, 1H), 8. 96 (s, 1H); EIMS M/Z 238 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | tert-Butyl (3-bromopyridin-4-yl)carbamate (3f) (52%) was prepared from pyridine 2f (2.70 g, 13.9 mmol) [34]. White solid; mp 91-92 C. 1H NMR (400 MHz, CDCl3) delta 8.58 (s, 1H), 8.37 (d, J=5.6 Hz, 1H), 8.15 (d, J=5.6 Hz, 1H), 7.18 (s, 1H), 1.55 (s, 9H); 13C NMR (101 MHz, CDCl3) delta 151.6, 151.4, 149.4, 143.1, 113.1, 109.6, 82.4, 28.1 (3C). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54 - 58% | n-Butyllithium (1.6 M in hexanes; 220 ml, 0.35 mol) was slowly dropwise over 30 min to a stirred solution of pyridin-4-yl-carbamic acid tert-butyl ester (26.08 g, 0.13 mol) and N,N,N,N-tetramethylethylenediamine (55 ml, 0.36 mol) in tetrahydrofuran (750 ml) at -78 C. The solution was stirred at-78 C for 15 min and 2 h at-10 C. The mixture was cooled to -78 C and a solution of iodine (95.11 g, 0.37 mol) in tetrahydrofuran (250 ml) was added dropwise over 30 min. The mixture was stirred for a further 2 h and then the mixture was quenched with water (250 ml) at 0 C. A saturated solution of sodium sulfite (100 ml) was added and the organic layer separated. The aqueous layer was extracted with dichloromethane (2 x 500 ml) and then the combined organic extracts were dried and concentrated in vacuo to give a brown oil. Purification by flash column chromatography on silica gel eluting with 20 % ethyl acetate : heptane gave (3-iodo-pyridin-4-yl)-carbamic acid tert-butyl ester (25.00 g, 58 %) as an off-white solid, No.H (400 MHz, CDC13) 8.76 (1H, s), 8.35 (1H, d J 5.7 Hz), 8.11 (1H, d J 5.7 Hz), 7.04 (lH, br s), 1.55 (9H, s) ; Tr = 0.99 min, m/z (ES+) (M+H)+ 321.08. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | In tetrahydrofuran; water; | 4-(N-t-Butoxycarbonylamino)nicotinic acid. n-Butyl lithium (2.18M, 24 mL, 52.51 mmol) is added slowly to a solution of 4-(N-t-butoxycarbonylamino)pyridine (4.08 g, 21 mmol) in THF (50 mL, stirred under N2 at -78 C. The solution is allowed to warm to 0 C., stirred for 3 h, then cooled again to -78 C. and poured into ether (100 mL) containing dry ice. The solution is warmed to room temperature with constant stirring. Water is added and the mixture is neutralized with acetic acid. The resulting solid is collected by vacuum filtration and dried in a vacuum oven to give 4-(N-t-butoxycarbonylamino)nicotinic acid (2.72 g, 54%) as a brown solid. 1 H NMR (DMSO) delta 11.75 (1H, brs), 8.95 (1H, s), 8.50 (1H, d, J=6.0 Hz), 8.20 (1H, d, J=6.0 Hz), 1.49 (9H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.811 g (64%) | With carbon dioxide; In tetrahydrofuran; pentane; | B. 4-(Boc-amino)pyridine-3-carboxylic Acid. To a stirring solution of 4-(Boc-amino)pyridine (1.027 g, 5.30 mmol) in THF at -36 C (internal temperature) was added a 1.7 M solution of t-butyl lithium in pentane(6.5 mL, 11 mmol), and the rate of addition was controlled so as to keep the internal temperature below -28 C. After an additional hour (temperature kept between -30 C and -50 C) carbon dioxide (g) was bubbled through the solution and the cold bath was removed. After about 15 min, the mixture was poured into ice water and the aqueous phase was washed with dichloromethane. The pH was adjusted to 4-5 with citric acid and the resulting precipitate was washed with dichloromethane and methanol and dried in vacuo to give 0.811 g (64%) of an off-white solid. 1H-NMR IS-MS, m/e 239.0 (m+1) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With n-butyllithium; N,N,N,N,-tetramethylethylenediamine; iodine; In tetrahydrofuran; | Reference Example 49 (3-iodo-pyridin-4-yl)-carbamic acid tert-butyl ester. To a solution of pyridin-4-yl-carbamic acid tert-butyl ester (14.8 g, 76.3 mmol) (reference example 44b) in THF (300 mL) is added N,N,N',N'-tetramethylethylene-diamine (34.5 mL, 230 mmol) and the solution cooled to -78 C. To this solution is added slowly (2.5M) n-butyllithium (91.5 mL, 230 mmol), the reaction temperature allowed to rise to -20 C. and the resulting mixture stirred for 1.5 hours. The mixture is cooled to -78 C. and a solution of iodine (29.04 g, 114 mmol) in THF (60 mL) is added then stirred for 10 min. The mixture is warmed to 20 C., stirred 30 min then diluted with ethyl acetate, washed with water, sat. sodium thiosulfate and brine, dried over MgSO4 and concentrated. The residue is purified by flash chromatography (eluding with 20% ethyl acetate in hexanes) to give 17.7 g of title compound as a light yellow crystalline solid. 1H NMR (CDCl3) delta 1.54 (s, 9H), 7.03 (bs, 1H), 8.10 (d, J=6 Hz, 1H), 8.34 (d, J=6 Hz, 1H), 8.74 (s, 1H). MS (EI) m/z 320 (M+). |
Tags: 98400-69-2 synthesis path| 98400-69-2 SDS| 98400-69-2 COA| 98400-69-2 purity| 98400-69-2 application| 98400-69-2 NMR| 98400-69-2 COA| 98400-69-2 structure
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H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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