Structure of 614-18-6
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CAS No. : | 614-18-6 |
Formula : | C8H9NO2 |
M.W : | 151.16 |
SMILES Code : | O=C(OCC)C1=CN=CC=C1 |
MDL No. : | MFCD00006389 |
InChI Key : | XBLVHTDFJBKJLG-UHFFFAOYSA-N |
Pubchem ID : | 69188 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 40.32 |
TPSA ? Topological Polar Surface Area: Calculated from |
39.19 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.87 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.32 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.26 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.66 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.51 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.32 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.81 |
Solubility | 2.32 mg/ml ; 0.0153 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.74 |
Solubility | 2.73 mg/ml ; 0.018 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.49 |
Solubility | 0.491 mg/ml ; 0.00325 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.28 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.36 |
* 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 |
---|---|---|
52% | With sodium ethanolate; for 16h;Heating / reflux; | (1). Sodium (38 g, 1.65 mol) was slowly added to 900 mL of ethanol and left to stir at RT for 4 h. Solvent was removed in vacuo. Ethyl acetate (200 mL) was addded to the sodium ethoxide followed by ethyl nicotinate (22.6 mL, 0.166 mol) in 150 mL of ethyl acetate. The reaction was heated to reflux for 16 h. Water (200 mL) was added to the reaction mixture. The aqueous layer was acidified to pH 6 with HCl and extracted with ether. Solvent was removed in vacuo to give a brown oil which was purified by column chromatography (2:1, hexanes-EtOAc), to give 1 (101 g, 52%). |
37.1% | With lithium tert-butoxide; for 4h;Reflux; | Add 10 ml of ethyl acetate to a 25 ml round bottom flask.Ethyl nicotinate 1.0g,Lithium tert-butoxide 0.794g,The reaction was refluxed for 4 hours, and the reaction was completed by TLC. The reaction mixture was cooled to room temperature, and 60 ml of 3M HCl solution was added thereto and stirred for 5 minutes. Then, the organic layer was separated and the aqueous layer was extracted with ethyl acetate (90 ml). Dry over sodium sulfate, filter, concentrate,The compound 3-oxo-(3-pyridyl)propionic acid ethyl ester is obtained.The colorless oil was 0.474 g, and the yield was 37.1%. |
3 g | With sodium ethanolate; for 20h;Reflux; | Ethyl 3-picolinate (2.5 g, 16 mmol) was weighed out in a 250 mL eggplant flask,Followed by 60 mL of EA,NaOEt 12 g (176 mmol),Heated to reflux after 20h to stop the reaction,Was removed by rotary evaporation EA, with 2mol / L HCl adjusted to pH 8-9, 3 times (3 × 40mL), the combined organic phase was extracted with EA, dried over anhydrous Na2SO4, separation and purification by column chromatography (petroleum ether / ethyl acetate = 3/ 1) to give 3 g of a yellow oily liquid which was used directly in the next step. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96.6% | (A) A mixture of 1.6 kg of ethyl nicotinate,Ethanolamine 1.1kg into the reactor.The reaction was heated to 125 C for 4 hours.After completion of the reaction,Cooled to 100 C,Vacuum distillation,Vacuum distillation vacuum-0.091MPa distillation temperature rose to 130 ~ 135 when the end of distillation, the reaction solution;(B) The reaction solution can be rapidly cooled to 80 C with brine under stirring,And then slowly cooled to 65 ;(C) 1.6 kg of acetone was added dropwise at 60 C,After the dropwise addition was continued, the temperature was gradually lowered to 45 C,Crystal precipitation,And the mixture was stirred at 45 C for 1 hour.(D) continue to cool to 30 C,Stir for 1.5 hours,And then continue to cool to 10-15 ,Stirred for 1 hour,And then continue to cool to 0 or so,Stirring crystallization after 1 hour out.Centrifugation,The filter cake,The oven was dried at 50-60 & lt; 0 & gt; C,To obtain 1.70 kg of white N- (2-hydroxyethyl) -nicotinamide,The overall yield was 96.6%Mp 89-91 C. | |
64.5% | EXAMPLE 91 Preparation of N-(2-Hydroxyethyl)-3-pyridinecarboxamide A neat mixture of 2-aminoethanol (6.1 g, 0.10 mol) and ethyl nicotinate (15.1 g, 0.10 mol) was refluxed overnight. As the mixture was cooled to room temperature, the product precipitated as a crystalline solid. It was filtered, washed with ether and then recrystallized from 2-propanol/ether. The final productproduct was collected by vacuum filtration and washed with ether. The dried, white compound weighed 10.7 g, resulting in a 64.5% yield; mp 88.5-89.5 C. (lit. value 92 C.). | |
64.5% | EXAMPLE 91 Preparation of N-(2-Hydroxyethyl)-3-pyridinecarboxamide A neat mixture of 2-aminoethanol (6.1 g, 0.10 mol) and ethyl nicotinate (15.1 g, 0.10 mol) was refluxed overnight. As the mixture was cooled to room temperature, the product precipitated as a crystalline solid. It was filtered, washed with ether and then recrystallized from 2-propanol/ether. The final productproduct was collected by vacuum filtration and washed with ether. The dried, white compound weighed 10.7 g, resulting in a 64.5% yield; mp 88.5-89.5 C. (lit. value 92 C). |
64% | at 20 - 55℃; for 18h; | General procedure: For the synthesis of the hydroxylated precursors, ethanolamine (1.5 mmol) was added slowly to the esters (1 mmol) at 55C and stirred for 3 h. The reaction mixture was stirred at room temperature for 15 h. The residue was purified by silica gel column chromatography (eluent/ethyl acetate/hexane 8:2) or recrystallized from ethyl acetate. The progress of the reaction was monitored by TLC.` |
42% | In toluene; at 80℃; for 48h; | Ethyl nicotinate (15.1 g, 100.0 mmol, 1.0 eq.) and Ethanolamine (6.1 g, 100.0 rnrnol, 1.0 eq.) were dissolved in toluene (80 ml_). The reaction mixture was heated to 80 0C and stirred for 48 h. During the reaction the mixture changed into a sticky emulsion. The emulsion was cooled down to room temperature and the lower phase became solid. The upper liquid phase was decanted and the orange solid was crystallised twice, first from ethyl acetate and then from acetone. The crystals were dried under high vacuum at room temperature to give 7.1 g (42 %) of the product as a white, free flowing powder. The 1 H NMR and the 13C NMR corresponds to the literature (Ogawa, T.; Hatayama, K.; Maeda, H.; Kita, Y. Chem. Pharm. Bull. 1994, 42 (8) 1579-1589). 1H NMR (CDCI3) delta = 3.60-3.64 (q, 2H), 3.82-3.85 (t, 2H), 4.00 (s, 1H), 7.33-7.39 (m, 2H), 8.10-8.14 (m, 1H), 8.64-8.67 (q, 1 H)1 8.99-9.00 (t, 1 H). 13C NMR (CDCI3) delta = 42.8, 61.5, 123.6, 130.2, 135.5, 147.8, 152.0, 166.4. |
EXAMPLE 58 Preparation of N-(2-Hydroxyethyl)-3-pyridinecarboxamide A solution of 49.2 g (0.32525 mol) ethyl nicotinate and 72 g (1.17 mol) ethanolamine was heated at 70 C. for 60 hours. The excess ethanolamine was removed under reduced pressure and the resulting viscous cream oil was stirred with ether for 48 hours. The resulting white solid was removed by filtration, affording 46 g (85.1%) of the title compound melting at 75-78 C. | ||
EXAMPLE 58 Preparation of N-(2-Hydroxyethyl)-3-pyridinecarboxamide A solution of 49.2 g (0.32525 mol) ethyl nicotinate and 72 g (1.17 mol) ethanolamine was heated at 70 C. for 60 hours. The excess ethanolamine was removed under reduced pressure and the resulting viscous cream oil was stirred with ether for 48 hours The resulting white solid was removed by filtration, affording 46 g 15 (85 1%) of the title compound melting at 75-78 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure D for the Synthesis of Fluoroethyl Aryl Pyridinyl Substituted Ethyl Ureas: An (iso)nicotinic acid ethyl ester and a substituted phenyl acetonitrile (1:1 ratio) were dissolved in EtOH (100 mL), then sodium ethoxide (21% in EtOH, 1.0 eq was added. The resulting reaction mixture was refluxed for 3 hours, then cooled to 0 C., concentrated HCl was added to adjust the acidity to pH=3. A solid, presumably the intermediate cyanoketone, was formed and filtered. The solid was then washed with water and dried under house vacuum. This cyanoketone was mixed with 48% hydrobromic acid (80 mL) and the mixture was refluxed for 5 hours. After cooling to room temperature, the reaction mixture was basified with ammonium hydroxide, and then extracted with ethyl acetate. The combined organic phases were washed with brine, then dried with magnesium sulfate and concentrated to give the desired diaryl ketone42. This ketone was then converted into the desired amine via oxime intermediate according to the protocol described in general procedure B. The final fluoroethyl urea was thus obtained using this amine and fluoroethyl ammonium chloride according to general procedure A. 42 Clader, John W.; Berger, Joel G.; Burrier, Robert E.; Davis, Harry R.; Domalski, Martin; et al. J. Med. Chem. 1995, 38, 1600-1607. The title ketone was obtained from nicotinic acid ethyl ester (10.00 g, 66.16 mmol), (2-fluoro-phenyl)-acetonitrile (9.12 g, 67.49 mmol), sodium ethoxide (50.00 mL, 21 wt. % in EtOH, 0.13 mol) and hydrobromic acid (48%, 80.00 mL) according to the protocols as outlined in general procedure D described above. Spectroscopic data: 1H NMR (300 MHz, DMSO-d6) delta ppm 4.53 (s, 2H) 7.10-7.23 (m, 2H) 7.24-7.36 (m, 2H) 7.58 (dd, J=7.92, 5.57 Hz, 1H) 8.36 (dt, J=8.14, 1.94 Hz, 1H) 8.81 (dd, J=4.84, 1.61 Hz, 1H) 9.22 (d, J=1.47 Hz, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
p-xylyl-(3-pyridyl)-ketone, m.p. 90-91C (from ether), starting from 21.0 g of p-tolylacetic acid ethyl ester and 17.8 g of nicotinic acid ethyl ester; m-chlorobenzyl-(3-pyridyl)-ketone, m.p. 65-67C, starting from 25.0 g of m-chlorophenylacetic acid ethyl ester and 19.0 g of nicotinic acid ethyl ester; p-chlorobenzyl-(3-pyridyl)-ketone (oil), starting from 25.0 g of p-chlorophenylacetic acid ethyl ester and 19.0 g of nicotinic acid ethyl ester; p-methoxybenzyl(4-pyridyl)-ketone, m.p. 130-132C, starting from 25.2 g of p-methoxyphenylacetic acid ethyl ester and 18.9 g of nicotinic acid ethyl ester; m-methoxybenzyl-(3-pyridyl)-ketone, b.p. 160-165C/0.05 Torr, starting from 25.2 g of m-methoxyphenylacetic acid ethyl ester and 19.0 g of nicotinic acid ethyl ester. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With lithium hexamethyldisilazane; In tetrahydrofuran; at -40℃; for 0.333333h;Inert atmosphere; | General procedure: To the solution of ester (10 mmol) in THF (20 mL) and ethyl acetate (70 mmol), LiHMDS (30 mmol) was added very quickly at -40 C, and stirred at this temperature for 20 min. After completion of the reaction, reaction mixture was quenched with acetic acid (50 mmol) and then basified using 10% NaHCO3 solution, extracted with ethyl acetate (2×100 mL), the combined organic layer was washed with water and brine solution and dried over Na2SO4. The specific purification procedure for each compound has been included along with their characterization data. |
Tags: 614-18-6 synthesis path| 614-18-6 SDS| 614-18-6 COA| 614-18-6 purity| 614-18-6 application| 614-18-6 NMR| 614-18-6 COA| 614-18-6 structure
A328129 [273203-62-6]
Tetradecyl pyridine-3-carboxylate
Similarity: 0.96
A328129 [273203-62-6]
Tetradecyl pyridine-3-carboxylate
Similarity: 0.96
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H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
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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