Structure of 63435-16-5
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CAS No. : | 63435-16-5 |
Formula : | C8H9NO3 |
M.W : | 167.16 |
SMILES Code : | O=C(OC)C1=CC=C(N)C(O)=C1 |
MDL No. : | MFCD00017093 |
InChI Key : | OCZXDVNSNDITBS-UHFFFAOYSA-N |
Pubchem ID : | 7020619 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 44.15 |
TPSA ? Topological Polar Surface Area: Calculated from |
72.55 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.34 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.83 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.77 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.74 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.5 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.83 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.64 |
Solubility | 3.85 mg/ml ; 0.0231 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.94 |
Solubility | 1.94 mg/ml ; 0.0116 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.53 |
Solubility | 4.91 mg/ml ; 0.0294 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 |
No |
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 |
-6.73 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 |
2.0 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) |
1.29 |
* 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 |
---|---|---|
90% | With caesium carbonate; In acetone; for 10h;Heating / reflux; | 4-Amino-3-isopropoxy-benzoic acid methyl ester (3-4). To a solution of 2.045 g (12.23 mmol) methyl 4-amino-3-hydroxybenzoate (3-3) in 40 ml acetone, 1.83 ml 2-iodopropane (18.34 mmol, 1.5 eq.) and 7.97g (24.45 mmol, 2.0 eq.) Cs2CO3 were added. The resulting mixture was refluxed for 10 h and 10 ml of concentrated ammonium hydroxide was added. The solution was refluxed for 30 min and then cooled to room temperature. The mixture was diluted with water and extracted with Et2O. The organic layers were combined and washed with brine then dried with MgSO4. The crude mixture was purified by column chromatography on silica gel (hexane/EtOAc=4/1) to yield 3-4 as a colorless oil (2.300g, 90%). 1H-NMR (400 MHz, CDCl3): delta=1.31 (d, 6H, J=6.07 Hz, 2CH3), 3.82 (s, 3H, CH3), 4.32 (s, 2H, NH2), 4.57 (m, 1H, CH), 6.62 (d, 1H, J=8.17 Hz), 7.44 (d, 1H, J=1.71 Hz), 7.50 (dd, 1H, J1=8.21 Hz, J2=1.80 Hz). 13C-NMR (100 MHz, CDCl3): delta=21.87, 51.43, 70.47, 113.10, 113.68, 118.81, 123.70, 142.22, 143.81, 167.23. HRMS (ESI) m/z: calcd. for C11H16NO3 210.1101, found 210.2032 (M++H). |
60% | With caesium carbonate; In acetone; at 120℃; for 1h;Microwave; | Methyl3-hydroxy-4-aminobenzoate (ABCR: 100 mg, 0.60 mmol) & caesium carbonate (396 mg, 1.22 mmol) were taken up in acetone (4 mL) and 2-iodopropane (90 mul, 0.90 mmol) added and reaction heated in microwave (CEM discover; 150 W) to 120 C. and held for 30 mins A further aliquot of 2-iodopropane (90 mul, 0.90 mmol) was added and reaction heated again to 120 C. in microwave, holding for a further 30 minsThe reaction was repeated twice on a 0.89 mmol scaleReaction mixtures were combined and evaporated to dryness and the residue partitioned between, ethyl acetate (40 ml) and water (50 ml). The organic phase was separated and the aqueous re-extracted with ethyl acetate (40 ml). Combined organic extracts were washed with brine, dried over magnesium sulphate and evaporated to give a brown oil which was purified by column chromatography, on silica (40 g cartridge; ISCO companion) eluting with a rising gradient of 5-50% ethyl acetate in iso-hexane. Product containing fractions were combined and evaporated to dryness to afford the product as a yellow oil (301 mg, 60%)1H NMR (400.132 MHz, DMSO-D6) delta 1.28 (d, 6H), 3.75 (s, 3H), 4.53 (m, 1H), 5.51 (s, 2H), 6.66 (d, 1H), 7.31 (m, 1H), 7.37 (m, 1H); MS m/z 209.4 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | Example 13a; 4-Acetamido-7V-(2-amino-5-(thiophen-2-yl)phenyl)-3-hydroxybenzamide (140; )Step 1 : Methyl 2-methylbenzo[dloxazole-6-carboxylate (138); [0740] A solution of hydroxylamine 137 (0.805 g, 4.815 mmol) was dissolved in trimethyl orthoacetate (MeC(OMe)3) (10 mL, 78.55 mmol) was treated with TFA (0.6 mL, 7.8 mmol) then stirred at room temperature for 90 min. The reaction mixture was diluted with DCM, washed with saturated NaHCO3, brine, dried over MgSO4 and concentrated to give compound 138 (0.911 g, 99% yield).[0741] 1H NMR (DMSO-d6) δ (ppm): 8.19 (s, J= 0.98 Hz, IH), 7.95 (dd, J= 8.4, 1.6 Hz, IH),7.76 (d, J= 8.2 Hz, IH), 3.88 (s, 3H), 2.67 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | at 100℃; for 3.0h; | Example 59; 2-(2, 6-Dichloro-phenylimino)-5- (2-methyl-benzooxazol-6-yl-methylene)-thiazolidin-4-one; a) 2-Methvl-benzooxazole-6-carboxvlic acid methyl ester; A suspension of methyl 4-amino-3-hydroxy-benzoate (30 g, 0.18 mol) in triethylorthoacetate (90 mL) was heated to 100 oC for 3 hours. Ethanol (150 mL) was added followed by water (50 mL). The reaction mixture was filtered to yield 25 g (72 % yield) of pure 2-methyl-benzooxazole-6-carboxylic acid methyl ester. 1H-NMR (CDC13) : 5 2. 67 (s, 3H), 3.94 (s, 3H), 7.65 (d, 1H, J=8.1 Hz), 8.02 (dd, 1H, J=8.1 Hz, J'=1.5 Hz), 8.15 (d, 1H, J=1.5 Hz). LC MS (m/e) = 192.2 (MH+). Rt = 1.70 min |
72% | at 100℃; for 3.0h; | A suspension of methyl 4-amino-3-hydroxy-benzoate (30 g, 0.18 mol) in triethylorthoacetate (90 ml.) was heated to 100 0C for 3 hours. Ethanol (150 ml.) was added followed by water (50 ml_). The reaction mixture was filtered to yield 25 g (72 % yield) of pure 2-methyl-benzooxazole-6-carboxylic acid methyl ester. 1H- NMR (CDCI3): D2.67 (s, 3H), 3.94 (s, 3H), 7.65 (d, 1 H, J=8.1 Hz), 8.02 (dd, 1 H, J=8.1 Hz, J'=1.5 Hz), 8.15 (d, 1 H, J=1.5 Hz). LC MS (m/e) = 192.2 (MH+). Rt = 1.70 min |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80.4% | With pyridinium p-toluenesulfonate; triethylamine; In xylene; for 8.5h;Heating / reflux; | Preparation Example K-1. 2-Methyl-benzoxazole-6-carboxylic acid methyl ester To a solution of 4-amino-3-hydroxy-benzoic acid methyl ester (2085mg, 12.47mmmol) in xylene (200mL) were added acetyl chloride (1.06mL, 14.96mmol), pyridinium p-toluenesulfonate (940mg, 3.74mmol) and triethylamine (2.09mL, 14.96mmol), and the solution was stirred for 8.5 hours under reflux. Ethyl acetate was added to the reaction mixture, which was then washed with water, dried over anhydrous magnesium sulfate, then, evaporated in vacuo, the resulting residue was purified by silica gel chromatography (hexane-ethyl acetate), and the title compound (1917mg, 10.02mmol, 80.4%) was obtained. 1H-NMR Spectrum (CDCl3) δ (ppm): 2.69 (3H, s), 3.96 (3H, s), 7.68 (1H, d, J=8.4Hz), 8.05 (1 H, dd, J=1.2, 8.4Hz), 8.17 (1 H, d, J= 1.2Hz). |
80.4% | With pyridinium p-toluenesulfonate; triethylamine; In xylene; for 8.5h;Heating / reflux; | To a solution of 4-amino-3-hydroxy-benzoic acid methyl ester (2085mg, 12.47mmmol) in xylene (200mL) were added acetyl chloride (1.06mL, 14.96mmol), pyridinium p-toluenesulfonate (940mg, 3.74mmol) and triethylamine (2.09mL, 14.96mmol), and the solution was stirred for 8.5 hours under reflux. Ethyl acetate was added to the reaction mixture, which was then washed with water, dried over anhydrous magnesium sulfate, then, evaporated in vacuo, the resulting residue was purified by silica gel chromatography (hexane-ethyl acetate), and the title compound (1917mg, 10.02mmol, 80.4%) was obtained. 1H-NMR Spectrum (CDCl3) δ(ppm): 2.69 (3H, s), 3.96 (3H, s), 7.68 (1H, d, J=8.4Hz), 8.05 (1 H, dd, J=1.2; 8.4Hz), 8.17 (1 H, d, J= 1.2Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | In methanol; at 20℃; | To methyl 4-amino-3-hydroxybenzoate (7a) (10.8 g, 0.065 mol) in MeOH (125 mL) was added dimethyl acetimidate hydrochloride (9.2 g, 0.084 mol), and the mixture was stirred overnight at room temperature with MeOH (30 mL) added to maintain fluidity. The solids (6.7 g) were collected by filtration, and the ML was concentrated. The residue was triturated with EtOAc affording additional solids (5.5 g). The tan solids were combined (12.2 g, 99% yield): mp 103-104 C (lit.39 103-104 C); TLC (SiO2, ethyl acetate/chloroform, methanol, concentrated ammonium hydroxide (90:8:1.8:0.2), UV) single spot Rf 0.76; MS MH+ 192.2. 1H NMR (300 MHz, CDCl3); δ 2.69 (s, 3H, NCH3), 3.96 (s, 3H, OCH3), 7.68 (d, J = 8.3 Hz, 1H, H-5), 8.05 (dd, J = 8.3, 1.5 Hz, 1H, H-4), 8.17 (d, J = 1 Hz, 1H, H-7). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82.7% | This compound was prepared with minor modifications as described in PCT int. Appl. 2005079541 (01 Sept. 2005) as follows: To a solution of Methyl 4-amino-3 -hydro ybenzoate (l .Og, 6.0 mmol) in acetone (20 mL) at ambient temperature was added 2-bromopropane (l .lg, 9.0 mmol) followed by cesium carbonate (3.9g, 12 mmol) each in one portion. The resulting mixture was heated a reflux temperature for 6 hr. Concentrated ammonium hydroxide (5 mL) was added and the mixture was refluxed for an additional 30 min. After cooling to ambient temperature the mixture was diluted with water (100 mL) and extracted with 3X 75 mL of diethyl ether. The combined extracts were washed with 2X 50 mL of brine and dried over magnesium sulfate. The mixture was filtered and concentrated in vacuo. The residue was taken up in diethyl ether, silica gel was added and the mixture concentrated in vacuo. The residue was transferred to a pre- column and purified by chromatography using initially hexanes (1 min.) as eluent. The eluent was modified to 30% ethyl acetate/hexanes over a 15 min. period and kept at 30% ethyl acetate/hexanes for the remainder of the purification. Fractions containing the pure desired component were combined and concentrated in vacuo to give 1.03g (82.7% yield) of a pale yellow oil that solidified on standing to a white solid. MS: m/z 210.1 (MKT). 1H NMR (500 MHz, DMSO-d6): delta 1.279 (d, 6H), 3.744 (s, 3H), 4.525 (m, 1H), 5.532 (s; 2H), 6.651 (d, 1H), 7.299 (d,lH), 7.363 (dd, 1H). |
Tags: 63435-16-5 synthesis path| 63435-16-5 SDS| 63435-16-5 COA| 63435-16-5 purity| 63435-16-5 application| 63435-16-5 NMR| 63435-16-5 COA| 63435-16-5 structure
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H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
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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