Structure of 269410-26-6
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CAS No. : | 269410-26-6 |
Formula : | C18H21BO3 |
M.W : | 296.17 |
SMILES Code : | CC1(OB(C2=CC=C(OC3=CC=CC=C3)C=C2)OC1(C)C)C |
MDL No. : | MFCD06795691 |
InChI Key : | SFCRPRMZQXUXOG-UHFFFAOYSA-N |
Pubchem ID : | 17750275 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 22 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.33 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 89.43 |
TPSA ? Topological Polar Surface Area: Calculated from |
27.69 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
4.44 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.78 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.66 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.98 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.77 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.68 |
Solubility | 0.0062 mg/ml ; 0.0000209 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.74 |
Solubility | 0.00539 mg/ml ; 0.0000182 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-6.24 |
Solubility | 0.000169 mg/ml ; 0.00000057 mol/l |
Class? Solubility class: Log S scale |
Poorly 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) |
Yes |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
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) |
Yes |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
Yes |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-4.95 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 |
0.0 |
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 |
1.0 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) |
3.24 |
* 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 |
---|---|---|
[00432] In a reaction tube under nitrogen, a mixture of PdCl2(dppf)CH2Cl2 (22 mg; 0.027 mmol) and triethylamine (0.36 ml; 2.58 mmol) in dioxane (4 ml; dried over 4 ? sieves) was sealed and stirred at 80 C. overnight (18 h). After cooling to room temperature, HB(pin) (0.19 ml;, 1.31 mmol) and 4-bromodiphenyl ether (216 mg; 0.865 mmol) were added and the reaction mixture was stirred at 80 C. GC analysis after 18 h showed a peak at 13.84 mins which was identified by GC/MS as the desired compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In dimethyl sulfoxide; at 20℃; for 0.5h; | General procedure: General procedure: The synthetic procedure for pentafluorophenyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenesulfonate (a) is presented as an example (Scheme 1). 2,2'-Bis(1,3,2-benzodioxaborole) (cat2B2, 262 mg, 1.10 mmol), PdCl2(dppf) (25 mg, 0.030 mmol), AcOK (294 mg, 3.0 mmol), pentafluorophenyl 4-bromobenzenesulfonate (403 mg, 1.0 mmol), and EtOH (6.0 mL) were charged in a reaction vessel under an Ar atmosphere. The resulting mixture was stirred for 2 h at 80 C. After cooling to room temperature, pinacol (260 mg, 2.20 mmol) was added to the mixture. The mixture was further stirred for 30 min at room temperature. H2O and n-hexane were added to the mixture and the product was extracted into the organic layer. After drying the organic layer with anhydrous MgSO4, solids were removed by filtration. The filtrate was concentrated. The product was obtained as a white solid by Kugelrohr distillation. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 60 - 90℃; | b) tert-butyl 6-(4-amino-3-(4-phenoxyphenyl)-lH-pyrazolo[3.4-dlpyrimidin-l-yl)-1.4-oxazepane-4- carboxylate tert-butyl 6-(4-amino-3-iodo-lH-pyrazolo[3,4-d]pyrimidin-l-yl)-l,4-oxazepane-4-carboxylate (1.18 mmol) is dissolved in ethylene glycol dimethylether (50 mL) and water (10 mL). 4,4,5,5- tetramethyl-2-(4-phenoxyphenyl)-l,3,2-dioxaborolane (1.47 mmol), palladium tetrakistriphenylphosphine (0.059 mmol) and sodium carbonate (2.95 mmol) are added and the reaction is heated for 12-20 hours. Additional boronate and palladium tetrakistriphenylphosphine are added and the reaction is heated at 60- 90 C for a further 20-24 hours. The reaction is concentrated under reduced pressure. The remaining residue was partitioned between dichloromethane and water. The organic layer is dried then concentrated under reduced pressure to yield the title comound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.7 g | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; ethanol; at 80℃; for 36h;Inert atmosphere; | 4,4,5,5-Tetramethyl-2-(4-phenoxyphenyl)-1,3,2-dioxaborolane (1.0 g, 3.38 mmol) was dissolved in ethylene glycol dimethyl ether (38 mL) and ethanol (11 mL), and 4-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexanone (0.5 g, 1.35 mmol), a saturated sodium carbonate solution (12 mL), and tetrakis(triphenylphosphine)palladium (0.1 g, 0.10 mmol) were sequentially added to the solution. The mixture was stirred all night and half a day in an argon atmosphere at 80C. After the mixture was left to cool naturally, the mixture was extracted by adding dichloromethane thereto, and the extract was partitioned and washed with saturated brine. The organic layer was dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. An oily substance thus obtained was purified by silica gel column chromatography (dichloromethane/methanol = 10/1 ? dichloromethane/methanol = 95/5), and thus 4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexanone (0.7 g) was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.6 g | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 80℃; | tert-Butyl 4-(4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)piperidine-1-carboxylate (0.7 g, 1.49 mmol) and <strong>[269410-26-6]<strong>[269410-26-6]4,4,5,5-tetramethyl-2-(4-phenoxyphenyl)-1,3,2-dioxaborolan</strong>e</strong> (0.5 mg, 1.79 mmol) were dissolved in ethylene glycol dimethyl ether (25 mL), and a saturated aqueous solution of sodium carbonate (5 mL) and tetrakis(triphenylphosphine)palladium (0.1 g, 0.10 mmol) were sequentially added thereto. The mixture was stirred overnight at 80C. After the mixture was left to cool naturally, water was added thereto, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (hexane/ethyl acetate = 3/1), and thus the title compound (yellow solid, 0.6 g) was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
5.22 g | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 80℃; for 3.5h; | 4-Phenoxyphenylboronic acid pinacol ester (8.44 g) was dissolved in ethylene glycol dimethyl ether (300 mL), and 4-chloro-7-(1,4-dioxaspiro[4.5]decan-8-yl)-5-iodo-7H-pyrrolo[2,3-d]pyrimidine (7.97 g), sodium carbonate (6.02 g), water (200 mL) and tetrakis(triphenylphosphine)palladium (1.32 g) were sequentially added to the solution. The mixture was stirred at 80C for 3.5 hours. The mixture was left to cool naturally, subsequently ethyl acetate (400 mL) was added thereto, and the mixture was partitioned. The organic layer was washed with water (250 mL) and saturated brine (250 mL) and dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. A pale brown oily substance (13.8 g) was obtained, and hexane/ethyl acetate (5 : 1, 40 mL) and dichloromethane (15 mL) were added thereto. A white solid precipitated therefrom was collected by filtration and dried, and thus 4-chloro-5-(4-phenoxyphenyl)-7-(1,4-dioxaspiro[4.5]decan-8-yl)-7H-pyrrolo[2,3-d]pyrimidin e (5.22 g) was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; at 100℃; for 1h; | A solution of (S)-methyl l-(8-amino-l-bromoimidazo[l,5-a]pyrazin-3- yl)piperidine-3-carboxylate (80 mg, 0.15 mmol) and 4,4,5, 5-tetramethyl-2-(4-phenoxyphenyl)- 1,3,2-dioxaborolane (65.5 mg, 0.3 mmol) in dioxane (1.5 mL) was added a solution of K2CO3(95.2mg,0.6 mmol ), pd(dppf)Cl2 (10.35 mg, 0.014mmol), then the mixture was heated at 100 C for lhour. After the raction,the mixture was cooled to room temperature and purified by pre-HPLC to give (S)-l-(8-amino-l-(4-phenoxyphenyl)imidazo[l,5-a]pyrazin-3-yl)piperidine-3- carboxylic acid . 1HNMR (400MHz, CDC13): delta= 13.79 (br. s., IH), 11.22 (br. s., IH), 8.26 - 8.15 (m, IH), 7.56 (d, J=8.5 Hz, 2H), 7.41 (t, J=7.5 Hz, 2H), 7.27 (s, IH), 7.21 (d, J=7.5 Hz, IH), 7.11 (dd, J=8.0, 16.1 Hz, 4H), 6.11 (br. s., IH), 4.00 - 3.88 (m, IH), 3.57 (d, J=l 1.5 Hz, IH), 3.24 (br. s., IH), 3.01 - 2.93 (m, IH), 2.85 (br. s., IH), 2.48 (d, J=11.5 Hz, IH), 1.77 (br. s., IH), 1.37 - 1.19 (m, IH) ppm. MS (ESI): M/Z (M+l)+= 429.5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bis-triphenylphosphine-palladium(II) chloride; caesium carbonate; In N,N-dimethyl-formamide; at 90℃; | Weigh 220 mg of the compound prepared in Step 1 tert-butyl 2-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)morpholinyl-4-carboxylate In a reaction flask, After adding 10 ml of DMF, 296 mg of <strong>[269410-26-6]4-phenoxybenzeneboronic acid pinacol ester</strong> was added, 17mg of bis(triphenylphosphine)palladium dichloride, 326 mg of cesium carbonate (Cs2C03), After stirring at 90 C until the reaction is complete,Add water to quench, Ethyl acetate extraction, dry, filter, concentrate, Column chromatography, The title compound was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
865.6 mg | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; ethanol; water; at 90℃; for 3h;Inert atmosphere; | Under nitrogen protection,To a solution of (S) -6- (8-amino-1-bromoimidazo [1,5-a] pyrazin-3-yl) -5-azaspiro [2.4] Ester (1 g, 2.45 mmol),4,4,5,5-tetramethyl-2- (4-phenoxyphenyl) -1,3,2-dioxaborolane (796.7 mg, 2.69 mmol)Na2CO3 (519.4 mg, 4.9 mmol)Of dioxane / EtOH / water (12 mL / 4 mL / 4 mL)In the mixed solution,Pd (PPh3) 4 (141.56 mg, 0.1225 mmol) was added,The reaction mixture was stirred for 3h at 90 ,TLC shows the raw material reaction is complete,The reaction solution was quenched by the addition of water,Extracted with EA (10 mL x 3)Organic phase with saturated salt water backwash,Anhydrous Na2SO4 dried,After evaporation in vacuo, the residue was purified by column chromatography (DCM / MeOH = 60/1 to 30/1)To give 865.6 mg of the title compound |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With n-butyllithium; In tetrahydrofuran; at -78 - -40℃; for 18h;Inert atmosphere; | 4-bromodiphenyl ether(6.2g, 25.0mmol) Isopropanol pinacol borate (10.3 mL, 50 mmol)Soluble in dry tetrahydrofuran,Cooled to -78C under nitrogen protection.n-Butyllithium (2.5M, 18 mL, 45 mmol) was added dropwise,After completion of the addition, the mixture was stirred for 6 hours and slowly warmed to -40C for 12 hours.The reaction was added to saturated ammonium chloride solution and extracted three times with ethyl acetate.The organic phases were combined and dried over anhydrous sodium sulfate.It was evaporated to dryness by rotary evaporation and purified by column to give 5.4 g of the target compound in a yield of 72%. |
Tags: 269410-26-6 synthesis path| 269410-26-6 SDS| 269410-26-6 COA| 269410-26-6 purity| 269410-26-6 application| 269410-26-6 NMR| 269410-26-6 COA| 269410-26-6 structure
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P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
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 |
Sorry,this product has been discontinued.
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