Structure of 221532-96-3
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CAS No. : | 221532-96-3 |
Formula : | C17H26N2O2 |
M.W : | 290.40 |
SMILES Code : | CC(C)(C)OC(=O)N1CCC(CC2=CC=C(N)C=C2)CC1 |
MDL No. : | MFCD08460890 |
InChI Key : | TYSWJDYRGCLWNZ-UHFFFAOYSA-N |
Pubchem ID : | 21876872 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 21 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.59 |
Num. rotatable bonds | 5 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 90.29 |
TPSA ? Topological Polar Surface Area: Calculated from |
55.56 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.16 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.13 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.09 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.69 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.44 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.9 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.49 |
Solubility | 0.0932 mg/ml ; 0.000321 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.97 |
Solubility | 0.0314 mg/ml ; 0.000108 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.83 |
Solubility | 0.043 mg/ml ; 0.000148 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) |
Yes |
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) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.85 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 |
1.0 alert |
Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.24 |
* 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 |
---|---|---|
With potassium carbonate; In butan-1-ol; | REFERENCE EXAMPLE 97 4-(4-Morpholinobenzyl)piperidine Hydrochloride 1-tert-Butoxycarbonyl-4-(4-aminobenzyl)piperidine (1 g, 3.45 mmol) was dissolved in 1-butanol (20 mL). To the solution were added bis(2-chloroethyl) ether (490 mg, 3.45 mmol) and potassium carbonate (1 g, 7.23 mmol), and the mixture was heated for 30 hours under reflux. The reaction mixture was poured into water (50 mL), and the mixture was extracted with ethyl acetate. The extract was washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the concentrate was purified by silica gel column chromatography (hexane/ethyl acetate=3/1) to give 1-tert-butoxycarbonyl-4-(4-morpholinobenzyl)piperidine (869 mg) as a colorless oily substance. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With iron(III) chloride; hydrazine hydrate; In methanol-tetrahydrofuran; | REFERENCE EXAMPLE 95-2 1-tert-Butoxycarbonyl-4-(4-aminobenzyl)piperidine To the solution of 1-tert-butoxycarbonyl-4-(4-nitrobenzyl)piperidine (4.53 g, 14.2 mmol) in methanol-tetrahydrofuran (1:1, 100 mL) were added activated carbon (2 g) and anhydrous ferric chloride (250 mg). To the mixture was added hydrazine monohydrate (5.64 mL), and the mixture was heated for 26 hours under ref lux. The reaction mixture was cooled to room temperature, the activated carbon was filtered off. The activated carbon was washed with metahnol. The filtrate and washings were combined, and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (hexane/ethyl acetate=2/3) to give the titled compound (4 g) as colorless powdery crystals. 1H NMR (CDCl3) delta 1.07-1.23 (2H, m), 1.45 (9H, s), 1.57-1.72 (3H, m), 2.42 (2H, d, J=6.0Hz), 2.56 (2H, d, J=13Hz), 3.57 (2H, br s), 4.06 (2H, d, J=13Hz), 6.61 (2H, d, J=8.4Hz), 6.92 (2H, d, J=8.4Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In tetrahydrofuran; | REFERENCE EXAMPLE 98-1 1-tert-Butoxycarbonyl-4-[4-(methylsulfonyl)aminobenzyl]piperidine 1-tert-Butoxycarbonyl-4-(4-aminobenzyl)piperidine (1.2 g, 4.15 mmol) was dissolved in tetrahydrofuran (20 mL). To the solution was added triethylamine (0.64 mL, 4.57 mmol). To the mixture was added dropwise methanesulfonyl chloride (0.39 mL, 4.95 mmol) under ice cooling, and the mixture was stirred under ice cooling for 30 minutes and at room temperature for 30 minutes. The reaction mixture was poured into ice-water (20 mL), and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the concentrate was purified by silica gel column chromatography (hexane/ethyl acetate=1/1) to give the titled compound (1.43 g) as colorless powdery crystals. 1H NMR (CDCl3) delta 1.19-1.63 (5H, m), 1.45 (9H, s), 2.50-2.81 (4H, m), 3.00 (3H, s), 4.02-4.15 (2H, m), 7.07-7.21 (5H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium chloride; sodium hydrogencarbonate; sodium nitrite; In water; acetic acid; | REFERENCE EXAMPLE 95-3 4-[4-(1H-Tetrazol-1-yl)benzyl]piperidine Hydrochloride To a solution of <strong>[221532-96-3]1-tert-butoxycarbonyl-4-(4-aminobenzyl)piperidine</strong> (1 g, 3.46 mmol) in acetic acid (14 mL) were added orthoethyl formate (2.4 mL, 20.7 mmol) and sodium azide (0.27 g, 4.13 mmol), and the mixture was stirred at room temperature for 30 minutes and at 80 C. for 2 hours. The mixture was cooled to room temperature. To the mixture were added water (20 mL) and a solution of sodium nitrite (4.3 g) in water (20 mL), and the mixture was stirred at room temperature for 10 minutes and extracted with ethyl acetate. The extract was washed with aqueous solution of sodium hydrogencarbonate and saturated sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the concentrate was purified by silica gel column chromatography (hexane/ethyl acetate=2/3) to give 1-tert-butoxycarbonyl-4-[4-(1H-tetrazol-1-yl)benzyl]piperidine (950 mg) as colorless powdery crystals. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | In tetrahydrofuran; | Step 1 A solution of 4-(piperidin-4-ylmethyl)-phenylamine (7.5 g, 39.44 mmol) in dry tetrahydrofuran (200 mL) was cooled in an ice bath under nitrogen atmosphere. Di-tert-butyl dicarbonate (9.76 g) was added to the solution in portions and stirred for 30 minutes. The resulting mixture was quenched with water, concentrated in vacuo, and extracted with ethyl acetate. The organic layer was washed with water and brine, dried, and solvents removed in vacuo. The crude product was chromatographed on a short silica gel column, eluding with 30% ethyl acetate/hexanes, to give 4-[1-(N-tert-butoxycarbonyl)piperidin-4-ylmethyl]-phenylamine (9.25 g, 81%) as an oil which solidifies, m.p. 91-92 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With methanol; potassium carbonate; at 20℃; for 16.0h; | K2CO3 (2N aqueous solution, 150 mL) was added to a solution of compound 94 (30.0 g, 78 mmol) in MeOH (300 mL), and the reaction was allowed to stir at room temperature for 16 h. The reaction mixture was concentrated in vacuo and the resulting residue was extracted with DCM (300 mL×2). The combined organics were dried over anhydrous MgSO4, and concentrated in vacuo to provide compound 95 as light brown syrup which solidified into a tan solid upon standing (24.6 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
tert-butyl4-( 4-aminobenzyl)piperidine-1-carboxylate; A solution of 2,2,2-trifluoro-N -( 4-(piperidin-4-ylmethyl)phenyl)acetamide (26.4 g, 9230 mmol) in dichloromethane (369 ml) was cooled to 0C and triethylamine (19.28 ml, 138mmol) was added slowly. To the resulting solution was added di-tert-butyl dicarbonate(22.14 g, 101 mmol) in dichloromethane (7 5 ml) via addition funnel over 10 minutes. The0C mixture was stirred for 2 hours and warmed slowly overnight. The reaction mixture wasrecooled to 0C, treated with 1 N sodium hydroxide (1 00 ml), warmed to room temperature and stirred for 1 hour. The bilayer was separated and the organics were washed with waterand brine, dried with magnesium sulfate, filtered and concentrated in vacuo. The residue waspurified by normal phase chromatography to give the title compound. | ||
With triethylamine; In dichloromethane; at 0℃; | A solution of 2,2,2-trifluoro-N-(4-(piperidin-4-ylmethyl)phenyl)acetamide (26.4 g, 92 mmol) in dichloromethane (369 ml) was cooled to 0 C. and triethylamine (19.28 ml, 138 mmol) was added slowly. To the resulting solution was added di-tert-butyl dicarbonate (22.14 g, 101 mmol) in dichloromethane (75 ml) via addition funnel over 10 minutes. The 0 C. mixture was stirred for 2 hours and warmed slowly overnight. The reaction mixture was recooled to 0 C., treated with 1 N sodium hydroxide (100 ml), warmed to room temperature and stirred for 1 hour. The bilayer was separated and the organics were washed with water and brine, dried with magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by normal phase chromatography to give the title compound. | |
A solution of 2,2,2-trifluoro-N-(4-(piperidin-4-ylmethyl)phenyl)acetamide (26.4 g, 92 mmol) in dichloromethane (369 ml) was cooled to 0 C. and triethylamine (19.28 ml, 138 mmol) was added slowly. To the resulting solution was added di-tert-butyl dicarbonate (22.14 g, 101 mmol) in dichloromethane (75 ml) via addition funnel over 10 minutes. The 0 C. mixture was stirred for 2 hours and warmed slowly overnight. The reaction mixture was recooled to 0 C., treated with 1 N aqueous sodium hydroxide (100 ml), warmed to room temperature and stirred for 1 hour. The bilayer was separated and the organics were washed with water and brine, dried with magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by normal phase chromatography to give the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With acetic acid; at 20℃; for 4.25h; | Cyclobutanone (1.54 mL, 20.6 mmol) was added to a solution of 4-(4-Amino-benzyl)-piperidine-1-carboxylic acid tert-butyl ester (3.0 g, 10.3 mmol) in Acetic acid (50 mL).The solution was stirred for 15 mm at room temperature before Sodium cyanide (1.01 g,20.6 mmol) was added and the reaction stirred for 4 h. The solution was concentratedunder reduced pressure. The resultant residue was partitioned between EA (75 mL) and 1M Na2CO3 (125 mL). The organic layer was further washed with brine (50 mL), dried over MgSO4, filtered and concentrated to dryness. Purification by chromatography over silica gel (gradient of EA in heptane from 0 to 50%) gave the pure product as an oily residue (2.82 g, 74%). ?H NIVIR (300 MHz, Chloroform-cl) 0.73 - 0.97 (m, 1H), 1.00 -1.19 (m, 2H), 1.20-1.34 (m, 1H), 1.45 (s, 9H), 1.61 (d, J= 11.4 Hz, 2H), 2.09-2.31 (m,2H), 2.31 - 2.41 (m, 2H), 2.44 (d, J= 6.8 Hz, 2H), 2.63 (t, J= 12.7 Hz, 2H), 2.72 - 2.89(m, 2H), 6.58 (d, J= 8.3 Hz, 2H), 7.00 (d, J= 8.3 Hz, 2H). C22H3,N302 MS m/z 270(M+H-B oc). |
Tags: 221532-96-3 synthesis path| 221532-96-3 SDS| 221532-96-3 COA| 221532-96-3 purity| 221532-96-3 application| 221532-96-3 NMR| 221532-96-3 COA| 221532-96-3 structure
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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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