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CAS No. : | 20845-34-5 |
Formula : | C7H15NO |
M.W : | 129.20 |
SMILES Code : | C(C1N(CCCC1)C)O |
MDL No. : | MFCD00006494 |
InChI Key : | HXXJMMLIEYAFOZ-UHFFFAOYSA-N |
Pubchem ID : | 89394 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H227-H315-H319-H335 |
Precautionary Statements: | P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 41.62 |
TPSA ? Topological Polar Surface Area: Calculated from | 23.47 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from | 1.72 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by | 0.49 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from | 0.08 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from | 0.57 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by | 0.78 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | 0.73 |
Log S (ESOL):? ESOL: Topological method implemented from | -0.88 |
Solubility | 16.9 mg/ml ; 0.131 mol/l |
Class? Solubility class: Log S scale | Very soluble |
Log S (Ali)? Ali: Topological method implemented from | -0.55 |
Solubility | 36.2 mg/ml ; 0.28 mol/l |
Class? Solubility class: Log S scale | Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by | -0.55 |
Solubility | 36.2 mg/ml ; 0.28 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 | -6.74 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) | 1.66 |
* 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 triethylamine; In tetrahydrofuran; at 0 - 23℃; for 1.67h; | To a solution of 1 -methyl-2-piperidine-methanol (Aldrich, 0.27 mL, 2.1 mmol) in 10 mL tetrahydrofuran (THF) at 0 0C was added triethylamine (0.87 mL, 6.22 mmol) followed EPO <DP n="34"/>by methanesulfonyl chloride (0.24 mL, 3.1 mmol). The mixture was stirred at 0 0C for 10 min then the ice-bath was removed and the reaction mixture was stirred at 23 0C for an additional 1.5 h. The reaction mixture was filtered though Celite with THF and concentrated under reduced pressure. This crude material was used directly in the next reaction. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With LiAlH4; In tetrahydrofuran; | EXAMPLE 10 1-Methyl-2-piperidinemethanol The title compound of Example 9 (23.2 g, 101 mmol) in dry THF (100 mL) was added dropwise to a 1.0M solution of LiAlH4 in THF (405 mL, 405 mmol, 4eq) and the reaction mixture was refluxed overnight and the product was isolated as described in Example 6 to give the product (13.1 g, quantative) as a colorless oil. The fumarate salt crystallized from 2-propanol: mp 118°-120° C.; 1 H-NMR (CDCl3) dd;3.85 (dd, J=gem=11 Hz, J=3.9 Hz, 1H), 3,39 (dd, J=gem=11 Hz, J=2.2 Hz, 1H), 2.89 (m, 1H), 2.30 (s, 3H), 2.15 (m, 1H), 1.97 (m, 1H), 1.76 (m, 1H), 1.42-1.68 (complex m, 4H), 1.28 (m, 1H); CIMS (MH+ calcd for C7 H15 NO): 130. Found (MH+): 130; Anal. (C11 H19 NO5): C,H,N. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With 5percent silver supported on titanium oxide; at 25℃; for 10h;Inert atmosphere; Sealed tube; UV-irradiation; | General procedure: In a glass reaction vessel,2 mmol of 2- (benzylamino) ethanol, 45 mg of catalyst D,20 mL of dehydrated methanol, and a magnetic stirrer.Then, an argon gas was introduced into the sealed reaction system, and under a condition of 25 ° C.,While stirring the reaction system, ultraviolet rays were irradiated for 10 hours.When the reaction solution was subjected to GC-MS analysis,Only 2- (N-methylbenzylamino) ethanol was obtained(Yield 87percent, see Table 3). |
Then, a dichloromethane (30 ml) solution of (-)-1-methyl-2-piperidinemethanol (3.04 g, 23.8 mmol) produced in Reference Example 7 was dropwise added, and the mixture was stirred at -78° C. for 30 min. Triethylamine (22 ml, 150 mmol) was slowly dropped, and the mixture was stirred for 15 min. Temperature of the resulting mixture was raised to approximately 10° C. followed by addition of water (65 ml). The organic layer was separated, and the aqueous layer was extracted with chloroform (2*100 ml). The combined organic layers were washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to give a crude product as a brown oil (3.00 g). The crude aldehyde thus obtained was used immediately in the next step without any further purification. To a solution of the crude aldehyde (3.00 g, 33.8 mmol) in ether (100 ml) was dropwise added under ice-cooling a 1.0M ether solution of methylmagnesium iodide (25 ml, 25 mmol). Subsequently, the mixture was stirred at room temperature for 2 hours followed by addition of a saturated aqueous ammonium chloride (50 ml). The mixture was extracted with chloroform (2*100 ml), and the organic layers were washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. | ||
With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 20℃; for 3.16667h;Inert atmosphere; | General procedure: A solution of tert-butyl (3R)-3-(hydroxymethyl)piperidine-1-carboxylate (1.07 g,4.98 mmol) in dry THF (10 mL) was stirred under N2 and cooled in an ice-water bath. A 2M solution of LiA1H4 in THF (3.0 mL, 5.97 mmol) was added dropwise over a period of10 minutes. The mixture was stirred at 0 °C and gradually allowed to warm to roomtemperature over 3 hours. After stirring at room temperature overnight the mixture wascooled in an ice-bath and a 1 N solution of NaOH (1 mL) was added dropwise over a periodof 10 minutes followed by water (0.5 mL). The mixture was stirred at room temperature for 3 hours, filtered through a Celite® cartridge which was then washed through with THF and the combined filtrates were concentrated in vacuo to give the title product as a yellow oil(0.61 g, 95percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
31% | Step 11-Methylpiperidine-2-carbaldehydeDimethyl sulfoxide (3.3 mL, 46 mmol) was dissolved in 15 mL of dichloromethane in a dry ice bath, followed by dropwise slowly addition of oxalyl chloride (2.6 mL, 31 mmol).After stirring for 45 minutes, a solution of (1-methyl-2-piperidyl)methanol 6a (1 g, 7.74 mmol) in 5 mL of dichloromethane was added dropwise to the solution.The reaction mixture was stirred for 45 minutes, then added with triethylamine (7.2 mL, 52 mmol), and stirred for 10 minutes, then warmed up to room temperature and stirred for 1 hour.The reaction mixture was washed with water (20 mL) and saturated brine (20 mL) successively.The combined organic extracts were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure then the resulting residue was purified by alkaline alumina column chromatography with elution system A to obtain the title compound 1-methylpiperidine-2-carbaldehyde 6b (300 mg, yield 31.0percent) as a brown oil, which was directly used in the next step without purification. | |
DMSO (122 mg, 1.56 mmol) in DCM (0.5 mL) was cooled to -78°C, and trifluoroacetic acid anhydride (246 mg, 1.17 mmol) in DCM (0.5 mL) was added slowly. The mixture was stirred at -78°C for 45 min. Subsequently, a solution of (l-methylpiperidin-2-yl)methanol (101 mg, 0.78 mmol) in DCM (1.0 mL) was added dropwise, and the mixture was kept at -78°C for 1 h. Triethyl- amine (99 mg, 0.98 mmol) was added, and the mixture was slowly warmed to rt. The mixture was then diluted with tert-butyl methyl ether/DCM (1 :1) and extracted with 1 N hydrochloric acid. The aqueous phase was washed twice with tert-butyl methyl ether, then basifed with sodium carbonate <n="153"/>solution and extracted with tert-butyl methyl ether. The organic phase was dried over sodium sulfate, and the solvent was carefully removed in vacuo. The residue was dissolved in THF (1.0 mL) to give solution A. | ||
Under dry ice bath, dimethylsulfoxide (3.3 mL, 46 mmol) was dissolved in 15 mL of methylene chloride. It was slowly added dropwise oxalyl chloride (2.6 mL, 31 mmol). The reaction was stirred for 45 minutes. Add dropwise 5 mL (1-methyl-2-piperidine)methanol 6a (1 g, 7.74 mmol) in methylene chloride. The reaction was continued for 45 minutes. Add triethylamine (7.2 mL, 52 mmol). The reaction was stirred for 10 minutes. At room temperature react for one hour. The reaction mixture was washed successively with water (20 mL) and washed with saturated sodium chloride solution (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure, column chromatography using basic alumina A to the resulting residue was purified eluent system to give the title product, 1-methyl - piperidin-2-carbaldehyde 6b (300 mg, brown liquid), yield: 31.0percent, crude without purification directly to the next reaction. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
34% | With thionyl chloride; In chloroform; | EXAMPLE 4 1-Methyl-2-[(N-phenyl-N-2-indanyl)aminomethyl]piperidine HCI (TAC 29) Treatment of 1-methyl-2-piperidinemethanol (12.9 g, 0.1 mol) with thionyl chloride (7.6 ml) in chloroform (40 ml), as described in example 3, gave 1-methyl-2-(chloromethyl) piperidine (5.0 g, 34percent). |
14.1. 4-[(1-Methylazepan-3-yl)oxy]benzaldehyde and4-[(1-methylpiperidin-2-yl)methoxy]benzaldehyde To a solution of 2.59 g (21.2 mmol) 2-chloromethyl-1N-methylpiperidine (obtained by reacting 1N-methylpiperidine-2-ylmethanol with SOCl2, hydrolysis with N NaOH and then extraction with dichloromethane) and 3.13 g (21.2 mmol) of 4-hydroxybenzaldehyde in 42 mL of DMF are added 2.93 g (21.2 mmol) of potassium carbonate. The mixture is stirred at 80° C. for 4 hours and, after cooling, is then poured into water and extracted with ethyl acetate. The organic extract is washed with water and then with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and then evaporated under reduced pressure. 900 mg of the residue obtained are purified on a column of silica gel (solvent: dichloromethane/methanol from 100/0 to 95/5 (v/v)). 360 mg of 4-[(1-methylazepan-3-yl)oxy]benzaldehyde and 192 mg of 4-[(1-methylpiperidin-2-yl)methoxy]benzaldehyde are obtained. These products are oily.4-[(1-Methylazepan-3-yl)oxy]benzaldehyde:1H NMR (DMSO-d6, 400 MHz) delta ppm: 1.48-1.80 (m, 5H); 2.0-2.10 (m, 1H); 2.31 (s, 3H); 2.45-2.55 (m, 1H); 2.55-2.70 (m, 2H); 2.82-2.90 (m, 1H); 4.18-4.23 (m, 1H); 7.14 (d, J=9 Hz, 2H), 7.84 (d, J=9 Hz, 2H), 9.86 (s, 1H, CHO).4-[(1-Methylpiperidin-2-yl)methoxy]benzaldehyde:1H NMR (DMSO-d6, 400 MHz) delta ppm: 1.20-1.60 (m, 4H); 1.68-1.80 (m, 2H); 2.02-2.10 (m, 1H); 2.20-2.27 (m, 1H); 2.24 (s, 3H); 2.74-2.80 (m, 1H); 4.0-4.05 (m, 1H); 4.18-4.22 (m, 1H); 7.13 (d, J=9 Hz, 2H), 7.85 (d, J=9 Hz, 2H), 9.88 (s, 1H, CHO). |
Tags: 20845-34-5 synthesis path| 20845-34-5 SDS| 20845-34-5 COA| 20845-34-5 purity| 20845-34-5 application| 20845-34-5 NMR| 20845-34-5 COA| 20845-34-5 structure
A226507 [136030-04-1]
(S)-(1-Methylpiperidin-2-yl)methanol
Similarity: 1.00
A379132 [68474-13-5]
(R)-(1-Methylpiperidin-2-yl)methanol
Similarity: 1.00
A226507 [136030-04-1]
(S)-(1-Methylpiperidin-2-yl)methanol
Similarity: 1.00
A379132 [68474-13-5]
(R)-(1-Methylpiperidin-2-yl)methanol
Similarity: 1.00
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