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Chemical Structure| 1125551-75-8 Chemical Structure| 1125551-75-8

Structure of 1125551-75-8

Chemical Structure| 1125551-75-8

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Product Details of [ 1125551-75-8 ]

CAS No. :1125551-75-8
Formula : C6H14ClNO
M.W : 151.63
SMILES Code : OC[C@@H]1CNCCC1.[H]Cl
English Name :(S)-Piperidin-3-ylmethanol hydrochloride
MDL No. :MFCD14155681
InChI Key :VLFTUQPTEOPYGV-RGMNGODLSA-N
Pubchem ID :70700777

Safety of [ 1125551-75-8 ]

Computational Chemistry of [ 1125551-75-8 ] Show Less

Physicochemical Properties

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 2.0
Molar Refractivity 43.69
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

32.26 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

0.0
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

0.66
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

0.4
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

0.57
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

0.96
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.52

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-1.13
Solubility 11.2 mg/ml ; 0.0741 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-0.91
Solubility 18.5 mg/ml ; 0.122 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-0.86
Solubility 20.8 mg/ml ; 0.137 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

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)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.76 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

1.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

0.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.65

Application In Synthesis of [ 1125551-75-8 ]

* 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.

  • Downstream synthetic route of [ 1125551-75-8 ]

[ 1125551-75-8 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 1174632-70-2 ]
  • [ 1436426-21-9 ]
  • [ 1125551-75-8 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Stage #1: 4-(bromomethyl)-2,3-difluorobenzoic acid With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 20℃; for 1h; Stage #2: 4-chloro-2-(4-(3,3,3-trifluoropropyl)piperazin-1-yl)aniline With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 1h; Cooling with ice; Stage #3: [(3S)-3-piperidinyl]methanol hydrochloride Further stages; 1.237 Example 1.237: Preparation of (S)-N-(4-Chloro-2-(4-(3,3,3-trifluoropropyl)piperazin-l- yl)phenyl)-2,3-difluoro-4-((3-(hydroxymethyl)piperidin-l-yl)methyl)benzamide (Compound 251). 4-(Bromomethyl)-2,3-difluorobenzoic acid (10 g, 39.8 mmol) was suspended in DCM (60 mL). Oxalyl chloride (3.49 mL, 39.8 mmol) was added at room temperature, followed by DMF (100 μ). The reaction was stirred at room temperature for 1 h. Then the solvent was removed and the resulting dark-purple oil was re-dissolved in DCM (50 mL). The mixture was cooled on ice and DIEA (13.92 mL, 80 mmol) and 4-chloro-2-(4-(3,3,3- trifluoropropyl)piperazin-l-yl)aniline (12.26 g, 39.8 mmol) were added. The reaction was warmed to room temperature and stirred for 1 h. The resulting reaction mixture was purified by column chromatography (0,5, 10% EtOAc/hexanes) to give the title compounds (9.04 g, 45.7%). LCMS (peak 1) m/z = 540.3 [M+H]+, (peak 2) m/z = 496.3 [M+H]+; 1H NMR (400 MHz, DMSO-i ) δ ppm 2.45-2.55 (m, 2H), 2.54-2.68 (m, 6H), 2.89 (t, = 4.42 Hz, 4H), 4.79 (s, 0.5H), 4.91 (s, 1.5H), 7.23 (dd, = 8.72, 2.27 Hz, 1H), 7.33 (d, = 1.89 Hz, 1H), 7.53 (t, = 6.88 Hz, 1H), 7.71 (q, = 7.37 Hz, 1H), 8.20 (d, = 8.59 Hz, 1H), 9.78 (d, = 6.95 Hz, 1H). Intermediate 1 (10 mg, 0.020 mmol), (S)-piperidin-3-ylmethanol hydrochloride (3.67 mg, 0.024 mmol), and DIEA (10.56 μ,, 0.060 mmol) were added to a vial with DMF (0.3 mL). The reaction was stirred with heating to 80 °C for 2 h. After this time, the reaction was fairly complete. The reaction mixture was purified by preparative HPLC (5-70% ACN/H20, 30 min), and then converted to its corresponding HCl salt by re-dissolving the material in ACN (0.2 mL) and H20 (0.8 mL), and adding HCl (4 eq.). The reaction was stirred at room temperature for 1 h. Then the reaction was frozen and lyophilized to yield the title compound (13.0 mg, 99%). LC/MS m/z = 575.4 [M+H]+; lU NMR (400 MHz, DMSO-i/6) δ ppm 1.02-1.24 (m, 1H), 1.67 (d, 7 = 13.99 Hz, 1H), 1.73-1.90 (m, 2H), 1.92-2.09 (m, 1H), 2.62-2.85 (m, 1H), 2.85-3.06 (m, 4H), 3.06-3.31 (m, 9H), 3.51-3.83 (m, 5H), 4.46 (s, 2H), 7.29 (d, 7 = 8.39 Hz, 1H), 7.35 (s, 1H), 7.59- 7.83 (m, 2H), 8.12 (d, 7 = 7.63 Hz, 1H), 9.84 (s, 1H), 10.46-10.68 (m, 1H).
  • 2
  • [ 1125551-75-8 ]
  • [ 108-12-3 ]
  • [ 1554631-83-2 ]
YieldReaction ConditionsOperation in experiment
94% Stage #1: [(3S)-3-piperidinyl]methanol hydrochloride With sodium hydroxide In water at 0℃; for 0.25h; Stage #2: isopentanoyl chloride In tetrahydrofuran; water at 0 - 20℃; 5d Example 5d: (S)-1-(3-(hydroxymethyl)piperidin-1-yl)-3-methylbutan-1-one (S)-piperidin-3-ylmethanol hydrochloride (lOg, 65.95mmol) in water (25 mL) wastreated dropwise at ooc with a solution ofNaOH (13.2 g, 330mmol, 5 eq.) in water (25 mL).The mixture was stirred for 15 min and a solution ofisovaleryl chloride (15.90 g, 131.920 mmol, 2eq.) in anhydrous THF (25 mL) was added dropwise while stirring vigorously. After30 minutes at ooc the reaction was slowly warmed up to room temperature and stirredovernight. Et20 (500 mL) was added to the reaction mixture with vigorous stirring. Theorganic layer was separed and washed with brine, dried over Na2S04 and concentrated togive a residue that was purified by chromatography on silica (Hex/EtOAc 0 - 100 to yield the25 desired compound as a colorless oil (16.27g, 82.62mmol, 94%). IH NMR (400 MHz,DMSO-d6, 20°C) 8 0.88 (pseudo d, J = 6.4 Hz, 6H), 1.06-1.75 (m, 5H), 1.88-2.05 (m, IH),2.07-2.23 (m, 2H), 2.30 (dd, J = 10.8, 12.8 Hz, 0.5H), 2.64 (ddd, J = 3.2, 10.8, 13.2 Hz,0.5H), 2.78 (dd, J = 10.4, 13.2 Hz, 0.5H), 2.93 (ddd, J = 2.4, 11.6, 13.6 Hz, 0.5H), 3.14-3.35(m, 2H), 3.70-3.85 (m, 1H), 4.08-4.18 (dm, 0.5H), 4.31-4.40 (dm, 0.5H), 4.49 (t, J = 5.2 Hz,0.5H), 4.58 (t, J = 5.2 Hz, 0.5H). MS 200 (MH+).
  • 3
  • [ 1125551-75-8 ]
  • [ 103-40-2 ]
  • [ 2280839-64-5 ]
YieldReaction ConditionsOperation in experiment
200 mg With N-ethyl-N,N-diisopropylamine; bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate In chloroform at 20℃; for 17h; 80-1 (Phenylmethyl) 4-[(3S)-3-(hydroxymethyl)-1-piperidinyl]-4-oxobutanoate Reference Example 80-1 (Phenylmethyl) 4-[(3S)-3-(hydroxymethyl)-1-piperidinyl]-4-oxobutanoate To a solution of 4-oxo-4-phenylmethoxybutanoic acid (100 mg) and [(3S)-3-piperidinyl]methanol hydrochloride (73 mg) in chloroform (4.8 mL), N,N-diisopropylethylamine (0.17 mL) and bromotripyrrolidinophosphonium hexafluorophosphate (223 mg) were added, and the mixture was stirred at room temperature for 17 hours. A saturated aqueous solution of sodium hydrogen carbonate (5 mL) was added to stop the reaction. The resultant mixture was extracted with ethyl acetate, and the organic layer was passed through a phase separator, and then concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-hexane: ethyl acetate = 10:1 to 1:1) to give the title compound (200 mg) as a colorless oil. MS ESI/APCI Multi posi: 306[M+H]+.
 

Historical Records

Technical Information

Categories

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