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Chemical Structure| 4045-24-3 Chemical Structure| 4045-24-3

Structure of 4045-24-3

Chemical Structure| 4045-24-3

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Product Details of [ 4045-24-3 ]

CAS No. :4045-24-3
Formula : C6H13NO
M.W : 115.17
SMILES Code : COC1CCNCC1
MDL No. :MFCD04115010
InChI Key :ZEYSHALLPAKUHG-UHFFFAOYSA-N
Pubchem ID :77666

Safety of [ 4045-24-3 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H312-H332-H314
Precautionary Statements:P260-P264-P270-P271-P280-P301+P330+P331-P302+P352-P303+P361+P353-P304+P340-P305+P351+P338-P310-P363-P405-P501
Class:8
UN#:3267
Packing Group:

Computational Chemistry of [ 4045-24-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
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 36.64
TPSA ?

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

21.26 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.81
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

0.2
Log Po/w (WLOGP)?

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

0.0
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.

0.21
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

1.1
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.67

Water Solubility

Log S (ESOL):?

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

-0.61
Solubility 28.0 mg/ml ; 0.243 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.

-0.21
Solubility 71.8 mg/ml ; 0.623 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

-1.16
Solubility 7.95 mg/ml ; 0.069 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

Low
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.

-6.86 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)

1.0

Application In Synthesis of [ 4045-24-3 ]

* 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 [ 4045-24-3 ]

[ 4045-24-3 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 4045-24-3 ]
  • [ 335349-57-0 ]
  • [ 335349-83-2 ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate; In dimethyl sulfoxide; Example C5 [4-Iodo-5-(4-methoxy-piperidin-1-yl)-2-nitro-phenyl]-carbamic acid tert.-butyl ester Prepared from <strong>[335349-57-0]5-chloro-4-iodo-2-nitro-phenylamine</strong> (Example A1) (6.91 g, 23.15 mmol), 4-methoxypiperidine (4.0 g, 34.73 mmol) and NaHCO3 (5.83 g, 69.45 mmol) in DMSO (230 mL) at 100 C. according to the general procedure C (method b). The obtained brown solid (7.95 g) was converted to the title compound according to the general procedure B (method c). Obtained as a yellow solid (6.55 g). MS (ISP) 478 [(M+H)+]; mp 133-135 C.
  • 2
  • [ 4045-25-4 ]
  • [ 4045-24-3 ]
YieldReaction ConditionsOperation in experiment
With ammonia; In water;pH 10.0; 4-Methoxypiperidine (286). A mixture of terf-butyl 4-hydroxy-1-piperidinecarboxylate (284) (Dailewicz, J. C; et al., J. Med. Chem. 2002, 45, 2432-2453) (19.7 g, 98 mmol), crushed KOH (11.0 g, 196 mmol) and MeI (7.3 mL, 118 mmol) in DMSO (100 mL) was stirred at20 0C for 16 h under N2. The mixture was poured into water (500 mL) and extracted with Et2O (2 x 150 mL). The combined organic fraction was washed with water (2 x 50 mL), dried and the solvent evaporated to give methyl ether 285 (19.1 g, 91%) as a white solid: 1H NMR delta 3.71-3.78 (m, 2 H, CH2N), 3.31-3.39 (m, 4 H, CHO, OCH3), 3.06-3.12 (m, 2 H, CH2N), 1.80-1.85 (m, 2 H, CH2), 1.45-1.54 (m, 2 H, CH2), 1.43 [s, 9 H, C(CH3)3]. A solution of HCI in dioxane (4 M, 67 mL, 266 mmol) was added to a stirred solution of methyl ether 285 (19.1 g, 88.7 mmol) in dioxane (100 mL) and the mixture stirred at 20 0C for 96 h.The solvent was evaporated and the residue dried to give the amine hydrochoride 286 as a white solid: 1H NMR [(CD3)2SO] delta 8.99 (br s, 2 H, NH.HCI), 3.40-3.46 (m, 1 H, CHO), 3.25 (s, 3 H, OCH3), 3.07-3.12 (m, 2 H, CH2N)1 2.88-2.94 (m, 2 H, CH2N), 1.91- 1.99 (m, 2 H, CH2), 1.63-1.74 (m, 2 H, CH2). The hydrochloride was dissolved in water (50 mL), the pH adjusted to 10 with CNH3 and the mixture extracted with CHCI3 (4 x 50 mL) to give the free base, which was used without further purification.
  • 3
  • [ 4045-24-3 ]
  • [ 1010120-55-4 ]
  • [ 1202490-73-0 ]
YieldReaction ConditionsOperation in experiment
67% With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); XPhos; In N,N-dimethyl-formamide; at 180℃; for 0.25h;Microwave irradiation; A suspension of 5-bromo[l,2,4]triazolo[l,5-alpha]pyridin-2-amine (69.2 mg, 0.325 mmol, 1 equiv), 4-methoxypiperidine (150 mg, 1.3 mmol, 4.0 equiv), cesium carbonate (212 mg, 0.652 mmol, 2.00 equiv), XPhos (16.9 mg,0.0354 mmol, 0.109 equiv), and tris(dibenzylideneacetone)dipalladium (0) (9.3 mg, 0.010 mmol, 0.031 equiv) in N,7V-dimethylformamide (2 mL) was heated to 180 C in the microwave for 15 min. The reaction mixture was concentrated in vacuo. The resulting residue was partitioned between ethyl acetate (5 mL) and saturated aqueous sodium chloride solution (5 mL). The aqueous was extracted with ethyl acetate (2 x 5 mL). The combine organic was dried over anhydrous sodium sulfate, filtered, and concentrated. Purification by flash column chromotagraphy (95:5 dichloromethane / methanol) afforded a white solid (557 mg, 67%). LCMS (ESI) w/z:248.3. 1H NMR (500 MHz, CDCl3), delta: 7.32 (m, 1 H), 7.05 (m, 1 H), 6.23 (m, 1 H), 4.39(br s, 2 H), 3.66 (m, 2 H), 3.48 (m, 1 H), 3.41 (s, 3 H), 3.18 (m, 2 H), 2.08 (m, 2 H), 1.89 (m, 2 H).
 

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Technical Information

Categories

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