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Chemical Structure| 3554-65-2 Chemical Structure| 3554-65-2

Structure of 3554-65-2

Chemical Structure| 3554-65-2

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Product Details of [ 3554-65-2 ]

CAS No. :3554-65-2
Formula : C6H13NO
M.W : 115.17
SMILES Code : OCC1N(C)CCC1
MDL No. :MFCD06200823

Safety of [ 3554-65-2 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 3554-65-2 ] 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 36.81
TPSA ?

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

23.47 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.78
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

0.13
Log Po/w (WLOGP)?

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

-0.31
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

0.51
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.46

Water Solubility

Log S (ESOL):?

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

-0.57
Solubility 31.0 mg/ml ; 0.269 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.

-0.18
Solubility 76.3 mg/ml ; 0.662 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

-0.26
Solubility 63.9 mg/ml ; 0.555 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.

-6.91 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)

1.48

Application In Synthesis of [ 3554-65-2 ]

* 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 [ 3554-65-2 ]

[ 3554-65-2 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 498-63-5 ]
  • [ 74-88-4 ]
  • [ 3554-65-2 ]
YieldReaction ConditionsOperation in experiment
With n-butyllithium; In tetrahydrofuran; water; REFERENCE EXAMPLE 22 Five grams (0.050 mol) of <strong>[498-63-5]prolinol</strong> were treated with double the equivalent of n-butyl lithium in tetrahydrofuran at -70° C., and 7.0 g of methyl iodide was added dropwise thereto at -70° C., followed by stirring for 2 hours. The temperature was gradually elevated, and the reaction was further continued for an additional hours under ice-cooling. To the reaction mixture was added 1.8 g of water, and the precipitate thus formed was removed by filtration. The filtrate was concentrated, and the concentrate was purified by column chromatography to obtain 3.0 g of N-methyl<strong>[498-63-5]prolinol</strong>.
With n-butyllithium; In tetrahydrofuran; water; REFERENCE EXAMPLE 22 Five grams (0.050 mol) of <strong>[498-63-5]prolinol</strong> were treated with double the equivalent of n-butyl lithium in tetrahydrofuran at -70°C, and 7.0 g of methyl iodide was added dropwise thereto at -70°C, followed by stirring for 2 hours. The temperature was gradually elevated, and the reaction was further continued for an additional 2 hours under ice-cooling. To the reaction mixture was added 1.8 g of water, and the precipitate thus formed was removed by filtration. The filtrate was concentrated, and the concentrate was purified by column chromatography to obtain 3.0 g of N-methyl<strong>[498-63-5]prolinol</strong>.
  • 2
  • prolinol ester [ No CAS ]
  • [ 638-53-9 ]
  • [ 498-63-5 ]
  • [ 3554-65-2 ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate;toluene-4-sulfonic acid; In benzene; The resulting N-methyl<strong>[498-63-5]prolinol</strong> (3.0 g; 0.026 mol) was mixed with 5.6 g (0.026 mol) of tridecanoic acid, and a catalytic amount of p-toluenesulfonic acid was added thereto. The reaction mixture was azeotripically dehydrated in benzene for 3 hours. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, and the mixture was extracted with benzene. The benzene extract was washed successively with water and a saturated sodium chloride aqueous solution, and dried over sodium sulfate. The benzene was removed by distillation, and the residue was purified by column chromatography to obtain 6.1 g (yield: 39percent from <strong>[498-63-5]prolinol</strong>) of a <strong>[498-63-5]prolinol</strong> ester of formula (II) wherein R3 =CH3 and R4 =-(CH2)11 CH3.
With sodium hydrogencarbonate;toluene-4-sulfonic acid; In benzene; The resulting N-methyl<strong>[498-63-5]prolinol</strong> (3.0 g; 0.026 mol) was mixed with 5.6 g (0.026 mol) of tridecanoic acid, and a catalytic amount of p-toluenesulfonic acid was added thereto. The reaction mixture was azeotripically dehydrated in benzene for 3 hours. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, and the mixture was extracted with benzene. The benzene extract was washed successively with water and a saturated sodium chloride aqueous solution, and dried over sodium sulfate. The benzene was removed by distillation, and the residue was purified by column chromatography to obtain 6.1 g (yield: 39percent from <strong>[498-63-5]prolinol</strong>) of a <strong>[498-63-5]prolinol</strong> ester of formula (II) wherein R3 = CH3 and R4 = -(CH2)11CH3.
  • 3
  • [ 50-00-0 ]
  • [ 498-63-5 ]
  • [ 3554-65-2 ]
YieldReaction ConditionsOperation in experiment
56% With hydrogen;palladium 10% on activated carbon; In water; for 18h; a) (/?S)-(1 -Methylpyrrolidin-2-yl)methanoIA mixture of (RS)-pyrrolidin-2-ylmethanol (1.00 g, 9.90 mrnol, 1.0 eq), formaldehyde (35percent aqueous, 10 mL) and 10percent Pd/C (200 mg) was stirred under a balloon of hydrogen gas for 18 h. The mixture was filtered through a Celite pad, concentrated under reduced pressure and purification by silica gel chromatography (20percent MeOH/CHCI3) gave a colorless liquid (650 mg, 56percent); 1H NMR (400 MHz, CDCI3) 6 ppm 3.65 (dd, =10.0, 3.6 Hz, 1 H), 3.43 (dd, J=10.8, 2.0 Hz, 1H), 3.10-3.05 (m, 1 H), 2.40-2.35 (m, 1 H), 2.33 (s, 3H), 2.32-2.25 (m, 1 H), 1.93-1.68 (m, 4H); m/z (APCIf: 116 [M+H]+.
 

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