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Chemical Structure| 90365-74-5 Chemical Structure| 90365-74-5

Structure of 90365-74-5

Chemical Structure| 90365-74-5

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Product Details of [ 90365-74-5 ]

CAS No. :90365-74-5
Formula : C11H15NO2
M.W : 193.24
SMILES Code : O[C@H]1CN(CC2=CC=CC=C2)C[C@@H]1O
MDL No. :MFCD01073893
InChI Key :QJRIUWQPJVPYSO-QWRGUYRKSA-N
Pubchem ID :2734057

Safety of [ 90365-74-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 90365-74-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 6
Fraction Csp3 0.45
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 57.66
TPSA ?

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

43.7 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.73
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

0.3
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.

0.58
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

0.83
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.63

Water Solubility

Log S (ESOL):?

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

-1.41
Solubility 7.48 mg/ml ; 0.0387 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.

-0.78
Solubility 32.1 mg/ml ; 0.166 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

-1.64
Solubility 4.43 mg/ml ; 0.0229 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.

-7.27 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)

1.97

Application In Synthesis of [ 90365-74-5 ]

* 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.

  • Upstream synthesis route of [ 90365-74-5 ]
  • Downstream synthetic route of [ 90365-74-5 ]

[ 90365-74-5 ] Synthesis Path-Upstream   1~1

  • 1
  • [ 90365-74-5 ]
  • [ 90481-32-6 ]
YieldReaction ConditionsOperation in experiment
99%
Stage #1: With hydrogen; acetic acid In ethanol at 20℃; for 7 h;
Stage #2: With hydrogenchloride In 1,4-dioxane
To a solution of (3S,4S)-1-benzylpynolidne-3,4-diol (522 mg) in ethanol (15 mL) were added 10percent palladium-carbon (100 mg) and acetic acid (10 mL), and the mixture was reacted under pressurized hydrogen (40psi) at room temperature for 7 hours in Parr hydrogenation apparatus. The reaction solution was filtered through Celite, and the filtrate was concentrated under reduced pressure. To the resulting residue was added 4N hydrochloric acid-dioxane solution, and then the mixture was concentrated under reduced pressure to give the titled compound (373 mg) as a yellow solid (yield 99percent). MS(APCI)m/z; 104[M+H]+.
90.9% With palladium 10% on activated carbon; hydrogen In ethanol; water at 20℃; for 48 h; Intermediate ((3S, 4S) -5) (77.3g, 0.4mol) was dissolved in 80percent aqueous ethanol (2.4L) was added 10percent Pd / C (7.0g), at room temperature through hydrogen (0.07MPa) reaction 2d. The catalyst was removed by filtration and the filtrate concentrated under reduced pressure, the residue was treated with absolute ethanol (2 × 250mL) with traces of water addition to give a yellow oil of Intermediate ((3S, 4S) -6) 37.5g, yield 90.9percent.
90.9% With palladium 10% on activated carbon; hydrogen In ethanol; water at 20℃; for 48 h; Intermediate ((3S,4S)-5) (77.3 g, 0.4 mol) was dissolved in an aqueous solution of ethanol (80percent), to which10percent Pd/C (7.0 g) was added. Hydrogen (0.07 MPa) was supplied, and the reaction was kept for 2 days at room temperature.The catalyst was filtered off, and the filtrate was concentrated under reduced pressure. Anhydrous ethanol(23250 mL) was used to remove the trace amount of water from the residue to obtain intermediate ((3S,4S)-6) as ayellow oil (37.5 g, yield: 90.9percent).MASS (ESI+) m/z = 104 (M+H)+.1 H NMR (400 MHz, DSO-d6): 2.60 (m, 2H), 3.02 (m, 2H), 3.83 (m, 2H), 4.81 (br s, 3H).
90.9% With palladium 10% on activated carbon; hydrogen In ethanol; water at 20℃; for 48 h; The intermediate ((3S, 4S)-5) (77.3 g, 0.4 mol) Soluble in 80percent aqueous ethanol solution (2.4L),Add 10percent Pd/C (7.0g),The reaction was carried out at room temperature with hydrogen (0.07 MPa) for 2 d.The catalyst was removed by filtration, and the filtrate was concentrated under reduced pressure.The residue was stripped of water with anhydrous ethanol (2×250 mL) to give a yellow oily intermediate ((3S, 4S)-6) 37.5 g, yield: 90.9percent.
83% With palladium 10% on activated carbon; hydrogen In ethanol at 20℃; for 24 h; General procedure: 10 percent Pd/C (1.50 g) was added to solution of 3a (7.50 g, 38.86 mmol) in ethanol (40 mL) under argon atmosphere, hydrogenated under 100 psi at room temperature for 24 h. The reaction mixture was filtered through celite pad, filtrate was evaporated in vacuo to get crude. The crude product was washed with n-pentane-diethyl ether mixture (1:1) (20 mL), decanted the organic layer and dried in vacuo yielding 3.28 g (82.0 percent) of light brown solid of compound 4a.

References: [1] Synthetic Communications, 2008, vol. 38, # 14, p. 2374 - 2384.
[2] Patent: EP2390254, 2011, A1, . Location in patent: Page/Page column 86.
[3] Bioorganic and Medicinal Chemistry Letters, 1999, vol. 9, # 16, p. 2385 - 2390.
[4] Angewandte Chemie, 1984, vol. 96, # 6, p. 425 - 426.
[5] Bioorganic and Medicinal Chemistry, 2007, vol. 15, # 12, p. 3965 - 3973.
[6] Tetrahedron, 2007, vol. 63, # 5, p. 1243 - 1253.
[7] Journal of Carbohydrate Chemistry, 2000, vol. 19, # 4-5, p. 585 - 601.
[8] Patent: CN105693520, 2016, A, . Location in patent: Paragraph 0154; 0155; 0156; 0157; 0158; 0159.
[9] Patent: EP3067351, 2016, A1, . Location in patent: Paragraph 0073; 0074.
[10] Patent: CN108658947, 2018, A, . Location in patent: Paragraph 0093; 0118; 0130-0132.
[11] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 12, p. 2818 - 2823.
[12] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 5, p. 1265 - 1268.
[13] Synthesis, 2006, # 2, p. 247 - 256.
[14] Patent: US2004/19065, 2004, A1, . Location in patent: Page/Page column 22.
[15] Synthesis, 2010, # 5, p. 791 - 796.
[16] Chemical Research in Toxicology, 2010, vol. 23, # 1, p. 118 - 133.
[17] Patent: US2012/295874, 2012, A1, . Location in patent: Page/Page column 170.
 

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