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Chemical Structure| 37951-49-8 Chemical Structure| 37951-49-8

Structure of 37951-49-8

Chemical Structure| 37951-49-8

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Product Details of [ 37951-49-8 ]

CAS No. :37951-49-8
Formula : C10H12O2
M.W : 164.20
SMILES Code : COC1=CC=CC(=C1)C(CC)=O
MDL No. :MFCD08458823
Boiling Point : No data available
InChI Key :LPDJHUUWTGXTCU-UHFFFAOYSA-N
Pubchem ID :584765

Safety of [ 37951-49-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 37951-49-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.3
Num. rotatable bonds 3
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 47.94
TPSA ?

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

26.3 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.24
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

2.31
Log Po/w (WLOGP)?

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

2.29
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.

1.74
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

2.51
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.22

Water Solubility

Log S (ESOL):?

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

-2.49
Solubility 0.537 mg/ml ; 0.00327 mol/l
Class?

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

Soluble
Log S (Ali)?

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

-2.5
Solubility 0.519 mg/ml ; 0.00316 mol/l
Class?

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

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

-3.26
Solubility 0.0911 mg/ml ; 0.000555 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

Yes
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

Yes
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.

-5.66 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)

1.33

Application In Synthesis of [ 37951-49-8 ]

* 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.

  • Upstream synthesis route of [ 37951-49-8 ]
  • Downstream synthetic route of [ 37951-49-8 ]

[ 37951-49-8 ] Synthesis Path-Upstream   1~2

  • 1
  • [ 50-00-0 ]
  • [ 37951-49-8 ]
  • [ 506-59-2 ]
  • [ 850222-40-1 ]
YieldReaction ConditionsOperation in experiment
78% With hydrogenchloride; <i>L</i>-proline In ethanol; water for 16 h; Reflux; Inert atmosphere A solution of 164.2 g of methoxyphenylacetone (compound of formula IV), 244.6 g of dimethylamine hydrochloride, 90 g of paraformaldehyde and 9.9 g of a 37percent aqueous hydrochloric acid solution was dissolved in 200 mL of ethanol and 34.5 g of L - the proline and the mixed reaction were heated to reflux under nitrogen. After the reaction was refluxed for 16 hours, the mixture was cooled to room temperature. The solvent was distilled off under reduced pressure. The residue was dissolved in water and the concentrated aqueous solution was adjusted to pH And the dichloromethane was washed three times. After the organic layers were combined, the mixture was washed once with dilute aqueous ammonia, dried over anhydrous Na2S04, filtered and dried to give pale yellow oil: (S) -3-dimethylamino- 1-methoxyphenyl-1-propanone (172.6 g, molar yield 78percent, HPLC purity 98percent, ee = 95percent); used directly in the next step. 1 ^ _ESI (m / z): 222.1 (M + H) +
References: [1] Patent: CN104803861, 2017, B, . Location in patent: Paragraph 0084; 0085.
  • 2
  • [ 50-00-0 ]
  • [ 37951-49-8 ]
  • [ 124-40-3 ]
  • [ 850222-40-1 ]
YieldReaction ConditionsOperation in experiment
306.2 g With <i>L</i>-proline In ethanol at 77℃; for 36 h; In a reaction flask, add m-methoxyphenylpropan-1-one 262.4g (1.6 mol), paraformaldehyde 96g (3.2 mol), L-proline 184g (1.6 mol), dimethylamine 144g (3.2 mol), ethanol 850 ml, stirring and dissolving, heating up to 77 °C reflux reaction for 36 hours, TLC monitoring raw material is fully converted to product (developing solvent: ethyl acetate: hexane=1:3). Reaction finishes, turns on lathe does reaction solvent, adding 10percent hydrochloric acid 1300 ml dissolved, add dichloromethane 500 ml extraction three times, the organic layer for recovering raw material, the water layer is 10percent sodium hydroxide 1400 ml adjusting PH value to 10 the left and the right, adding 500 ml methylene chloride extraction three times, the combined organic layer, washed to neutral, anhydrous sodium sulfate drying, to remove the drying agent, the filtrate concentrated under reduced pressure to free until the slips away the thing, shall be the oil of 329.5g, yield 93.2percent, ee value of 97percent.
Refinement of Compound 1
The compound 1 329.5g (1.49 mol), L - dibenzoyl tartaric acid 533.4g (1.49 mol) soluble in 2966 ml in acetone, with the temperature rising to 40 °C left stirring for 24 hours, the temperature slowly drops to 5 °C the left and the right, stirring brilliantly 4h, filtering, to get the solid 810.9g. Solid soluble in 2500 ml water, 10percent NaOH to adjust the PH value to 9 - 10, by adding dichloromethane 1000 ml extraction three times, the combined organic layer, washed to neutral, anhydrous sodium sulfate drying, filtering, turns on lathe does solvent to obtain oil object 306.2g, yield 93percent. the value of the ee 99.5percent.
References: [1] Patent: CN106278915, 2017, A, . Location in patent: Paragraph 0017; 0018; 0019; 0020.
 

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