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Chemical Structure| 3218-36-8 Chemical Structure| 3218-36-8

Structure of 3218-36-8

Chemical Structure| 3218-36-8

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Product Details of [ 3218-36-8 ]

CAS No. :3218-36-8
Formula : C13H10O
M.W : 182.22
SMILES Code : O=CC1=CC=C(C2=CC=CC=C2)C=C1
MDL No. :MFCD00006947
InChI Key :ISDBWOPVZKNQDW-UHFFFAOYSA-N
Pubchem ID :76689

Safety of [ 3218-36-8 ]

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

Computational Chemistry of [ 3218-36-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 12
Fraction Csp3 0.0
Num. rotatable bonds 2
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 57.27
TPSA ?

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

17.07 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.02
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

3.0
Log Po/w (WLOGP)?

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

3.17
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.

3.0
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

3.72
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.98

Water Solubility

Log S (ESOL):?

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

-3.36
Solubility 0.0792 mg/ml ; 0.000434 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.

-3.02
Solubility 0.173 mg/ml ; 0.000949 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

-4.86
Solubility 0.0025 mg/ml ; 0.0000137 mol/l
Class?

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

Moderately 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

Yes
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.

-5.28 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

2.0
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

1.0 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)

1.24

Application In Synthesis of [ 3218-36-8 ]

* 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 [ 3218-36-8 ]

[ 3218-36-8 ] Synthesis Path-Downstream   1~19

  • 1
  • [ 14447-15-5 ]
  • [ 3218-36-8 ]
  • [ 129179-91-5 ]
  • 2
  • [ 2346-00-1 ]
  • [ 3218-36-8 ]
  • [ 370593-44-5 ]
  • 4
  • [ 3218-36-8 ]
  • [ 133773-29-2 ]
  • [ 323179-27-7 ]
YieldReaction ConditionsOperation in experiment
72.9% With hydrogenchloride; sodium hydroxide; sodium borohydrid; In methanol; tert-butyl methyl ether; water; Example 33 7.06 g (37.1 mol) of (R)-2,4-dichloro-alpha-methylbenzylamine and 8.13 g (44.6 mmol) of 4-phenylbenzaldehyde were mixed in 50 ml of t-butyl methyl ether and stirred at room temperature for 1 hour. After ascertaining the disappearance of the amine, 30 ml of methanol was added thereto and 2.60 g (68.7 mmol) of sodium borohydride was gradually added at room temperature and stirred at room temperature for 16 hours. After the reaction, 13 ml of 36% hydrochloric acid and 10 ml of water were added at room temperature and evaporated under reduced pressure to yield crystals. To the obtained crystals was added 25 ml of t-butyl methyl ether, stirred and separated the crystals by filtration. The crystals were washed with 50 ml of t-butyl methyl ether and then mixed with alkaline solution containing 2.87 g of sodium hydroxide in 100 ml of water and extracted with 800 ml of t-butyl methyl ether under alkaline condition. The extract was evaporated under reduced pressure to yield 9.65 g (27.1 mmol) of (R)-N-(4-phenylbenzyl)-2,4dichloro-alpha-methylbenzylamine. (Yield: 72.9%, Purity 99.1%); NMR spectrum data (delta ppm, CDCl3); 1.34 (d) 3H; 1.60 (s) 1H; 3.64 (s) 2H; 4.32 (q) 1H; 7.25-7.62 (m) 12H.
  • 5
  • [ 20388-87-8 ]
  • [ 3218-36-8 ]
  • [ 175708-57-3 ]
  • (S)-[1-{Biphenyl-4-ylmethyl-[(2-phenyl-propylcarbamoyl)-methyl]-carbamoyl}-2-(1H-imidazole-4-yl)-ethyl]-carbamic acid benzyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
33% EXAMPLE 51 (S)-[1-{Biphenyl-4-ylmethyl-[(2-phenyl-propylcarbamoyl)-methyl]-carbamoyl}-2-(1H-imidazole-4-yl)-ethyl]-carbamic Acid Benzyl Ester The title compound can be prepared according to Example 15, Step 1, by substituting p-phenyl-benzaldehyde for 4-benzyloxy-benzaldehyde and in Step 5, by substituting beta-methyl-phenethylamine hydrochloride for beta,beta-dimethylphenethylamine hydrochloride. The title compound was obtained as a white foam (33%); ES-MS 630 (m+1).
  • 6
  • [ 120-35-4 ]
  • [ 3218-36-8 ]
  • 3-[(Biphenyl-4-ylmethyl)-amino]-4-methoxy-N-phenyl-benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Example 236 3-[(Biphenyl-4-ylmethyl)-amino]-4-methoxy-N-phenyl-benzamide The title compound has been made using the procedure of Example 50, but using 3-amino-4-methoxy-N-phenyl benzamide and 4-phenylbenzaldehyde as starting materials, which are commercially available from Aldrich; m.p. 222-223 C.
  • 7
  • [ 35661-51-9 ]
  • [ 3218-36-8 ]
  • [ 1158960-23-6 ]
  • 9
  • [ 15862-94-9 ]
  • [ 3218-36-8 ]
  • [ 1584706-26-2 ]
YieldReaction ConditionsOperation in experiment
70% General procedure: All materials were dried for one day at 120 C. Chloride and carbonyl derivatives were introduced into a Schlenk of 30 mL. Products were put in vacuo, then under nitrogen. An appropriate volume of anhydrous DMF was added after 10 min of nitrogen bubbling. The solution was vigorously stirred for 20 min at -20 C. TDAE was added slowly under inert atmosphere. The reaction was stirred for one hour. The second reaction phase was performed at rt or at temperature according to procedure of synthesis. The reaction was hydrolysed with distilled water after TLC analysis clearly showed that the chloride 1 had been totally consumed. The aqueous solution was extracted with dichloromethane and the combined organic layers washed with brine then dried on MgSO4.
  • 10
  • [ 221044-05-9 ]
  • [ 3218-36-8 ]
  • [1,1'-biphenyl]-4-yl(1-(pyrimidin-2-yl)-1H-indol-2-yl)methanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
72% With tert.-butylhydroperoxide; palladium diacetate; In decane; ethyl acetate; at 125℃; for 24h;Inert atmosphere; General procedure: To a 25-mL sealed tube were added indole (0.3 mmol), aldehyde (0.45 mmol), Pd(OAc)2 (6.72 mg,10 mmol%), TBHP (anhydrous, about 5M in decane) (4 equiv), EtOAc (2.0 mL). The tube wascapped and stirred under N2 at 125 C for 24 h. The reaction mixture was cooled to roomtemperature and diluted with CH2Cl2, filtered through a short pad of Celite, washed with brine andCH2Cl2 .The combined organic extracts were dried over Na2SO4, concentrated in vacuum, and theresulting residue was purified by silica gel column chromatography to afford the desired product.All compounds are characterized by 1H NMR, 13C NMR, LRMS/HRMS and their comparison toliterature values
  • 11
  • [ 57508-48-2 ]
  • [ 126-81-8 ]
  • [ 3218-36-8 ]
  • ethyl 2-amino-4-(biphenyl-4-yl)-7,7-dimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
12% With sodium ethanolate; In ethanol; at 80℃; for 0.833333h; General procedure: In a round bottom flask 1 eq. of dimedone, 1 eq of the desired aldehyde and 1 eq of <strong>[57508-48-2]ethyl 3-amino-3-iminopropionate hydrochloride</strong> were suspended in dry EtOH (2.5 mL/mmol) and heated at 80 C. To this solution 1 eq of a 0.5 M sodium ethanolate solution was added over the period of 20 min. After heating for further 30 min under reflux the reaction was cooled to 0 C and water (40 mL/mmol) was added. The aqueous solution was extracted with EtOAc (5×20 mL/mmol). The combined organic layers were washed with brine, dried with MgSO4 and the solvent was evaporated under reduced pressure. The crude material was purified by recrystallization from ethanol.
  • 12
  • [ 141-97-9 ]
  • [ 3218-36-8 ]
  • [ 50607-30-2 ]
  • ethyl 4-(biphenyl-4-yl)-2-methyl-5-oxo-1,4,5,6,7,8-hexahydro[1,6]naphthyridine-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
36% With ammonium acetate; iodine; acetic acid; In ethanol; at 60 - 80℃; for 72h;Inert atmosphere; General procedure: 1 eq. of a cyclic 1,3-dicarbonyl compound 2, 1 eq. of the desired aldehyde 5, 1.2 eq. of a 1,3-dicarbonyl compound 3, 1.5 eq. of dried NH4OAc, 0.3 eq. of iodine and a few drops of concentrated acetic acid were stirred in EtOH (2.5 mL/mmol) under Ar at 60?80 °C. The progress of the reaction was monitored via TLC. Upon completion of the reaction the solvent was evaporated and the residue was dissolved in EtOAc. The organic layer was washed twice with a saturated NaS2O3 solution and brine, dried over MgSO4 and concentrated under reduced pressure. The crude material was purified by recrystallization or flash chromatography.
  • 13
  • [ 78364-55-3 ]
  • [ 3218-36-8 ]
  • 6-fluoro-2-[2-((1,1'-biphenyl)-4-ylmethylene)hydrazino]benzothiazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
71% With acetic acid; In ethanol; at 80℃; for 0.166667h;Microwave irradiation; General procedure: A mixture of compound 2 (0.0549 g, 0.0003 mol), the appropriate aromatic aldehyde (0.00033 mol) and glacial acetic acid (0.1 mL) in ethanol (5 mL) was heated under microwave (20 W) at 80 °C for 10 min. On cooling, the precipitated solid was collected by filtration, washed with water, dried and crystallized to give compounds 3-29.
  • 14
  • [ 34800-90-3 ]
  • [ 3218-36-8 ]
  • N'-[biphenyl-4-ylmethylidene]-2-(naphthalen-1-yl)acetohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
76% In ethanol; for 3h;Reflux; General procedure: These compounds were prepared by refluxing substituted acetohydrazides 3(a-b) with 4-(benzyloxy) benzaldehyde (0.01 mol) in 20 mL of ethanol for 3 h. On cooling the reaction mixture to room temperature, a solid product appeared. The respective crude product was recrystallized using ethanol. N'-[Biphenyl-4-ylmethylidene]-<strong>[34800-90-3]2-(naphthalen-1-yl)acetohydrazide</strong> (5d). The final product was obtained as a white solid with 76% yield. m.p. 210-212 C. IR (KBr): numax (cm-1), 3228 (NH), 3037 (Ar C-H), 2897 (C-H), 1656 (C=O), 1610 (C=N), 1534(C=C). 1H-NMR (400 MHz, DMSO-d6): delta ppm, 4.97 (2H, s,H-1), 7.03-8.00 (16H, m, Ar-H), 8.11 (1H, s, H-5), 12.57 (1H, s, H-3). 13C-NMR (100 MHz, DMSO): delta ppm, 174.06 (amide C=O, C-2), 148.35 (N=CH, C-5), (aromatic C?s), 28.74 (naphthyl-CH2, C-1). LCMS (m/z): 365(M++1). Calcd. for C25H20N2O: C, 82.39; H, 5.53; N, 7.69; Found: C, 82.37; H, 5.55; N, 7.67 %.
76% In ethanol; for 3h;Reflux; General procedure: These compounds were prepared by refluxing substituted acetohydrazides 3(a-b) with 4-(benzyloxy) benzaldehyde (0.01 mol) in 20 mL of ethanol for 3 h. On cooling the reaction mixture to room temperature, a solid product appeared. The respective crude product was recrystallized using ethanol.
  • 15
  • [ 85822-16-8 ]
  • potassium phenyltrifluoborate [ No CAS ]
  • [ 3218-36-8 ]
  • 16
  • [ 1986-47-6 ]
  • [ 3218-36-8 ]
  • (1S*,2R*)-N-([1,1’-biphenyl]-4-ylmethyl)-2-phenylcyclopropan-1-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
13% General procedure: Trans-2-phenylcyclopropylamine hydrochloride (1.0 eq.), acetic acid (1.0eq.) and the appropriate aldehyde (0.9 eq.) were dissolved in around bottom flask in 10 mL dry DCE. The reaction mixture was stirred gently at room temperature for 2 h before sodium triacetoxyborohydride (3.0 eq.) was added in small portions to the reaction vessel. The reaction was monitored by TLC and quenched using 10 mL of an aqueous (5%) NaHCO3 solution. The organic layer was separated and the aqueous layer extracted three times with10 mL of DCE. All organic layers were combined, dried over anhydrous Na2SO4, concentrated in vacuo and purified using flash chromatography (silica gel; cyclohexane/ethyl acetate) to give the desired compound.
  • 17
  • [ 3218-36-8 ]
  • [ 32340-38-8 ]
  • 18
  • [ 16155-03-6 ]
  • [ 3218-36-8 ]
  • 2-([1,1'-biphenyl]-4-ylmethyl)-4-methyl-1-(4-nitrophenyl)piperazine [ No CAS ]
  • 19
  • [ 72824-04-5 ]
  • [ 3218-36-8 ]
  • [ 13211-01-3 ]
 

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