68089-73-6|9H-Tribenzo[a,c,e][7]annulen-9-one| Ambeed

CAS No. :	68089-73-6
Formula :	C₁₉H₁₂O
M.W :	256.30
SMILES Code :	O=C1C2=CC=CC=C2C3=CC=CC=C3C4=CC=CC=C41
MDL No. :	MFCD02114133
InChI Key :	XJROVMTUTAVKMP-UHFFFAOYSA-N
Pubchem ID :	12437220

Safety of [ 68089-73-6 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P280-P301+P312-P302+P352-P305+P351+P338

Computational Chemistry of [ 68089-73-6 ] Show Less

Physicochemical Properties

Num. heavy atoms	20
Num. arom. heavy atoms	19
Fraction Csp3	0.0
Num. rotatable bonds	0
Num. H-bond acceptors	1.0
Num. H-bond donors	0.0
Molar Refractivity	85.23
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	17.07 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.57
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	5.21
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	4.51
Log P_o/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.	3.72
Log P_o/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	5.11
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	4.22

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-5.41
Solubility	0.000987 mg/ml ; 0.00000385 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-5.32
Solubility	0.00124 mg/ml ; 0.00000483 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately 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	-7.75
Solubility	0.00000454 mg/ml ; 0.0000000177 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Poorly 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.	-4.16 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	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)	1.7

Application In Synthesis of [ 68089-73-6 ]

* 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 [ 68089-73-6 ]

[ 68089-73-6 ] Synthesis Path-Downstream 1~54

1
[ 68089-73-6 ]
[ 35066-80-9 ]

References: [1]Journal of Organic Chemistry,1957,vol. 22,p. 1243,1245.
[2]Journal of Organic Chemistry,1957,vol. 22,p. 1243,1245.
[3]Tetrahedron,1967,vol. 23,p. 3631 - 3643.
[4]Tetrahedron,1967,vol. 23,p. 3631 - 3643.
[5]Tetrahedron,1967,vol. 23,p. 3631 - 3643.

2
[ 68089-73-6 ]
[ 97692-20-1 ]

References: [1]Angewandte Chemie,1963,vol. 75,p. 418 - 419.

3
[ 68089-73-6 ]
C₁₉H₁₂O^(1-)*K⁽¹⁺⁾ [ No CAS ]

References: [1]Journal of the Chemical Society. Perkin transactions II,1990,p. 513 - 520.

4
[ 68089-73-6 ]
C₁₉H₁₂O^(1-)*Rb⁽¹⁺⁾ [ No CAS ]

References: [1]Journal of the Chemical Society. Perkin transactions II,1990,p. 513 - 520.

5
[ 68089-73-6 ]
C₁₉H₁₂O^(1-)*Cs⁽¹⁺⁾ [ No CAS ]

References: [1]Journal of the Chemical Society. Perkin transactions II,1990,p. 513 - 520.

6
[ 68089-73-6 ]
C₁₉H₁₂O^(1-)*Li⁽¹⁺⁾ [ No CAS ]

References: [1]Journal of the Chemical Society. Perkin transactions II,1990,p. 513 - 520.

7
[ 68089-73-6 ]
C₁₉H₁₂O^(1-)*Na⁽¹⁺⁾ [ No CAS ]

References: [1]Journal of the Chemical Society. Perkin transactions II,1990,p. 513 - 520.

8
[ 68089-73-6 ]
C₁₉H₁₂O^(1-) [ No CAS ]

References: [1]Journal of the Chemical Society. Perkin transactions II,1990,p. 513 - 520.

9
[ 68089-73-6 ]
tribenzo<a.c.e>cycloheptetriene-1-thione [ No CAS ]

References: [1]Journal of Physical Chemistry,1993,vol. 97,p. 8713 - 8717.

10
[ 68089-73-6 ]
[ 591-51-5 ]
[ 95038-29-2 ]

References: [1]Journal of the Chemical Society. Perkin transactions II,1990,p. 2167 - 2177.
[2]Chemische Berichte,1964,vol. 97,p. 1329 - 1336.

11
[ 16567-36-5 ]
[ 68089-73-6 ]

References: [1]Chemische Berichte,1964,vol. 97,p. 1329 - 1336.
[2]Patent: US2019/367491,2019,A1 .

12
[ 68089-73-6 ]
[ 4269-14-1 ]

References: [1]Chemische Berichte,1964,vol. 97,p. 1329 - 1336.

13
[ 13029-09-9 ]
[ 68089-73-6 ]
2,2'-bis(1-hydroxy-2:3,4:5,6:7-tribenzocycloheptatrien-1-yl)biphenyl [ No CAS ]

References: [1]Advanced Synthesis and Catalysis,1996,vol. 338,p. 553 - 557.

14
[ 104-92-7 ]
[ 68089-73-6 ]
9-(4-methoxyphenyl)-9H-tribenzo[a,c,e]cyclohepten-9-ol [ No CAS ]

References: [1]European Journal of Organic Chemistry,2005,p. 2607 - 2619.

15
[ 68089-73-6 ]
4-(tribenzo[a,c,e]cyclohepten-9-ylidene)cyclohexa-2,5-dienone [ No CAS ]

References: [1]European Journal of Organic Chemistry,2005,p. 2607 - 2619.

16
[ 68089-73-6 ]
9-fluorenylidenetribenzocycloheptatriene [ No CAS ]

References: [1]Journal of Physical Chemistry,1993,vol. 97,p. 8713 - 8717.

17
[ 68089-73-6 ]
9-fluorenyltribenzocycloheptatrienethiirane [ No CAS ]

References: [1]Journal of Physical Chemistry,1993,vol. 97,p. 8713 - 8717.

18
[ 68089-73-6 ]
[ 105432-36-8 ]

References: [1]Angewandte Chemie,1963,vol. 75,p. 418 - 419.

19
[ 68089-73-6 ]
[ 15323-16-7 ]

References: [1]Tetrahedron,1967,vol. 23,p. 3631 - 3643.

20
[ 4333-56-6 ]
[ 68089-73-6 ]
[ 23719-80-4 ]
9-cyclopropyl-9H-tribenzo[a,c,e]cyclohepten-9-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With ammonium chloride; magnesium; In tetrahydrofuran;	EXAMPLE 5 (R)-1-(3-(9H-Tribenzo[a,c,e]cyclohepten-9-ylidene)-1-propyl)-3-piperidine-carboxylic acid hydrochloride STR7 A solution of cyclopropylmagnesium bromide in dry tetrahydrofuran (prepared from cyclopropylbromide (4.54 g, 37.5 mmol), magnesium turnings (0.91 g, 37.5 mmol) and dry tetrahydrofuran (30 ml)) was placed under an atmosphere of nitrogen. A solution of 9H-tribenzo[a,c,e]cyclohepten-9-one (1.92 g, 7.5 mmol) (prepared according to W. Tochtermann, Chem. Ber., 97, 1329 (1964)) in tetrahydrofuran (20 ml) was added dropwise and when addition was complete the mixture was heated at reflux temperature for 30 minutes. The reaction mixture was cooled on an ice-bath and saturated ammonium chloride (50 ml) was added carefully. The organic layer was separated and the aqueous phase extracted with diethyl ether (2*100 ml). The combined organic extracts were dried (MgSO4) and the solvent was evaporated in vacuo affording 2.69 g of 9-cyclopropyl-9H-tribenzo[a,c,e]cyclohepten-9-ol.
	With ammonium chloride; magnesium; In tetrahydrofuran;	EXAMPLE 5 (R)-1-(3-(9H-Tribenzo[a,c,e]cyclohepten-9-ylidene)-1-propyl)-3-piperidine-carboxylic acid hydrochloride A solution of cyclopropylmagnesium bromide in dry tetrahydrofuran (prepared from cyclopropylbromide (4.54 g, 37.5 mmol), magnesium turnings (0.91 g, 37.5 mmol) and dry tetrahydrofuran (30 ml)) was placed under an atmosphere of nitrogen. A solution of 9H-tribenzo[a,c,e]cyclohepten-9-one (1.92 g, 7.5 mmol) (prepared according to W. Tochtermann, Chem.Ber., 97, 1329 (1964)) in tetrahydrofuran (20 ml) was added dropwise and when addition was complete the mixture was heated at reflux temperature for 30 minutes. The reaction mixture was cooled on an ice-bath and saturated ammonium chloride (50 ml) was added carefully. The organic layer was separated and the aqueous phase extracted with diethyl ether (2 x 100 ml). The combined organic extracts were dried (MgSO4) and the solvent was evaporated in vacuo affording 2.69 g of 9-cyclopropyl-9H-tribenzo[a,c,e]cyclohepten-9-ol.

References: [1]Patent: US5716949,1998,A .
[2]Patent: EP869954,2001,B1 .

21
[ 68089-73-6 ]
C₂₈H₃₆O₂Si [ No CAS ]
C₁₉H₁₄O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With silica gel; In dichloromethane;	To a stirred solution of diketone 6 (0.50 g, 1.81 mmol) in CH2Cl2 (30mL) at r.t. under argon were added TIPSOTf (0.6 mL, 2.15 mmol) andEt3N (0.25 mL, 2.00 mmol). The mixture was stirred at r.t. for 1.5 h, then filtered through a short pad of silica gel. The filtrate was concentrated under reduced pressure. The crude product was dissolved inCH2Cl2 (20 mL), and treated with DDQ (0.41 g, 1.81 mmol). The mixture was stirred at r.t. for 1.5 h, and then the reaction was quenched with H2O. The mixture was extracted with CH2Cl2, and the extractswere dried (Na2SO4), filtered, and concentrated under reduced pressure(single spot in TLC). The crude product (0.42 g) was purified bytrituration with hexane to give a white solid; yield: 0.26 g (1.03mmol, 57%); mp 177-178 C; Rf = 0.53 (EtOAc-hexane, 1:4).

References: [1]Synthesis,2015,vol. 47,p. 2957 - 2960.

22
[ 84-11-7 ]
[ 68089-73-6 ]

References: [1]Synthesis,2015,vol. 47,p. 2957 - 2960.

23
[ 32260-59-6 ]
[ 68089-73-6 ]

References: [1]Synthesis,2015,vol. 47,p. 2957 - 2960.

24
9-allyl-10-vinyl-9,10-dihydrophenanthrene-9,10-diol [ No CAS ]
[ 68089-73-6 ]

References: [1]Synthesis,2015,vol. 47,p. 2957 - 2960.

25
1-(2'-acryloylbiphenyl-2-yl)but-3-en-1-one [ No CAS ]
[ 68089-73-6 ]

References: [1]Synthesis,2015,vol. 47,p. 2957 - 2960.

26
C₂₈H₃₆O₂Si [ No CAS ]
[ 68089-73-6 ]

Yield	Reaction Conditions	Operation in experiment
57%		To a stirred solution of diketone 6 (0.50 g, 1.81 mmol) in CH2Cl2 (30mL) at r.t. under argon were added TIPSOTf (0.6 mL, 2.15 mmol) andEt3N (0.25 mL, 2.00 mmol). The mixture was stirred at r.t. for 1.5 h, then filtered through a short pad of silica gel. The filtrate was concentrated under reduced pressure. The crude product was dissolved inCH2Cl2 (20 mL), and treated with DDQ (0.41 g, 1.81 mmol). The mixture was stirred at r.t. for 1.5 h, and then the reaction was quenched with H2O. The mixture was extracted with CH2Cl2, and the extractswere dried (Na2SO4), filtered, and concentrated under reduced pressure(single spot in TLC). The crude product (0.42 g) was purified bytrituration with hexane to give a white solid; yield: 0.26 g (1.03mmol, 57%); mp 177-178 C; Rf = 0.53 (EtOAc-hexane, 1:4).

References: [1]Synthesis,2015,vol. 47,p. 2957 - 2960.

27
2-(trifluoromethyl)terphenyl [ No CAS ]
[ 4269-14-1 ]
[ 68089-73-6 ]

References: [1]Chemical Communications,2016,vol. 52,p. 1505 - 1508.

28
[ 68089-73-6 ]
C₁₉H₁₀Br₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
18.9%	With bromine; acetic acid; at 0 - 25℃; for 12h;	In the 250ml three-necked bottle,0.04 mol of tribenzocycloheptene was added,100ml acetic acid stirring dissolved,And then cooled to 0 C with ice salt bath;0.06 mol of Br2 was dissolved in 50 ml of acetic acid,The bromine acetic acid solution was slowly added dropwise to the above reaction system. After completion of the dropwise addition,The temperature of 20-25 C stirring reaction 12 hours;Sampling point plate shows no residual triclocycloheptenone;After completion of the reaction, the reaction solution was neutralized by adding NaOH aqueous solution,Add dichloromethane extraction, stratification, take the organic phase filter, filterThe solution was distilled under reduced pressure to a non-distillate, neutral silicone column,To give intermediate A1, HPLC purity 98.5%, yield 18.9%;

References: [1]Patent: CN106977446,2017,A .Location in patent: Paragraph 0079; 0080.

29
[ 68089-73-6 ]
C₄₃H₂₆N₂O [ No CAS ]