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Chemical Structure| 230615-59-5 Chemical Structure| 230615-59-5

Structure of 230615-59-5

Chemical Structure| 230615-59-5

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Product Details of [ 230615-59-5 ]

CAS No. :230615-59-5
Formula : C13H10F3N3O5
M.W : 345.23
SMILES Code : FC(F)(F)C(N1CC(C2)C3=CC([N+]([O-])=O)=C([N+]([O-])=O)C=C3C2C1)=O
MDL No. :MFCD10566032
InChI Key :BDTXJBWOCIFUMR-UHFFFAOYSA-N
Pubchem ID :21864744

Safety of [ 230615-59-5 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H315-H319-H228
Precautionary Statements:P240-P210-P241-P264-P280-P302+P352-P370+P378-P337+P313-P305+P351+P338-P362+P364-P332+P313
Class:4.1
UN#:1325
Packing Group:

Computational Chemistry of [ 230615-59-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 24
Num. arom. heavy atoms 6
Fraction Csp3 0.46
Num. rotatable bonds 4
Num. H-bond acceptors 8.0
Num. H-bond donors 0.0
Molar Refractivity 81.03
TPSA ?

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

111.95 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.52
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

2.2
Log Po/w (WLOGP)?

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

3.36
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.

0.7
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

-1.51
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.25

Water Solubility

Log S (ESOL):?

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

-3.29
Solubility 0.178 mg/ml ; 0.000516 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.

-4.19
Solubility 0.0225 mg/ml ; 0.0000653 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

-2.21
Solubility 2.11 mg/ml ; 0.00612 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

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

Yes
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.

-6.84 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

0.0
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

2.0 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<0.0
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)

3.15

Application In Synthesis of [ 230615-59-5 ]

* 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.

  • Downstream synthetic route of [ 230615-59-5 ]

[ 230615-59-5 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 230615-51-7 ]
  • 3-(trifluoroacetyl)-6,8-dinitro-2,3,4,5-tetrahydro-1H-1,5-methano-3-benzazepine [ No CAS ]
  • [ 230615-59-5 ]
YieldReaction ConditionsOperation in experiment
With trifluorormethanesulfonic acid; nitric acid; In dichloromethane; at 0 - 15℃;Product distribution / selectivity; On the other hand, a 500 mL round bottom flask with thermometer, condenser, addition funnel and magnetic stirring was charged with CF3SO3H (25.9 g, 172.5 mmol), CH2Cl2 (110 mL) and cooled to 0-5 0C. At this temperature, fuming nitric acid (5.4 g, 86.25 mmol) was added slowly. To the resulting slurry at 0-5 0C, the solution obtained in the previous step was slowly added, maintaining the temperature < 15 0C. After the addition, the reaction mixture was stirred overnight. The complete dinitration was confirmed by GC. The crude reaction mixture was poured into water (60 mL) an ice (80 g) and stirred. The phases were separated and the aqueous phase was extracted with CH2Cl2 (3 x 50 mL) . The mixture of the organic phases was washed with aqueous saturated NaHCO3, dried over Na2SO4 and volatiles evaporated under vacuum to obtain 11.9 g of a solid that was suspended and stirred for 2 hours in AcOEt (12 mL) and hexanes (24 mL) . The solid was filtered and washed with hexanes to <n="13"/>obtain the compound of formula (III), 9.1g with a purity of 88.9% by GC (9.8% of meta-dimtrocompound impurity) .
  • 2
  • [ 230615-51-7 ]
  • [ 230615-59-5 ]
YieldReaction ConditionsOperation in experiment
68.9% With trifluorormethanesulfonic acid; nitric acid; In dichloromethane; at 0 - 30℃;Product distribution / selectivity; Example 10Procedure for Preparation of 1-(4,5-Dinitro-10-aza-tricyclo[6.3.1.02,7]dodeca-2(7),3,5-triene-10-yl)-2,2,2-trifluoro-ethanone (IX); Fuming nitric acid (390.2 g) was added over 25 to 35 minutes at 0 to 5 C. to a solution of tri-fluoro methane sulfonic acid (1.7 kg) in MDC (2.52 l). The mixture was stirred for 10-15 minutes. To this resulting organic layer, <strong>[230615-51-7]1-(10-Aza-tricyclo[6.3.1.02,7]dodeca-2(7),3,5-triene-10-yl)-2,2,2-trifluoro-ethanone</strong> in MDC was added over 1.0 to 1.5 hours at 0 to 5 C. After completion of addition, the temperature was immediately raised to 25 to 30 C. The reaction mass was stirred at 25 to 30 C. for 2.0 hours. The progress of the reaction was checked by HPLC. The reaction mixture was quenched in DM water (6.5 l) at 0 to 5 C. The layers were separated, and the aqueous layer was extracted with MDC (2×1.26 l). The combined organic layer was washed with DM water (3×3.2 l), and then with an 8 percent aqueous NaHCO3 solution (1×3.2 l) and DM water (1×2.5 l). The organic layer was concentrated to provide crude 1-(4,5-Dinitro-10-aza-tricyclo[6.3.1.02,7]dodeca-2(7),3,5-triene-10-yl)-2,2,2-trifluoro-ethanone. This was triturated with ethyl acetate (1.30 l) at 55 to 60 C. for 2 hours. The solid was filtered and washed with chilled ethyl acetate (630 ml) to provide pure 1-(4,5-Dinitro-10-aza-tricyclo[6.3.1.02,7]dodeca-2(7),3,5-triene-10-yl)-2,2,2-trifluoro-ethanone having a yield of 68.9 percent and an HPLC purity of 99.55 percent.
With trifluorormethanesulfonic acid; nitric acid; In dichloromethane; at 0 - 15℃;Product distribution / selectivity; A l L round bottom flask with thermometer, condenser, addition funnel and magnetic stirring was charged with CF3SO3H (67.8 g, 452 mmol), CH2Cl2 (280 mL) and cooled to 0-5 0C. At this temperature, fuming nitric acid (14.2 g, 226 mmol) was slowly added. To the resulting slurry at 0-5 0C, the solution obtained in the previous step was slowly added, maintaining the temperature < 15 0C. After the addition, the reaction mixture was stirred overnight. The complete dinitration was confirmed by GC. The crude reaction mixture was poured into water (150 mL) an ice (200 g) and stirred. The phases were separated and the aqueous phase was extracted with CH2Cl2 (100 mL) . The mixture of the organic phases was washed with aqueous saturated NaHCO3 <n="18"/>(2x100 mL) , water (100 mL) , dried over Na2SO4 and volatiles evaporated under vacuum to obtain 30.5 g of a solid with a 83.6% purity by GC (12.5% of meta- dinitrocompound impurity) . 20 g of this solid were crystallized in toluene (100 mL) to obtain the compound of formula (III), 15 g of a pale brown solid with a 98.5 % purity by GC (meta-dinitrocompound impurity not detected) .
With sulfuric acid; nitric acid; In dichloromethane; at 0 - 30℃; for 7.0h; Fuming nitric acid (39 g) was slowly added to a solution concentrated sulfuric acid (126.17 g) in methylene chloride (450 ml) followed by stirring at O0C to generate a white precipitate. This step was followed by drop wise addition of a solution of l-(10-aza- tricyclo[6.3.1.02 7]dodeca-2(7),3,5-trien-10-yl)-2,2,2-trifluoro-ethanone (65 g) in methylene chloride (100 ml) through an addition funnel over 30 minutes. The reaction mixture was stirred for 2 hours 30 minutes at 00C and then stirred for 4 hours at 25-30C. The resulting mass was poured into a vigorously stirred mixture of water (650 ml) at 15-200C. The resulting layers were separated and the aqueous layer was extracted with methylene chloride (I x 325 ml). The organic layers were combined and washed with water (3 x 650 ml) and then dried over sodium sulfate and concentrated to afford a solid. The resulting solid was slurried with methanol (325 ml), filtered and dried to yield 60 g of l-(4,5-dinitro-10-aza- tricyclo[6.3.1.02 7]dodeca-2(7),3,5-trien-10-yl)-2,2,2-trifluoro-ethanone as off-white solid (Purity by HPLC: 99.5%).
 

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Technical Information

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