Home Cart Sign in  
Chemical Structure| 149125-30-4 Chemical Structure| 149125-30-4
Chemical Structure| 149125-30-4
Product Citations

Alternative Products

Product Details of [ 149125-30-4 ]

CAS No. :149125-30-4
Formula : C9H4F3NO3
M.W : 231.13
SMILES Code : O=C1NC2=C(C=CC=C2OC(F)(F)F)C1=O
MDL No. :MFCD06804535
InChI Key :JDVUYYNGNVYMKQ-UHFFFAOYSA-N
Pubchem ID :16099928

Safety of [ 149125-30-4 ]

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

Calculated chemistry of [ 149125-30-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 16
Num. arom. heavy atoms 6
Fraction Csp3 0.11
Num. rotatable bonds 2
Num. H-bond acceptors 6.0
Num. H-bond donors 1.0
Molar Refractivity 48.84
TPSA ?

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

55.4 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.26
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

1.9
Log Po/w (WLOGP)?

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

2.41
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.

0.35
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

2.05
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.59

Water Solubility

Log S (ESOL):?

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

-2.62
Solubility 0.56 mg/ml ; 0.00242 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.

-2.69
Solubility 0.476 mg/ml ; 0.00206 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

-3.41
Solubility 0.0895 mg/ml ; 0.000387 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.

-6.36 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

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)

1.92

Application In Synthesis of [ 149125-30-4 ]

* 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 [ 149125-30-4 ]
  • Downstream synthetic route of [ 149125-30-4 ]

[ 149125-30-4 ] Synthesis Path-Upstream   1~2

  • 1
  • [ 848027-63-4 ]
  • [ 149125-30-4 ]
YieldReaction ConditionsOperation in experiment
89% at 60 - 80℃; General procedure: Concentrated sulfuric acid (95 mL) was heated in a flask at 60 C. Intermediates 2 (12 g, 52mmol) were slowly added in portions to maintain the temperature below 70 C. The temperature was then increased to 80 C. After 3 h, the solution was cooled to room temperature, and then poured into crushed ice with vigorous stirring. The precipitate was collected by filtration and dried under vacuum to provide the product 3.
70% at 55 - 80℃; for 0.166667 h; The procedure described by Marvel et al. (see Org. Synth. Coll. Vol. I, 327) was followed. Intermediate 12 (11.9 g, 48.5 mmol) was added in small portions to 35 mL of concentrated sulfuric acid at 55° C. in a 250 mL Erlenmeyer flask. The temperature of the solution was maintained below 70° C. until all the acetamide had been added and it was increased to 80° C. for 10 minutes. The dark-colored solution was cooled to room temperature and poured onto 175 mL of crushed ice. After standing for 30 minutes, the precipitate was collected by filtration, washed three times with water, and dried under vacuum to yield indoline-2,3-dione of sufficient purity to be used in the next step (intermediate 13, 8.32 g, 70percent yield). 1H NMR (400 MHz, DMSO-d6) δ 7.15 (t, J=7.8 Hz, 1H), 7.56 (d, J=7.3 Hz, 1H), 7.64 (d, J=8.3 Hz, 1H), 11.71 (s, 1H).
59%
Stage #1: at 65 - 80℃; for 1.5 h;
Stage #2: With sodium hydroxide In chloroform; water; isopropyl alcohol at 0℃;
According to Scheme 9, concentrated sulfuric acid (40 mL) was heated to 65° C. and poured into a flask containing the crude 2-(trifluoromethoxy)-α-oximinoanilide from Example 1.1. The mixture was stirred at 65° C. until homogeneous and then the temperature was increased to 80° C. After 90 min, the resulting black mixture was poured into ice/water (300 mL) and diluted with 15percent i-PrOH/CHCl3 (200 mL). After slow addition of 6 N NaOH (80 mL, 15 mins), the aqueous layer was extracted with CHCl3 (2.x.80 mL). To the combined organic layers was added silica gel (30 g) and the solvent was then evaporated. The resulting solid was applied to a column of silica gel and eluted with 15-25percent EtOAc/hexanes to provide the product (5.0 g, 59percent, 2 steps): MS(ESI): 230 (M-H)
References: [1] Chinese Chemical Letters, 2017, vol. 28, # 6, p. 1248 - 1251.
[2] Patent: US2008/255192, 2008, A1, . Location in patent: Page/Page column 16-17.
[3] Patent: US2005/59823, 2005, A1, . Location in patent: Page 15.
  • 2
  • [ 1535-75-7 ]
  • [ 149125-30-4 ]
References: [1] Journal of Medicinal Chemistry, 2007, vol. 50, # 1, p. 21 - 39.
[2] Journal of Medicinal Chemistry, 2007, vol. 50, # 1, p. 40 - 64.
[3] Chinese Chemical Letters, 2017, vol. 28, # 6, p. 1248 - 1251.
 

Historical Records

Technical Information

Categories

Related Functional Groups of
[ 149125-30-4 ]

Fluorinated Building Blocks

Chemical Structure| 169037-23-4

A143224 [169037-23-4]

5-(Trifluoromethoxy)indoline-2,3-dione

Similarity: 0.93

Chemical Structure| 343-69-1

A206476 [343-69-1]

6-Trifluoromethylisatin

Similarity: 0.73

Chemical Structure| 345-32-4

A329464 [345-32-4]

5-(Trifluoromethyl)indoline-2,3-dione

Similarity: 0.73

Chemical Structure| 959235-95-1

A126284 [959235-95-1]

6-(Trifluoromethoxy)indoline

Similarity: 0.71

Chemical Structure| 391-12-8

A246178 [391-12-8]

7-(Trifluoromethyl)isatin

Similarity: 0.70

Ethers

Chemical Structure| 169037-23-4

A143224 [169037-23-4]

5-(Trifluoromethoxy)indoline-2,3-dione

Similarity: 0.93

Chemical Structure| 84575-27-9

A145867 [84575-27-9]

7-Methoxyindoline-2,3-dione

Similarity: 0.89

Chemical Structure| 21544-81-0

A715513 [21544-81-0]

4,6-Dimethoxyindoline-2,3-dione

Similarity: 0.78

Chemical Structure| 52351-75-4

A210396 [52351-75-4]

6-Methoxyindoline-2,3-dione

Similarity: 0.75

Chemical Structure| 39755-95-8

A332971 [39755-95-8]

5-Methoxyindoline-2,3-dione

Similarity: 0.75

Amides

Chemical Structure| 169037-23-4

A143224 [169037-23-4]

5-(Trifluoromethoxy)indoline-2,3-dione

Similarity: 0.93

Chemical Structure| 84575-27-9

A145867 [84575-27-9]

7-Methoxyindoline-2,3-dione

Similarity: 0.89

Chemical Structure| 21544-81-0

A715513 [21544-81-0]

4,6-Dimethoxyindoline-2,3-dione

Similarity: 0.78

Chemical Structure| 52351-75-4

A210396 [52351-75-4]

6-Methoxyindoline-2,3-dione

Similarity: 0.75

Chemical Structure| 39755-95-8

A332971 [39755-95-8]

5-Methoxyindoline-2,3-dione

Similarity: 0.75

Ketones

Chemical Structure| 169037-23-4

A143224 [169037-23-4]

5-(Trifluoromethoxy)indoline-2,3-dione

Similarity: 0.93

Chemical Structure| 84575-27-9

A145867 [84575-27-9]

7-Methoxyindoline-2,3-dione

Similarity: 0.89

Chemical Structure| 21544-81-0

A715513 [21544-81-0]

4,6-Dimethoxyindoline-2,3-dione

Similarity: 0.78

Chemical Structure| 52351-75-4

A210396 [52351-75-4]

6-Methoxyindoline-2,3-dione

Similarity: 0.75

Chemical Structure| 39755-95-8

A332971 [39755-95-8]

5-Methoxyindoline-2,3-dione

Similarity: 0.75

Trifluoromethyls

Chemical Structure| 169037-23-4

A143224 [169037-23-4]

5-(Trifluoromethoxy)indoline-2,3-dione

Similarity: 0.93

Chemical Structure| 343-69-1

A206476 [343-69-1]

6-Trifluoromethylisatin

Similarity: 0.73

Chemical Structure| 345-32-4

A329464 [345-32-4]

5-(Trifluoromethyl)indoline-2,3-dione

Similarity: 0.73

Chemical Structure| 959235-95-1

A126284 [959235-95-1]

6-(Trifluoromethoxy)indoline

Similarity: 0.71

Chemical Structure| 391-12-8

A246178 [391-12-8]

7-(Trifluoromethyl)isatin

Similarity: 0.70

Related Parent Nucleus of
[ 149125-30-4 ]

Indolines

Chemical Structure| 169037-23-4

A143224 [169037-23-4]

5-(Trifluoromethoxy)indoline-2,3-dione

Similarity: 0.93

Chemical Structure| 84575-27-9

A145867 [84575-27-9]

7-Methoxyindoline-2,3-dione

Similarity: 0.89

Chemical Structure| 21544-81-0

A715513 [21544-81-0]

4,6-Dimethoxyindoline-2,3-dione

Similarity: 0.78

Chemical Structure| 52351-75-4

A210396 [52351-75-4]

6-Methoxyindoline-2,3-dione

Similarity: 0.75

Chemical Structure| 39755-95-8

A332971 [39755-95-8]

5-Methoxyindoline-2,3-dione

Similarity: 0.75