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Chemical Structure| 1260383-51-4 Chemical Structure| 1260383-51-4
Chemical Structure| 1260383-51-4

*Storage: Sealed in dry,Room Temperature.

4-Fluoro-2-methyl-1H-indole

CAS No.: 1260383-51-4

4.5 *For Research Use Only !

Cat. No.: A709984 Purity: 95%

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Product Details of [ 1260383-51-4 ]

CAS No. :1260383-51-4
Formula : C9H8FN
M.W : 149.17
SMILES Code : CC(N1)=CC2=C1C=CC=C2F
MDL No. :MFCD18380834
InChI Key :PHGHGDMLJZDQIR-UHFFFAOYSA-N
Pubchem ID :22490033

Safety of [ 1260383-51-4 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H320-H335
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338

Calculated chemistry of [ 1260383-51-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 9
Fraction Csp3 0.11
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 43.22
TPSA ?

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

15.79 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.85
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

2.68
Log Po/w (WLOGP)?

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

3.04
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.

2.31
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

3.41
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.66

Water Solubility

Log S (ESOL):?

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

-3.06
Solubility 0.13 mg/ml ; 0.000874 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.

-2.66
Solubility 0.323 mg/ml ; 0.00217 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

-3.93
Solubility 0.0175 mg/ml ; 0.000117 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.

-5.31 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)

1.68

Application In Synthesis [ 1260383-51-4 ]

* 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.

  • Downstream synthetic route of [ 1260383-51-4 ]

[ 1260383-51-4 ] Synthesis Path-Downstream   1~20

  • 2
  • [ 1260383-51-4 ]
  • [ 1354699-89-0 ]
  • 3
  • [ 1260383-51-4 ]
  • [ 1354699-93-6 ]
  • 4
  • [ 1260383-51-4 ]
  • [ 1354699-94-7 ]
  • 5
  • [ 1260383-51-4 ]
  • [ 4330-21-6 ]
  • [ 1354699-92-5 ]
  • 7
  • [ 443-86-7 ]
  • [ 1260383-51-4 ]
  • 8
  • [ 129822-38-4 ]
  • [ 1260383-51-4 ]
  • 9
  • [ 1383976-61-1 ]
  • [ 1260383-51-4 ]
YieldReaction ConditionsOperation in experiment
0.19 g With trifluoroacetic acid; In dichloromethane; at 20℃; for 24h; Step 3a4-Fluoro-2-methylindole 1.43 ml of trifluoroacetic acid are added to a solution of 0.35 g of tert-butyl [3-fluoro-2-(2-oxopropyl)phenyl]carbamate in 13 ml of anhydrous dichloromethane at ambient temperature. The reaction mixture is then stirred at ambient temperature for 24 h, and is then diluted with 27 ml of dichloromethane and treated with 25 ml of a 5% sodium hydrogen carbonate solution. After stirring at ambient temperature for 1 hour and then settling out, the organic phase is separated and the aqueous phase is extracted with 25 ml of dichloromethane. The organic phases are combined, washed with saturated brine, dried over magnesium sulfate, filtered, and then concentrated to dryness under reduced pressure. 0.19 g of 4-fluoro-2-methylindole is thus obtained in the form of a dark red-colored oil, the characteristics of which are the following:1H NMR spectrum (400 MHz, CDCl3): 2.46 (s, 3H); 6.30 (broad m, 1H); 6.74 (dd, J=7.9 and 10.6 Hz, 1H); 7.02 (dt, J=4.9 and 7.9 Hz, 1H); 7.08 (d, J=7.9 Hz, 1H); 7.95 (broad m, 1H)Mass spectrometry: EI: [M]+. m/z=149
  • 10
  • [ 1260383-51-4 ]
  • [ 1383976-62-2 ]
YieldReaction ConditionsOperation in experiment
2.19 g With sodium cyanoborohydride; acetic acid; at 14 - 20℃; for 2h;Inert atmosphere; Step 4a4-Fluoro-2-methyl-2,3-dihydro-1H-indole 3.63 g of sodium cyanoborohydride are gradually added to a solution of 2.87 g of <strong>[1260383-51-4]4-fluoro-2-methylindole</strong> in 98 ml of acetic acid under argon cooled to a temperature of about 14 C. The reaction mixture is left to warm up to ambient temperature. After 2 hours, the reaction mixture is poured into a mixture of water and ice, and is then treated with a 28% aqueous ammonia solution until the pH is 9. The mixture is then extracted twice with dichloromethane. The organic phases are combined, dried over anhydrous magnesium sulfate, filtered, and then concentrated to dryness under reduced pressure. The residue is purified on a 300 g silica column, elution being carried out with a 100/0 to 90/10 v/v heptane/ethyl acetate gradient. 2.19 g of 4-fluoro-2-methyl-2,3-dihydro-1H-indole are thus obtained in the form of a colorless oil, the characteristics of which are the following:1H NMR spectrum (400 MHz): 1.18 (d, J=6.3 Hz, 3H); 2.49 (partially masked dd, J=7.6 and 15.7 Hz, 1H); 3.08 (dd, J=9.0 and 15.7 Hz, 1H); 3.92 (m, 1H); 5.87 (broad s, 1H); 6.20 to 6.31 (m, 2H); 6.90 (td, J=5.9 and 8.1 Hz, 1H)Mass spectrometry: method ARetention time Tr (min)=0.50;[M+H]+: m/z 152
  • 11
  • [ 1260383-51-4 ]
  • (R)-2-benzyloxy-1-(4-fluoro-2-methyl-2,3-dihydroindol-1-yl)propan-1-one [ No CAS ]
  • 12
  • [ 1260383-51-4 ]
  • (+)-4-fluoro-2-methyl-2,3-dihydro-1H-indole [ No CAS ]
  • 13
  • [ 1260383-51-4 ]
  • (-)-4-fluoro-2-methyl-2,3-dihydro-1H-indole [ No CAS ]
  • 14
  • [ 1260383-51-4 ]
  • (-)-2-{2-[4-fluoro-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-3-methyl-6-(morpholin-4-yl)pyrimidin-4(3H)-one [ No CAS ]
  • 15
  • [ 1260383-51-4 ]
  • [ 1542711-17-0 ]
  • C28H30FN5O2 [ No CAS ]
  • 16
  • [ 1260383-51-4 ]
  • [ 1542711-17-0 ]
  • [ 1542705-08-7 ]
  • 17
  • [ 387-43-9 ]
  • [ 1260383-51-4 ]
  • 18
  • C11H14FNO2 [ No CAS ]
  • [ 1260383-51-4 ]
YieldReaction ConditionsOperation in experiment
42.6% With hydrogenchloride; In methanol; water; for 3h;Inert atmosphere; Reflux; 1L reaction flask equipped with mechanical stirring, a condenser and a thermometer, under nitrogen atmosphere was added 53g indole reduction, 28g hydrochloric acid, 500mL methanol, 40mL water, warmed to reflux, incubated 3h. The mixture was concentrated under reduced pressure to dryness. 200 mL of water and 150 mL of ethyl acetate were extracted twice. The combined ethyl acetate layers were washed with water, dried and concentrated to dryness to give 34 g of an oily liquid. Purity: 99.8%, molar yield: 42.6%.
  • 19
  • [ 6921-22-8 ]
  • [ 1260383-51-4 ]
  • 20
  • C9H8FNO3 [ No CAS ]
  • [ 1260383-51-4 ]
 

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