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Chemical Structure| 866319-00-8

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Product Details of [ 866319-00-8 ]

CAS No. :866319-00-8
Formula : C7H5FN2
M.W : 136.13
SMILES Code : FC1=CN=C2C(=C1)C=C[NH]2
MDL No. :MFCD06659678
InChI Key :BALBNSFYMXBWNM-UHFFFAOYSA-N
Pubchem ID :20784462

Safety of [ 866319-00-8 ]

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

Computational Chemistry of [ 866319-00-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 9
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 36.05
TPSA ?

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

28.68 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.43
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

1.41
Log Po/w (WLOGP)?

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

2.12
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.

1.42
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

2.5
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.77

Water Solubility

Log S (ESOL):?

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

-2.24
Solubility 0.786 mg/ml ; 0.00578 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.

-1.62
Solubility 3.29 mg/ml ; 0.0242 mol/l
Class?

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

Very 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

-3.16
Solubility 0.0944 mg/ml ; 0.000693 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.

-6.13 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

1.0
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)

1.55

Application In Synthesis of [ 866319-00-8 ]

* 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 [ 866319-00-8 ]

[ 866319-00-8 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 866319-00-8 ]
  • [ 1190321-96-0 ]
  • 2
  • [ 866319-00-8 ]
  • [ 1190309-71-7 ]
YieldReaction ConditionsOperation in experiment
81.56% With N-Bromosuccinimide; In N,N-dimethyl-formamide; at -10℃; for 1h; At -10 C., to a solution of the compound BB-3-4 (7.40 g, 54.36 mmol) in DMF (100.00 mL) was added N-bromo-succinimide (9.67 g, 54.36 mmol). The mixture was stirred at -10 C. for one hour. Water (100 mL) was added dropwise into the reaction liquid, the mixture was filtered, and the soiled was spun to dry to give the compound BB-3-5 (11.50 g, 44.34 mmol, yield 81.56%). MS (ESI) m/z=217.0 [M+1].
64% With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 0℃; for 2h; To a stirred solution of 5-fluoro-1H-pyrrolo[2,3-b]pyridine (4.5 g, 33 mmol) in DMF (50 mL) was added NBS (6.4 g, 36 mmol) in portions at 0 C and left it for 2 h. After completion of the reaction as indicated by TLC, the reaction mixture was poured into ice cold water (100 mL), filtered the precipitated solid and dried under vacuum to afford 3-bromo-5-fluoro-1H-pyrrolo[2,3-b]pyridine (5) (4.6 g, 21 mmol, 64%) as pale brown solid. TLC system: 20% EtOAc in hexanes Rf : 0.5 LCMS (ESI): m/z 215 [M+H]+.
64% With N-Bromosuccinimide; In N,N-dimethyl-d6-formamide; at 0℃; for 2h; To a stirred solution of 5-fluoro-1H-pyrrolo[2,3-b]pyridine (4.5 g, 33 mmol) in DMF (50 mL) was added NBS (6.4 g, 36 mmol) in portions at 0 C and left it for 2 h. After completion of the reaction as indicated by TLC, the reaction mixture was poured into ice cold water (100 mL), filtered the precipitated solid and dried under vacuum to afford 3-bromo-5- fluoro-1H-pyrrolo[2,3-b]pyridine (5) (4.6 g, 21 mmol, 64%) as pale brown solid. TLC system: 20% EtOAc in hexanes Rf : 0.5 LCMS (ESI): m/z 215 [M+H]+
40% With bromine; In N,N-dimethyl-formamide; at 20℃; for 4h; To the solution of 5-fluoro-1H-pyrrolo[2,3-b]pyridine (1 g, 7.34 mmol) in DMF (10 mL) was added bromine (0.75 mL, 14.5 mmol). The mixture was stirred at it for 4 hours. The reaction mixture was quenched with saturated aqueous sodium thiosulfate (100 mL). The resulting mixture was extracted with ethyl acetate (100 mL x 2). The combined organic layers were washed with saturated brine (100 mL x 3), dried over ahydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo, and the residue was purified by silica gel column chromatography (PE/EtOAc (v/v) = 4/1) to give the title compound as yellow powder (0.6 g, 40%).MS (ESI, pos. ion) m/z: 216.9 [M+H]+1H NMR (400 MHz, DMSO-d6) ö (ppm): 12.23 (s, 1H), 8.35-8.21 (m, 1H), 7.81 (d, J = 2.7 Hz, 1H), 7.71 (dd, J = 8.9, 2.6 Hz, 1H).
40% With bromine; In N,N-dimethyl-formamide; at 20℃; for 4h; To a solution of 5-fluoro-1H-pyrrolo[2,3-b]pyridine (1.0 g, 7.34 mmol) in DMF (10 mL) was added bromine (0.75 mL, 14.5 mmol) . The reaction mixture was stirred at r. t. for 4 h. A saturated aqueous Na2S2O3 solution (100 mL) was added to quench the reaction, and the resulting mixture was extracted with EtOAc (100 mL × 2) . The combined organic phases were washed with saturated brine (100 mL × 3) , dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated in vacuo. The residue was purified by silica gel chromatograph (PE/EtOAc (v/v) 4/1) to give the tilte compound as a yellow solid (0.6 g, 40 %). MS (ESI, pos. ion) m/z: 216.9 [M+H]+ 1H NMR (400 MHz, DMSO-d6) δ (ppm) : 12.23 (s, 1H) , 8.35-8.21 (m, 1H) , 7.81 (d, J 2.7 Hz, 1H) , 7.71 (dd, J 8.9, 2.6 Hz, 1H).
40% With bromine; at 20℃; for 4h; 5-Fluoro-1H-pyrrolo[2,3-b]pyridine (1 g, 7.34 mmol) was dissolved in DMF (10 mL)Then, bromine (0.75 mL, 14.5 mmol) was added dropwise thereto, and the reaction was stirred at room temperature for 4 hours.Quenched with saturated aqueous sodium thiosulfate solution (100 mL)The reaction mixture was extracted with ethyl acetate (100 mL×2).The combined organic phases were washed with brine (100 mL×3)Filtered, concentrated under reduced pressure,The residue was subjected to silica gel column chromatography(PE/EtOAc (v/v) = 4/1) purified,The title compound was obtained as a yellow powder (0.6 g, 40%).
40% With bromine; In N,N-dimethyl-formamide; at 20℃; for 4h; 5-Fluoro-1H-pyrrolo[2,3-b]pyridine (1 g, 7.34 mmol) was dissolved in DMF (10 mL)Then bromine (0.75 mL, 14.5 mmol) was added dropwise thereto.The reaction was stirred at room temperature for 4 hours.The reaction was quenched by the addition of saturated aqueous sodium thiosulfate (100 mL).The resulting mixture was extracted with ethyl acetate (100 mL X 2).The combined organic phases were washed with saturated brine (100 mL×3).Dry over anhydrous sodium sulfate, filter,Concentrated under reduced pressure, and the residue was applied to silica gel column chromatography(Petroleum ether / ethyl acetate (ν / ν) = 4 / 1) purification,The title compound was obtained as a yellow powder (0.6 g, 40%).
With N-Bromosuccinimide; In dichloromethane; at 20℃; for 19h; Preparation of compound 2: N-bromosuccinimide (NBS, 5 · 29 g, 29 · 7 mmol) was added to a solution of compound 1 (4.50 g, 33 mmol) in dichloromethane (100 mL) and react at room temperature 19 hour,After the reaction, a saturated sodium hydrogen sulfite solution (200 ml) was added, and the mixture was separated.The organic layer was washed with 20% sodium hydroxide solution.Dry over anhydrous sodium sulfate, filter,The filtrate was concentrated in vacuo to give a crude product4.62g.
With N-Bromosuccinimide; In dichloromethane; at 20℃; for 19h; N-bromosuccinimide (NBS, 5.29 g, 29.7 mmol) was added to Compound 6(4.50 g, 33 mmol) in dichloromethane (100 mL) and reacted at room temperature for 19 hours,After the reaction was completed, a saturated sodium bisulfite solution (200 mL) was added.The layers were separated, and the organic layer was washed with 20% sodium hydroxide solution and dried over anhydrous sodium sulfate.Filtration and concentration of the filtrate in vacuo gave the crude product4.62g.

 

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