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Structure of 1300750-50-8

Chemical Structure| 1300750-50-8

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Product Details of [ 1300750-50-8 ]

CAS No. :1300750-50-8
Formula : C6H6BF2NO3
M.W : 188.92
SMILES Code : FC(F)OC1=NC=CC=C1B(O)O
MDL No. :MFCD18261901
InChI Key :YTNMJXVIJXDALS-UHFFFAOYSA-N
Pubchem ID :71302322

Safety of [ 1300750-50-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 1300750-50-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 6
Fraction Csp3 0.17
Num. rotatable bonds 3
Num. H-bond acceptors 6.0
Num. H-bond donors 2.0
Molar Refractivity 40.66
TPSA ?

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

62.58 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.0
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

1.01
Log Po/w (WLOGP)?

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

0.2
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.

-0.84
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

-0.73
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.07

Water Solubility

Log S (ESOL):?

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

-1.79
Solubility 3.06 mg/ml ; 0.0162 mol/l
Class?

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

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-1.91
Solubility 2.31 mg/ml ; 0.0122 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

-1.26
Solubility 10.3 mg/ml ; 0.0543 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

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.

-6.74 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

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)

2.32

Application In Synthesis of [ 1300750-50-8 ]

* 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 [ 1300750-50-8 ]

[ 1300750-50-8 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 1300750-50-8 ]
  • [ 24358-62-1 ]
  • (R)-1-[4-(2-difluoromethoxy-pyridin-3-yl)-phenyl]-ethylamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With palladium diacetate; In water; at 200.0℃; for 0.08333330000000001h;Microwave irradiation; General procedure: Palladium acetate (56 mg, 0.25 mmol) was added to a mixture of 5-fluoro-2-methoxyphenylboronic acid (850 mg, 5.0 mmol) and (R)-1-(4-bromophenyl)ethylamine (500 mg, 2.5 mmol) in water (20 ml). This mixture was heated for 5 min at 200 C in a Smithcreator microwave oven and then diluted with methanol (200 ml). The mixture was purified on a SCX column (20 g)using 2 M ammonia in methanol to elute the intermediate amine. Evaporation of solvents under reduced pressure gave (R)-1-(50-fluoro-2'-methoxybiphenyl-4-yl)-ethylamine as a gum (580 mg, 2.37 mmol, 96.6%).Triethylamine (41.1 ll, 0.295 mmol) and 1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-sulfonyl chloride (24.5 mg, 0.0984 mmol) were added to a solution of (R)-1-(5'-fluoro-2'-methoxy-biphenyl-4-yl)-ethylamine (20 mg,0.082 mmol) in dichloromethane (1 ml) and the resulting solution shaken at room temperature overnight. Purification by preparative LCMS and removal of solvent under reduced pressure gave 19 (8.5 mg, 40%):
  • 2
  • [ 1300750-50-8 ]
  • 5-bromo-1-isopropyl-N-((2-methoxypyridin-3-yl)methyl)-3-methyl-1H-pyrazolo[4,3-b]pyridin-7-amine [ No CAS ]
  • 5-[2-(difluoromethoxy)-3-pyridyl]-1-isopropyl-N-[(2-methoxy-3-pyridyl)methyl]-3-methyl-pyrazolo[4,3-b]pyridin-7-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100.0℃; for 0.5h;Microwave irradiation; To a solution of 5-chloro-1-isopropyl-3-methyl-N-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-1H-pyrazolo[4,3-b]pyridin-7-amine (50 mg, 70 muetaiotaomicronIota) and (2-ethoxypyridin-3-yl)boronic acid (21 mg, 0.13 mmol) in dioxane (2 ml_) and H20 (0.7 ml_) was added Cs2C03(57 mg, 175 muetaiotaomicronIota) and Pd(1 ,1 '-bis(diphenylphosphino)ferrocene)Cl2(10 mg, 14 muetaiotaomicronIota). The mixture was purged with nitrogen for 3 minutes then stirred at 100C for 30 minutes under microwave irradiation. Water (30 ml_) was added and the mixture was extracted with ethyl acetate (30 ml_chi3). The combined organic layers were washed with brine (20 ml_), dried over Na2S04and concentrated. The crude mixture was purified by preparative TLC with dichloromethane: methanol = 20:1 twice, and then the crude product was further purified by preparative HPLC to 5-(2-ethoxy-3-pyridyl)-1-isopropyl-3-methyl-N-[(5-methyl-1,3,4-oxadiazol-2-yl)methyl]pyrazolo[4,3-b]pyridin-7-amine (6.1 mg). 1H NMR (chloroform-d, 400 MHz) delta 8.28-8.26 (m, 1 H), 8.19-8.18 (m, 1 H), 7.23 (s, 1 H), 7.05- 7.02 (m, 1 H), 5.27 (brs, 1 H), 4.96-4.90 (m, 1 H), 4.71 (d, J = 1 .2 Hz, 2H), 4.53-4.48 (m, 2H), 2.65 (s, 3H), 2.57 (s, 3H), 1.66 (d, J = 6.4 Hz, 6H), 1 .43 (t, J = 6.8 Hz, 3H). LC-MS (m/z) 408.2 (MH+); tR= 2.08 minutes (Method B).
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100.0℃; for 0.55h;Inert atmosphere; Microwave irradiation; General procedure: To a solution of 5-chloro-l-isopropyl-3-methyl-//-((5-methyl-l,3,4-oxadiazol-2-yl)methyl)-l/-/- pyrazolo[4,3-b]pyridin-7-amine (50 mg, 70 pmol) and (2-ethoxypyridin-3-yl)boronic acid (21 mg, 0.13 mmol) in dioxane (2 mL) and H2O (0.7 mL) was added CS2CO3 (57 mg, 175 pmol) and Pd(l,l'- bis(diphenylphosphino)ferrocene)Cl2 (10 mg, 14 pmol). The mixture was purged with nitrogen for 3 minutes then stirred at 100C for 30 minutes under microwave irradiation. Water (30 mL) was added and the mixture was extracted with ethyl acetate (30 mL c 3). The combined organic layers were washed with brine (20 mL), dried over Na2S04 and concentrated. The crude mixture was purified by preparative TLC with dichloromethane: methanol = 20:1 twice, and then the crude product was further purified by preparative HPLC to give 5-(2-ethoxypyridin-3-yl)-l-isopropyl-3-methyl-//-((5- methyl-l,3,4-oxadiazol-2-yl)methyl)-l/-/-pyrazolo[4,3-b]pyridin-7-amine (6.1 mg). XH NMR (chloroform-d, 400 MHz) d 8.28-8.26 (m, 1H), 8.19-8.18 (m, 1H), 7.23 (s, 1H), 7.05-7.02 (m, 1H), 5.27 (brs, 1H), 4.96-4.90 (m, 1H), 4.71 (d, J = 1.2 Hz, 2H), 4.53-4.48 (m, 2H), 2.65 (s, 3H), 2.57 (s, 3H), 1.66 (d, J = 6.4 Hz, 6H), 1.43 (t, J = 6.8 Hz, 3H). LC-MS (m/z) 408.2 (MH+); tR = 2.08 minutes (Method B).
 

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