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Structure of 144100-07-2

Chemical Structure| 144100-07-2

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Product Details of [ 144100-07-2 ]

CAS No. :144100-07-2
Formula : C5H3BrFN
M.W : 175.99
SMILES Code : C1=CC=C(F)N=C1Br
MDL No. :MFCD03095258
InChI Key :ZIDIKYIZXMYHAW-UHFFFAOYSA-N
Pubchem ID :639438

Safety of [ 144100-07-2 ]

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

Computational Chemistry of [ 144100-07-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 31.9
TPSA ?

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

12.89 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.75
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

1.76
Log Po/w (WLOGP)?

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

2.4
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.

1.68
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

2.54
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.03

Water Solubility

Log S (ESOL):?

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

-2.59
Solubility 0.447 mg/ml ; 0.00254 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.

-1.65
Solubility 3.96 mg/ml ; 0.0225 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

-3.15
Solubility 0.124 mg/ml ; 0.000703 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.

-6.12 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

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)

1.9

Application In Synthesis of [ 144100-07-2 ]

* 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 [ 144100-07-2 ]

[ 144100-07-2 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 144100-07-2 ]
  • [ 73183-34-3 ]
  • [ 842136-58-7 ]
YieldReaction ConditionsOperation in experiment
76% With (dppf)2PdCl2.HCl; potassium acetate; In 1,4-dioxane; at 20 - 115℃; for 1h;Inert atmosphere; 2-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine Pd(dppf)2Cl2.HCl (102 mg, 0.14 mmol) was added to a degassed mixture of 2-bromo-6-fluoropyridine (410 mg, 2.33 mmol), bis(pinacolato)diboron (828 mg, 3.26 mmol) and KOAc (685 mg, 6.99 mmol) in dioxane (6 mL) at room temperature. The mixture was heated at 115 C. for 1 h. The solid material was then filtered off the solvent evaporated and the crude compound purified by chromatography (silica, MeOH in DCM 0:100 to 10:90). The desired fractions were collected to obtain the title compound (400 mg, 76%). 1H NMR (400 MHz, CDCl3) 7.78 (td, J=8.1, 7.2 Hz, 1H), 7.70 (ddd, J=6.9, 2.8, 0.9 Hz, 1H), 6.98 (ddd, J=8.1, 2.7, 0.9 Hz, 1H), 1.38 (s, 12H),
With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In dimethyl sulfoxide; at 80℃; for 3h; 2-Fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine 2-bromo-6-fluoropyridine (200 mg, 1.136 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi-1,3,2-dioxaborolane (317 mg, 1.250 mmol), potassium acetate (335 mg, 3.41 mmol), PdCl2(dppf) (83 mg, 0.114 mmol) were collected in a vial, deareated, and then suspended in DMSO (10 ml) under nitrogen atmosphere. The resulting mixture was stirred at 80 C. for 3 hours, diluted with DCM (500 ml) and washed with water (5*100 ml). The resulting organic phase was concentrated under vacuum to give 250 mg of a crude residue which was used in the next step without any further purification. UPLC-MS: 0.38 min, 142 [M-C6H10+H]+
With potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; at 100℃; for 18h; A mixture of 2-bromo-6-fluoropyridine (1.056 g, 6 mmol), 4, 4, 4', 4', 5, 5,5', 5'- octamethyl-2,2'-bi(1 ,3,2-dioxaborolane) (1.60 g, 6.30 mmol), PdCI2(dppf) CH2CI2 adduct (0.294 g, 0.360 mmol) and potassium acetate (1.767 g, 18.00 mmol) in dioxane (12 mL) was stirred at 100 C for 18 hrs. The reaction mixture was cooled to room temperature, diluted with EtOAc (40 mL), filtered and concentrated under reduced pressure. The crude material of 2-fluoro-6-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)pyridine was directly used in the next step without further purification. LCMS (m/z): 142.0 [MS fragment]; Rt = 0.35 min. [Note: LCMS shows only boronic acid fragment.]
With Nonafluorobutanesulfonyl fluoride;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; at 100℃; for 18h; A mixture of 2-bromo-6-fluoropyridine (1 .056 g, 6 mmol), 4, 4, 4', 4', 5, 5,5', 5'- octamethyl-2,2'-bi(1 ,3,2-dioxaborolane) (1 .60 g, 6.30 mmol), PdCI2(dppf) CH2CI2 adduct(0.294 g, 0.360 mmol) and potassium acetate (1 .767 g, 18.00 mmol) in dioxane (12 mL) was stirred at 100 C for 18 hrs. The reaction mixture was cooled to room temperature, diluted with EtOAc (40 mL), filtered and concentrated under reduced pressure. The crude material of 2-fluoro-6-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)pyridine was directly used in the next step without further purification. LCMS (m/z): 142.0 [MS fragment]; Rt = 0.35 min. [Note: LCMS shows only boronic acid fragment.]
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 110℃; for 10h;Inert atmosphere; To a solution of 2-bromo-6-fluoropyridine (5.0 g, 28.4 mmol) in 1,4-dioxane (150 mL) was added 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(l,3,2-dioxaborolane) (8.6 g, 34.1 mmol), and potassium acetate (5.6 g, 56.8 mmol) followed by [l,l '-bis(diphenylphosphino)ferrocene] dichloropalladium(II) (1.2 g, 1.4 mmol) and the mixture was degassed with nitrogen. The mixture was heated at 1 10C for 10 hours, diluted with ethyl acetate and filtered through diatomaceous earth. The filtrate was concentrated and purified by column chromatography (silica gel, 20% ethyl acetate in hexane) to afford the title compound. LCMS: 224 (M+H)+.
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 80℃;Inert atmosphere; To a solution of 2-bromo-6-fluoropyridine (5.32 g,30.23 mmol), potassium acetate (9.02 g, 90.70 mmol) andbis(pinacolato)diboron(8.11 g, 31.75 mmol) in 1,4-dioxane was added[1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex withdichloromethane (1:1) (7.89 g, 1.81 mmol), followed by stirring at 80Covernight under a nitrogen atmosphere. After cooling, the reaction mixture wasdiluted with ethyl acetate (40 mL), then filtered through pad of Celite. Thefiltrate was concentrated under reduced pressure to afford 25.65 g of 2-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine,which was used directly without further purification. To a solution of thiscrude compound (7.08 g), compound 7 (4.00g, 8.34 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium (II),complex with dichloromethane (1:1) (0.72 g, 0.88 mmol) in 1,2-dimethoxyethane(80 mL) was added sodium bicarbonate (2.0 M in water, 22.5 mL, 45.0 mmol),followed by stirring at 95C for 1 hour under a nitrogen atmosphere. Aftercooling, the mixture was diluted with chloroform, and washed with saturatedaqueous brine solution. The organic layer was dried over anhydrous sodium sulfateand concentrated under reduced pressure. The residue was purified by flashcolumn chromatography on silica gel (75:25 to 50:50 hexane/ethyl acetate) togive 4.34 g (quant) of compound 8a.

  • 2
  • [ 144100-07-2 ]
  • [ 112275-50-0 ]
  • [ 1152093-60-1 ]
YieldReaction ConditionsOperation in experiment
50% With N-ethyl-N,N-diisopropylamine; In ethanol; at 100℃; for 16h; A mixture of 2-bromo-6-fluoropyridine (500 mg, 2.8 mmol), tert-butyl 1,4-diazepane-1-carboxylate (568 mg, 2.8 mmol) in DIPEA (1.83 g, 14.2 mmol) in ethanol (10 mL) was heated at 100 C for 16 hours. The reaction mixture was concentrated under reduced pressure and the residue was diluted with EtOAc (100 mL). The solution was washed with brine, dried over Na2SO4, and concentrated under reduced pressure to afford tert-butyl 4-(6-bromopyridin-2-yl)-1,4-diazepane-1-carboxylate as a colorless oil (500 mg, 50%). MS (ESI) m/z: 356 [M+H] +.
  • 3
  • [ 955368-90-8 ]
  • [ 144100-07-2 ]
  • C14H12FN5OS [ No CAS ]
YieldReaction ConditionsOperation in experiment
With copper(l) iodide; potassium carbonate; N,N-dimethylethylenediamine; In 1,4-dioxane; at 95℃; for 1h;Inert atmosphere; Potassium carbonate (213.62 mg, 1.55 mmol), CuI (213.30 mg, 1.12 mmol, 1.00 eq) and N,N-dimethylethylenediamine (110.58 mg, 1.25 mmol, 134.85 muL) were added into compound I1 (250.00 mg, 1.12 mmol) and 2-bromo-6-fluoropyridine (203.02 mg, 1.15 mmol) in dioxane (8.00 mL) solution. The reaction mixture was stirred under nitrogen atmosphere at 95C for 1 hour. The reaction mixture was cooled down and then ammonia (30 mL) was added, extracted by EtOAc (50 mL×3), the organic phases were combined, the organic phase was washed by saturated brine (50 mL) once, dried over anhydrous sodium sulfate, then filtered, the filtrate was evaporated to give the compound 27-A. MS m/z : 318.0 [M+H]+
 

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