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Structure of 885277-48-5

Chemical Structure| 885277-48-5

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Product Details of [ 885277-48-5 ]

CAS No. :885277-48-5
Formula : C8H8BrNO2
M.W : 230.06
SMILES Code : O=C(OC)C1=C(Br)N=C(C)C=C1
MDL No. :MFCD08059327
InChI Key :UWRNYQBIUUVTGB-UHFFFAOYSA-N
Pubchem ID :11241687

Safety of [ 885277-48-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 885277-48-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.25
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 48.18
TPSA ?

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

39.19 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.23
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

2.13
Log Po/w (WLOGP)?

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

1.94
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.

1.4
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

2.33
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.0

Water Solubility

Log S (ESOL):?

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

-2.85
Solubility 0.328 mg/ml ; 0.00142 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.

-2.58
Solubility 0.599 mg/ml ; 0.0026 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

-3.35
Solubility 0.103 mg/ml ; 0.000449 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.

-6.19 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)

1.91

Application In Synthesis of [ 885277-48-5 ]

* 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 [ 885277-48-5 ]

[ 885277-48-5 ] Synthesis Path-Downstream   1~10

  • 1
  • [ 67-56-1 ]
  • [ 38116-61-9 ]
  • [ 885277-48-5 ]
YieldReaction ConditionsOperation in experiment
79% Phosphorus oxybromide (21.53 g, 75 mmol) was added to the stirred solution of 2-hydroxy-6- methylnicotinic acid (5 g, 32.7 mmol), pyridine (0.475 mL, 5.88 mmol) in chlorobenzene (100 mL) at room temperature under nitrogen. The reaction mixture was refluxed for 1 h and concentrated under vacuum before treating with an excess of cold methanol. The solution was stirred for an additional 1 h and again concentrated under vacuum. The residue was dissolved in water and pH was adjusted to ~8.0 by adding K2CO3 before extraction of the product with CH2CI2. The organic layer was washed with water and brine solution, dried over anhydrous Na2S04. Filtrate was evaporated completely under reduced pressure to give crude residue. The resulted crude compound was purified by flash column chromatography (100-200 silica mesh, eluent was 30% EtOAc in pet ether) to obtained methyl 2-bromo-6-methylnicotinate (6.1 g, 79% yield) as colorless oil. 1H NMR (400 MHz, CDCI3): d 8.00 (d, /= 7.6 Hz, 1H), 7.18 (d, J = 8.0 Hz, 1H), 3.94 (s, 3H), 2.59 (s, 3H); LCMS (ES) m/z 230.0 (M+H)+
  • 2
  • [ 292638-85-8 ]
  • [ 885277-48-5 ]
  • [ 853179-76-7 ]
YieldReaction ConditionsOperation in experiment
43% Na2C03 (8.43 g, 80 mmol) was added to a solution of <strong>[885277-48-5]methyl <strong>[885277-48-5]2-bromo-6-methylnicotinate</strong></strong> (6.1 g, 26.5 mmol) and methyl acrylate (6.08 mL, 67.1 mmol) in mixture of DMA (16.99 mL, 181 mmol) and toluene (55 mL) at room temperature. Then the reaction mixture was degassed for 15 min. Tri-r olyl phosphine (0.807 g, 2.65 mmol) and allylpalladium chloride dimer (0.4850 g, 1.326 mmol) were added and the reaction mixture was stirred at 115 C in sealed tube for 5 h. Filtered through pad of Celite, and the filtrate was concentrated under reduced pressure. The resultant crude compound was purified by flash column chromatography on 100-200 mesh silica gel using 20% EtO Ac/pet-ether as an eluent to obtained (///-methyl 2-(3-methoxy-3-oxoprop-l- en-l-yl)-6-methylnicotinate (3.30 g, 43.0% yield) as a colorless oil. 1H NMR (400 MHz, CDCE): d 8.53 (dd, /= 1.2, 15.2 Hz, 1H), 8.22 (d, /= 6.8 Hz, 1H), 7.20-7.11 (m, 2H), 3.94 (s, 3H), 3.82 (s, 3H), 2.60 (s, 3H). LCMS (ES) m/z 236.09 (M+H)+
  • 3
  • [ 885277-48-5 ]
  • [ 853179-88-1 ]
  • 4
  • [ 885277-48-5 ]
  • [ 173064-91-0 ]
  • 5
  • [ 7486-35-3 ]
  • [ 885277-48-5 ]
  • [ 1228430-80-5 ]
YieldReaction ConditionsOperation in experiment
tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 20 - 95℃;Inert atmosphere; To a solution of <strong>[885277-48-5]methyl 2-bromo-6-methyl-3-pyridinecarboxylate</strong> D60 (1.15 g) and Pd(Ph3P)4 (0.2 g, 0.173 mmol) in 1,4-Dioxane (10 ml) stirred under nitrogen at room temperature tributyl(ethenyl)stannane (1.74 g, 5.50 mmol) was added neat in one charge. The reaction mixture was stirred at microwave Personal Chemistry at 95 C. for 30 minutes. The solvent was removed to give the crude title compound. Under similar conditions another batch of D60 (100 mg) was processed to give the crude title compound. The two crudes were joined and purified by flash chromatography on silica (80 g column, gradient elution from Cy to Cy/EtOAc 4:6) to afford the title compound D61 (1.0 g). UPLC (Basic GEN_C): rt=0.73 minutes, peak observed: 178 (M+1). C10H11NO2 requires 177. 1H NMR (400 MHz, CDCl3) delta ppm 8.08 (d, 1H), 7.66 (dd, 1H), 7.12 (d, 1H), 6.52 (d, 1H), 5.59 (dd, 1H), 3.93 (s, 3H), 2.63 (s, 3H).
  • 6
  • [ 53277-47-7 ]
  • [ 885277-48-5 ]
YieldReaction ConditionsOperation in experiment
With trimethylsilyl bromide; at 160℃; for 0.333333h;Inert atmosphere; To a stirred solution of methyl 2-chloro-6-methyl-3-pyridinecarboxylate D59 (500 mg) in propionitrile (2 ml) under nitrogen at room temperature bromotrimethylsilane (0.699 ml, 5.39 mmol) was added dropwise neat. The reaction mixture was heated at Microwave Personal Chemistry 20 min at 160 C. The solvent was removed to give the crude. Under similar conditions another batch of D59 (500 mg) was processed to give the crude title compound. The two crudes were joined and purified together by flash chromatography on silica gel (80 g column, Cy 100% to Cy/EtOAc 4:6) to give the title compound D60 (1.2 g). 1H NMR (400 MHz, CDCl3) delta ppm 8.02 (d, 1H), 7.20 (d, 1H), 3.96 (s, 3H), 2.62 (s, 3H)
  • 7
  • (R)-4-(4-(3-ethynylcyclopent-2-en-1-yl)piperazin-1-yl)benzonitrile [ No CAS ]
  • [ 885277-48-5 ]
  • (R)-methyl 2-((3-(4-(4-cyanophenyl)piperazin-1-yl)cyclopent-1-en-1-yl)ethynyl)-6-methylnicotinate [ No CAS ]
YieldReaction ConditionsOperation in experiment
20.90% With bis-triphenylphosphine-palladium(II) chloride; N-ethyl-N,N-diisopropylamine; In acetonitrile; at 70 - 85℃; for 14h;Inert atmosphere; To a stirred solution of <strong>[885277-48-5]methyl <strong>[885277-48-5]2-bromo-6-methylnicotinate</strong></strong> (US2010144760, 2.79 g, 12.1 1 mmol) in acetonitrile (50 ml) (degassed by N2 purge separately) was added bis(triphenylphosphine)palladium(II) chloride (1.063 g, 1.514 mmol). The reaction mixture was heated up to 70 C and diisopropyl ethyl amine (7.83 g, 60.6 mmol) was added slowly, followed by a solution of (R)-4-(4-(3-ethynylcyclopent-2- en- l-yl)piperazin- l-yl)benzonitrile (Compound lj, 2.8 g, 10.10 mmol) in acetonitrile (20 ml) was added slowly at the same temperature. The reaction mixture was heated and stirred at 80-85 C for 14 hrs. The progress of the reaction was monitored by TLC. The reaction mixture was distilled under vaccum to dryness to obtain a crude product which was purified by column chromatography over silica gel (100-200 mesh) using 60-80% ethyl acetate in hexane as an eluent to obtain the title product (0.9 gm, 20.90 % yield). iH NMR (400 MHz, CDC13) delta 8.17 (d, J = 8.1 Hz, 1H), 7.52 (d, J = 8.5 Hz, 2H), 7.20 (d, J = 8.2 Hz, 1H), 6.90 - 6.87 (m, 2H), 6.36 (d, J = 2.3 Hz, 1H), 4.08 - 4.03 (m, 1H), 3.96 (s, 3H), 3.40 - 3.35 (m, 4H), 2.75 - 2.67 (m, 6H), 2.64 (s, 3H), 2.13 - 2.09 (m, 1H), 2.03 - 1.95 (m, 1H). MS: m/z 427.24 (M+l).
  • 8
  • [ 885277-48-5 ]
  • ethyl 2-(4-chloro-6-(2-methyl-6,7-dihydro-5H-cyclopenta[b]pyridin-5-yloxy)benzo[b]thiophen-3-yl)acetate [ No CAS ]
  • 9
  • [ 885277-48-5 ]
  • 2-methyl-6,7-dihydro-5H-cyclopenta[b]pyridin-5-ol [ No CAS ]
  • 10
  • [ 885277-48-5 ]
  • 5-chloro-2-methyl-6,7-dihydro-5H-cyclopenta[b]pyridine [ No CAS ]
 

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Technical Information

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