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Chemical Structure| 89891-65-6 Chemical Structure| 89891-65-6

Structure of 89891-65-6

Chemical Structure| 89891-65-6

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Product Details of [ 89891-65-6 ]

CAS No. :89891-65-6
Formula : C8H4BrClN2
M.W : 243.49
SMILES Code : BrC1=CC=C2C(=C1)N=C(C=N2)Cl
MDL No. :MFCD02955309
InChI Key :AZUMKBQKUXTHCM-UHFFFAOYSA-N
Pubchem ID :4913253

Safety of [ 89891-65-6 ]

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

Computational Chemistry of [ 89891-65-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 10
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 52.25
TPSA ?

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

25.78 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.36
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

2.92
Log Po/w (WLOGP)?

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

3.05
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.

2.17
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

3.25
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.75

Water Solubility

Log S (ESOL):?

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

-3.81
Solubility 0.0381 mg/ml ; 0.000156 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.

-3.12
Solubility 0.184 mg/ml ; 0.000754 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

-4.8
Solubility 0.00384 mg/ml ; 0.0000158 mol/l
Class?

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

Moderately 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.

-5.71 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

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)

1.96

Application In Synthesis of [ 89891-65-6 ]

* 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 [ 89891-65-6 ]

[ 89891-65-6 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 89891-65-6 ]
  • [ 212327-11-2 ]
YieldReaction ConditionsOperation in experiment
54.2% With ammonia; In 1,4-dioxane; at 70.0℃; for 5.0h; a) 7-bromoquinoxaline-2-amine 7-bromo-2-chloroquinoxaline (1.0 g, 4.13 mmol) and ammonia (7 mL) were added to 1,4-dioxane (7 mL). After reaction under agitation at 70 C for 5 h, the reaction mixture was cooled to rt. Water (10 mL) was added, and EA (30 mL*2) was used for extraction. The organic phases were combined, washed with a saturated saline solution (50 mL), dried with anhydrous sodium sulfate, filtered, and concentrated at reduced pressure to obtain a crude compound. Isolation and purification by column chromatography (silica gel, PE: EA = 3:1 as an eluant) were performed to obtain the targeted compound (500 mg, 54.2% yield, yellow solid). LC-MS (ESI): m/z (M+1) 223.99.
With ammonium hydroxide; In 1,4-dioxane; at 110.0℃;Sealed tube; A solution of intermediate 431 ( 1 00 mg, 0.41 mmol) in dioxane (4 niL) and Nu.Eta2Omicron(10 mL, 25%) was stirred in a sealed tube at 1 10C overnight. The mixture was concentrated to give the crude intermediate 432 (108 mg) as a yellow solid.
  • 3
  • [ 89891-65-6 ]
  • [ 885693-20-9 ]
  • tert-butyl 3-(7-bromoquinoxalin-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
14% With potassium phosphate; chloro(2-dicyclohexylphosphino-2?,4?,6?-triisopropyl-1,1?-biphenyl)[2-(2?-amino-1,1?-biphenyl?)]palladium(II); In tetrahydrofuran; water; at 20℃; for 16h;Inert atmosphere; Sealed tube; XPhos second generation precatalyst (40.5 mg, 0.051 mmol) was added to a thick- walled, screw top tube containing an argon-degassed solution of 7-bromo-2- chloroquinoxaline (250 mg, 1.027 mmol), tert-butyl 3-(4,4,5,5-tetramethyl-l,3,2- dioxaborolan-2-yl)-5,6-dihydropyridine-l(2H)-carboxylate (317 mg, 1.027 mmol) and potassium phosphate (545 mg, 2.57 mmol) in THF (5 mL) and water (1 mL). The tube was sealed, and the mixture was stirred at rt for 16 h before it was diluted with ethyl acetate and water. The aqueous layer was separated and the organic layer was extracted twice more with ethyl acetate. The combined organic extract was washed with brine, dried over MgS04, filtered and concentrated to give a light caramel-colored residue. The residue was taken up in a small amount of dichloromethane and charged to a RediSepRf normal phase silica gel Teledyne ISCO 40 g disposable column which was first eluted with hexanes for 120 mL, followed by 0 - 50percent B for 1400 mL where solvent B = ethyl acetate and solvent A = hexanes. After concentration of the eluant, there was isolated the desired product, tert-butyl 3-(7-bromoquinoxalin-2-yl)-5,6-dihydropyridine-l(2H)- carboxylate (56.0 mg, 14percent yield) as a light yellow solid. LCMS: tR (retention time) = 1.51 min; LCMS (ESI) m/z calcd for C18H21BrN302: 390.08, found: 389.95 and 391.95 [M+H]+. LCMS conditions: Injection Vol = 3 uL; Gradient = 2 - 98percent B; Gradient Time = 1.5 min; Flow Rate = 0.8 ml/min; Wavelength = 220 nm; Mobile Phase A = 0: 100 acetonitrile: water with 0.05percent trifiuoroacetic acid; Mobile Phase B = 100:0 acetonitrile:water with 0.05percent trifiuoroacetic acid; Column = Waters Aquity BEH CI 8, 2.1 x 50 mm, 1.7 U (= muiotaeta); Oven Temp = 40 °C. NMR (500MHz, CDCh) delta 9.10 (s, 1H), 8.25 (br. s., 1H), 7.94 (d, J=8.8 Hz, 1H), 7.80 (dd, J=8.8, 2.0 Hz, 1H), 7.04 (br. s., 1H), 4.59 (br. s., 2H), 3.66 (t, J=5.7 Hz, 2H), 2.50 (br. s., 2H), 1.55 (s, 9H).
 

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