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Structure of 1150114-75-2

Chemical Structure| 1150114-75-2

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Product Details of [ 1150114-75-2 ]

CAS No. :1150114-75-2
Formula : C9H13BN2O2
M.W : 192.02
SMILES Code : OB(O)C1=CC=C(N=C1)N1CCCC1
MDL No. :MFCD06801704
Boiling Point : No data available
InChI Key :XRIDMVCUHIKAFT-UHFFFAOYSA-N
Pubchem ID :46737701

Safety of [ 1150114-75-2 ]

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

Computational Chemistry of [ 1150114-75-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 6
Fraction Csp3 0.44
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 58.7
TPSA ?

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

56.59 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

0.7
Log Po/w (WLOGP)?

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

-1.02
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.

-0.19
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

-0.83
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.27

Water Solubility

Log S (ESOL):?

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

-1.66
Solubility 4.23 mg/ml ; 0.022 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.

-1.47
Solubility 6.57 mg/ml ; 0.0342 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

-1.36
Solubility 8.31 mg/ml ; 0.0433 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.

-6.97 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)

2.17

Application In Synthesis of [ 1150114-75-2 ]

* 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 [ 1150114-75-2 ]

[ 1150114-75-2 ] Synthesis Path-Downstream   1~13

  • 1
  • [ 1150114-75-2 ]
  • [ 1222799-84-9 ]
  • [ 1222878-32-1 ]
  • 2
  • [ 1002127-25-4 ]
  • [ 1150114-75-2 ]
  • C23H23F3N2O2 [ No CAS ]
  • 3
  • [ 1268867-67-9 ]
  • [ 1150114-75-2 ]
  • [ 1268864-90-9 ]
  • 4
  • [ 1268867-67-9 ]
  • [ 1150114-75-2 ]
  • [ 1396750-22-3 ]
YieldReaction ConditionsOperation in experiment
55% With caesium carbonate; copper(l) chloride;1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; In N,N-dimethyl-formamide; at 100℃; for 0.5h;Inert atmosphere; Step 1. Methyl 3-(isopropyl(methyl)amino)-2-(6-(pyrrolidin- l-yl)pyridin-3-yl)quinoxaline-6- carboxylateTo a solution of 6-(pyrrolidin- l-yl)pyridin-3-ylboronic acid (244.9 mg, 1.28 mmol) in N,N- dimethylformamide (6 mL) was added 2-chloro-3-(isopropyl(methyl)amino)quinoxaline-6- carboxylate (170.0 mg, 0.58 mmol), Pd(OAc)2 (17.2 mg, 0.03 mmol), DPPF (28.3 mg, 0.05 mmol), CuCl (50.5 mg, 0.51 mmol) and Cs2CC>3 (332.4 mg, 1.02 mmol) with stirring for 0.5 h at 100C with an inert atmosphere of nitrogen. The reaction mixture was cooled and extracted with ethyl acetate (3 x 80 mL), dried over anhydrous magnesium sulfate and concentrated under vacuum. The residue was purified by a silica gel column with 2.5% ethyl acetate in petroleum ether to afford methyl 3-(isopropyl(methyl)amino)-2-(6-(pyrrolidin-l - yl)pyridin-3-yl)quinoxaline-6-carboxylate as a light yellow solid (130.0 mg, 55%).LC/MS (ES, m/z): [M+H]+ 406.0'H-NMR (300 MHz, DMSO) delta 8.69 (d, / = 2.1 Hz, 1H), 8.24 (d, / = 0.9 Hz, 1H), 8.08 (d, / = 2.4 Hz, 1H), 7.91 - 7.99 (m, 1H), 7.66 - 7.70 (m, 1H), 6.59 (d, / = 9.0 Hz, 1H), 4.22 - 4.31 (m, 1H), 3.92 (s, 3H), 3.40 - 3.49 (m, 4H), 2.71 (s, 3H), 1.93 - 1.99 (m, 4H), 1.18 (d, / = 6.6 Hz, 3H), 1.09 (d, / = 6.6 Hz, 3H)
YieldReaction ConditionsOperation in experiment
General procedure: A solution of 5-bromo-N,N-dimethylpyridin-2-amine (500 mg, 2.5 mmol) in THF (10 mL) was treated with n-BuLi (1.2 mL, 3 mmol) at -72 C. for 2 hours. Triisopropyl borate (705 mg, 3.75 mmol) was then added dropwise. After the completion of the addition, the mixture was stirred at -72 C. for an additional 1 hour and slowly warmed up and stirred at the ambient temperature overnight. MeOH was carefully added, and the volatiles were removed under reduced pressure to give the title compound. MS (m/z): 167 (M+H)+.
  • 6
  • [ 1192885-47-4 ]
  • [ 1150114-75-2 ]
  • 2-(3-(3-methoxy-5-methylphenyl)-4-(2-(6-(1-pyrrolidinyl)pyridin-3-yl)pyridin-4-yl)-1H-pyrazole-1-yl)acetonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
92% With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; In tetrahydrofuran; water; at 70℃; for 12.0h;Inert atmosphere; General procedure: A mixture of compound 4 (100 mg, 0.29 mmol), aryl boronic acid (0.35 mmol), bis(triphenylphosphine)palladium(II) dichloride (9 mg, 0.013 mmol) and K2CO3 (71 mg, 0.52 mmol) was placed in a mixed solvent of THF and water (4:1, v/v, 10 mL). N2 gas was bubbled into this mixture for 10 min, and then the mixture was heated at 70 C while stirring under N2 for 12 h. The reaction mixture was left to cool at room temperature, and extracted with ethyl acetate (100 mL × 3). The combined organic extracts were dried over anhydrous MgSO4 and evaporated under vacuum. The target compounds 5a-j were separated in pure form by column chromatography (silica gel) using the proper ratio of ethyl acetate and n-hexane.
  • 7
  • [ 1809-20-7 ]
  • [ 1150114-75-2 ]
  • diisopropyl (6-(pyrrolidin-1-yl)pyridin-3-yl)phosphonate [ No CAS ]
YieldReaction ConditionsOperation in experiment
69% With triphenylphosphine; palladium dichloride; silver(l) oxide; at 100℃; for 2.0h;Inert atmosphere; General procedure: A dried glass reaction tube equipped with a magnetic stir bar was charged with PdCl2 (15.9 mg,0.09 mmol, 15 mol %), PPh3 (314.7 mg, 1.2 mmol, 200mol %), Ag2O (278.1 mg, 1.2 mmol, 200 mol %), aryl (hetero)boronic acid (0.72 mmol, 1.2 equiv) and phosphite ester (0.6 mmol, 1.0 equiv), DMA(3.0 mL, without any purification) was added and the mixture was charged with N2 three times. The reaction mixture was then stirred at 100 C under N2 for 2h. The reaction progress was monitored by TLC. After cooling to room temperature, the reaction mixture was filtered through a pad of celite, and washed with ethyl acetate. The yields of standard reaction were obtained by HPLC. The combined organic solvent was concentratedin vacuo. The residue was purified by silica gel flash chromatography to produce the desired product.
  • 8
  • [ 1150114-75-2 ]
  • [ 33443-53-7 ]
  • 4-phenyl-6-[6-(pyrrolidin-1-yl)pyridin-3-yl]quinazolin-2(1H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
54% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In water; N,N-dimethyl-formamide; at 140℃;Microwave irradiation; General procedure: A mixture of 6-bromo-4-phenylquinazolin-2(1H)-one (200 mg, 0.66 mmol, 1 eq.), DMF (1.5 mL), H2O (0.6 mL), 4-pyridylboronic acid (106 mg, 0.864 mmol, 1.3 eq.), Pd(PPh3)4 (53 mg, 0.046 mmol, 0.07 eq.), and sodium carbonate (162 mg, 1.52 mmol, 2.3 eq.) in a microwave vessel (2 - 5 mL) was heated in the microwave at 140 C for 4 - 24 min. After completion of the reaction (monitored by LC/MS), the mixture was allowed to cool to room temperature, and H2O (8 mL) was added. The resulting precipitate was collected by vacuum filtration and washed with H2O and diethyl ether to afford the crude product as a solid. The crude product was dissolved in a minimal amount of 1,4-dioxane (1 - 10 mL) and any insoluble material was removed by vacuum filtration. A solution of HCl in dioxane (4.0 M) was then added dropwise until a precipitate was formed. The resulting precipitate was collected by vacuum filtration. All Suzuki reactions followed this general procedure, using the appropriate boronic acid, unless otherwise noted.
  • 9
  • 9-bromo-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one [ No CAS ]
  • [ 1150114-75-2 ]
  • 9-(6-(pyrrolidin-1-yl)pyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
83.3% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; at 80℃; for 4.0h; General procedure: To a solution of compound 3(4.18 g, 10 mmol) in 1,4-dioxane at room temperature, we subsequentlyadded Pd(PPh3)4 (1.16 g, 1 mmol), K2CO3 (2.76 g, 20 mmol),and (2-oxoindolin-5 -yl)boronic acid (2.12 g, 12 mmol). Afterdegassing, the resulting mixture was heated to 80 C for 4 h beforecooling to room temperature. The solution was extracted withEtOAc. The organic layer was washed with water and brine, dried(MgSO4), filtered, and evaporated to dryness as a yellow solid. (3.89 g, 82.6% yield)
  • 10
  • [ 121-43-7 ]
  • [ 210963-93-2 ]
  • [ 1150114-75-2 ]
YieldReaction ConditionsOperation in experiment
53% Add SM17 (10.00g, 44.03mmol) to a 250ml three-necked flask containing THF (tetrahydrofuran) (50ml), add n-butyllithium (1.44g, 22.42mmol) dropwise at -78 C, and keep it for 1h after the addition Trimethyl borate (3.33g, 32.03mmol) was added dropwise, the temperature was continued for 1h, and the temperature was raised to room temperature and stirred overnight. Hydrochloric acid (2mol / L) was added to adjust the pH to neutral, and then filtered to obtain a crude white product, which was slurried with n-heptane to obtain a white solid intermediate I-P-1 (4.45g, yield 53%).
  • 11
  • [ 1150114-75-2 ]
  • C21H19BN2O3 [ No CAS ]
  • 12
  • [ 1150114-75-2 ]
  • C36H27N5O [ No CAS ]
  • 13
  • [ 86-76-0 ]
  • [ 1150114-75-2 ]
  • C21H18N2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% With tetrakis(triphenylphosphine) palladium(0); tetrabutyl-ammonium chloride; potassium carbonate; In ethanol; water; toluene; at 78℃; for 10.0h;Inert atmosphere; Intermediate IA (3.0g, 12.14mmol), intermediate IP-1 (3.11g, 16.18mmol), tetrakis (triphenylphosphine) palladium (0.70g, 0.61mmol), potassium carbonate (3.36g, 24.28mmol) , Tetrabutylammonium chloride (0.17g, 0.61mmol), toluene (30mL), ethanol (16mL) and deionized water (8mL) were added to the round bottom flask, heated to 78 C under nitrogen protection, and stirred for 10 hours; The reaction solution was cooled to room temperature, toluene (200 mL) was added for extraction, the organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the solvent was removed under reduced pressure; the resulting crude product was purified by silica gel column chromatography using n-heptane as the mobile phase, and then used The dichloromethane / ethyl acetate system was purified by recrystallization to obtain the intermediate IP-2 (4.22 g, yield 83%
 

Historical Records

Technical Information

Categories

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[ 1150114-75-2 ]

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[ 1150114-75-2 ]

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