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Structure of 397843-58-2

Chemical Structure| 397843-58-2

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Product Details of [ 397843-58-2 ]

CAS No. :397843-58-2
Formula : C11H16BNO3
M.W : 221.06
SMILES Code : OB(C1=CC=CC(CN2CCOCC2)=C1)O
MDL No. :MFCD08060623
InChI Key :VTSDPGUSDVMXDN-UHFFFAOYSA-N
Pubchem ID :11031409

Safety of [ 397843-58-2 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P280-P305+P351+P338-P310

Computational Chemistry of [ 397843-58-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 16
Num. arom. heavy atoms 6
Fraction Csp3 0.45
Num. rotatable bonds 3
Num. H-bond acceptors 4.0
Num. H-bond donors 2.0
Molar Refractivity 66.24
TPSA ?

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

52.93 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

0.29
Log Po/w (WLOGP)?

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

-1.33
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.

-0.27
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

-0.35
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.33

Water Solubility

Log S (ESOL):?

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

-1.47
Solubility 7.44 mg/ml ; 0.0337 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.

-0.96
Solubility 24.0 mg/ml ; 0.109 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

-1.89
Solubility 2.87 mg/ml ; 0.013 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.

-7.44 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)

1.94

Application In Synthesis of [ 397843-58-2 ]

* 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 [ 397843-58-2 ]

[ 397843-58-2 ] Synthesis Path-Downstream   1~10

  • 1
  • [ 110-91-8 ]
  • [ 51323-43-4 ]
  • [ 397843-58-2 ]
  • 2
  • C19H14BrN3 [ No CAS ]
  • [ 397843-58-2 ]
  • C30H28N4O [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% 3-(Morpholinomethyl)phenylboronic acid (8c). White solid (81% yield by mass; 90% yield by 1H NMR with EtOAc int. std.); 1H NMR (300 MHz, 5% D2O in CD3OD) delta7.69-7.64 (m, 2H), 7.39-7.36 (m, 1H), 7.32-7.27 (m, 1H), 3.68 (m, 4H), 3.53 (s, 2H), 2.47 (m, 4H); 13C NMR (75 MHz, 5% D2O in CD3OD) delta141.1, 136.7, 136.4, 134.1, 132.8, 128.6, 67.5, 64.4, 54.5; IR (CH2Cl2 cast) 3405, 3047, 2957, 2857, 2808, 1652, 1602 cm-1; HRMS (ES, m/z) calcd for C11H17BNO3 (M+H)+222.1296, found 222.1297.
  • 4
  • [ 1025113-70-5 ]
  • [ 397843-58-2 ]
  • 5
  • [ 1239441-18-9 ]
  • [ 397843-58-2 ]
  • [ 1239441-34-9 ]
  • 6
  • [ 1617499-16-7 ]
  • [ 397843-58-2 ]
  • [ 1617499-00-9 ]
YieldReaction ConditionsOperation in experiment
58.13% With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; water; at 120℃; for 1h;Inert atmosphere; Microwave irradiation; 24: 3-(l-Isopropyltriazol-4-yl)-5-[3 (morpholinomethyl) phenyl] pyridin CS2CO3 (858 mg, 2.64 mmol) was added to a solution of <strong>[397843-58-2](3-(morpholinomethyl)phenyl)boronic acid</strong> (250 mg, 0.88 mmol) and 5-bromo-3-(l-isopropyl-lH-[l,2,3]triazol-4-yl)-pyridin-2- ylamine (215 mg, 0.97 mmol) in dioxane: water (8 mL: 4 mL) degassed the reaction mixture for 10 min with nitrogen. Then added Pd(PPh3)4 (50 mg, 0.044 mmol), degassed the reaction mixture for additional 10 min with nitrogen, the reaction mixture was heated to 120 C in microwave for lh. The reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (2x 30mL). Combined organic layers was dried over Na2S04 and concentrated under reduced pressure. Crude product was purified by silica (100-200 mesh) column eluted with 80-90% ethyl acetate in pet-ether to afford 195 mg (Yield: 58.13 %) of the title compound as a pale yellow solid. Product was converted to its HC1 salt by using HC1 in ether (2M) to afford 202 mg as a pale yellow solid. 'HNMR (DMSO-dg, 400 MHz, TMS) delta: 11.60 (lH, br, s), 9.51 (IH, s), 9.04 (IH, s), 8.54 (3H, br, s), 8.37 (IH, s), 7.89-7.88 (IH, d), 7.60-7.52 (2H, m), 4.99-4.92 (IH, m), 4.44 (2H, s), 3.93 (4H, s), 3.23 (2H, s), 3.16 (2H, br, s), 1.60-1.58 (6H, d). LC-MS: mlz = 379.5 (MH+), tR = 0.36, method A.
  • 7
  • [ 1617499-07-6 ]
  • [ 397843-58-2 ]
  • [ 1617499-05-4 ]
YieldReaction ConditionsOperation in experiment
16.7% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 100℃; for 18h;Inert atmosphere; 29: 3-(5-cyclopropyl-l, 3, 4-oxadiazol-2-yl)-5-[ 3-(morpholinomethyl)phenyl]pyridin To a solution of 5-bromo-3-(5-cyclopropyl-[l,3,4]oxadiazol-2-yl)-pyridin-2-ylamine (400 mg; 1.42 mmol) in dioxane (10 mL) and water (6 mL) were added K2CO3 (587 mg; 4.26 mmol), (3- (morpholinomethyl)phenyl)boronic acid (348 mg; 1.56 mmol) in a sealed tube. The reaction mixture was degassed with argon for 30 min, then added Pd(PPh3)4 (82.0 mg; 0.07 mmol) to the reaction mixture. The reaction mixture was stirred for 18 h at 100 C. The reaction mixture was diluted with water (50 mL) extracted with ethyl acetate (2 X 50 mL) and organic layer was washed with brine, dried over anhydrous sodium sulphate and concentrated under reduced pressure. Crude compound was purified by column chromatography using 100-200 mesh silica gel and eluted with 100 % ethyl acetate, which is further purified by washing with 30 % chloroform in hexane to afford 90 mg (Yield: 16.7 %) of the title compound, as a yellow colour solid. FontWeight="Bold" FontSize="10" HNMR (DMSO-dg, 400 MHz, TMS) delta: 8.52-8.51 (1H, d), 8.20-8.19 (1H, d), 7.58-7.54 (2H, m), 7.43-7.39 (1H, t), 7.35 (2H, s), 7.31-7.28 (1H, d), 3.59-3.54 (6H, m), 2.40-2.30 (5H, m), 1.20-1.15 (4H, m). LCMS conditions: Column BEH C 18 (2.1 x 50 mm) 1.7 mu M-Phase A 5 mM NH4OAC in H20 M-Phase B ACN T/%B 0/03, 1.5/45, 2.5/45, 3.2/95, 4.7/95, 5/03 Flow 0.4 ml/min Diluent MeOH Drift Tube Temp 55 C Gas Pressure : 30psi Nebulizer Temp : 65% Gain : 500 Purity : 97.21 % tPv = 2.10 min, m/z= 378.2[M+H]+
  • 8
  • bis-(Boc)-7-bromo-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-5-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine [ No CAS ]
  • [ 397843-58-2 ]
  • 7-(3-(morpholinomethyl)phenyl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-5-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
44.1% With tripotassium phosphate; In tetrahydrofuran; water; at 85℃; for 2.5h;Inert atmosphere; Sonication; Intermediate 14A (60 mg, 0.106 mmol), <strong>[397843-58-2](3-(morpholinomethyl)phenyl)boronic acid</strong> (35.3 mg, 0.160 mmol) and tripotassium phosphate (113 mg, 0.532 mmol) were combined in a vial. THF (1.5 mL) and water (0.2 mL) were added and the mixture was degassed by bubbling argon while sonicated. Tetrakistriphenylphosphine (12.31 mg,10.65 .imol) was added and the degassing procedure was repeated. The mixture was heated at 85 C for 2.5h. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (5 mL), water (2 mL) and the layers were mixed and then separated. The organic layer was dried over MgSO4 and concentrated. The crude product was 5purified by silica gel chromatography eluting with a gradient of 0-10% MeOH in DCM (w/ 0.5% NH4OAc added to each eluting solvent). The solid obtained was triturated with ethyl acetate to afford Example 14 (22.7 mg, 44.1% yield) as a white solid. LCMS (M+H) = 460.26. Retention time 0.71 mi LCMS Method B.
  • 9
  • [ 137527-18-5 ]
  • [ 397843-58-2 ]
  • 7-(3-(morpholinomethyl)phenyl)-2-phenyl-4H-chromen-4-one [ No CAS ]
  • 10
  • 6-(4-(4-bromophenyl)piperazin-1-yl)-9-((3aR,4R,6R,6aR)-6-(((tert-butyldimethylsilyl)oxy)methyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-9H-purine [ No CAS ]
  • [ 397843-58-2 ]
  • C40H55N7O5Si [ No CAS ]
 

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Technical Information

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