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Chemical Structure| 1150271-74-1 Chemical Structure| 1150271-74-1

Structure of 1150271-74-1

Chemical Structure| 1150271-74-1

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Product Details of [ 1150271-74-1 ]

CAS No. :1150271-74-1
Formula : C13H17BBrFO2
M.W : 314.99
SMILES Code : CC1(C)C(C)(C)OB(C2=CC=C(CBr)C(F)=C2)O1
MDL No. :MFCD11855987

Safety of [ 1150271-74-1 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H314
Precautionary Statements:P301+P330+P331-P303+P361+P353-P363-P304+P340-P310-P321-P260-P264-P280-P305+P351+P338-P405-P501
Class:8
UN#:3261
Packing Group:

Computational Chemistry of [ 1150271-74-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 18
Num. arom. heavy atoms 6
Fraction Csp3 0.54
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 75.71
TPSA ?

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

18.46 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

3.57
Log Po/w (WLOGP)?

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

3.29
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.

2.8
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

3.29
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.59

Water Solubility

Log S (ESOL):?

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

-4.16
Solubility 0.022 mg/ml ; 0.0000697 mol/l
Class?

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

Moderately soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-3.64
Solubility 0.0716 mg/ml ; 0.000227 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

-5.51
Solubility 0.000964 mg/ml ; 0.00000306 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

Yes
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

Yes
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.

-5.69 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

2.0 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)

3.07

Application In Synthesis of [ 1150271-74-1 ]

* 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 [ 1150271-74-1 ]

[ 1150271-74-1 ] Synthesis Path-Downstream   1~9

  • 1
  • [ 903895-56-7 ]
  • [ 1150271-74-1 ]
  • 2
  • [ 1150271-74-1 ]
  • 2-(4-(azidomethyl)-3-fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane [ No CAS ]
  • 3
  • [ 1150271-74-1 ]
  • [ 1418201-59-8 ]
  • 4
  • [ 1150271-74-1 ]
  • [ 1418201-60-1 ]
  • 5
  • [ 1150271-74-1 ]
  • [ 1418201-61-2 ]
  • 6
  • [ 5325-20-2 ]
  • [ 1150271-74-1 ]
  • 4-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)-2H-benzo[b][1,4]thiazin-3(4H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In N,N-dimethyl-formamide; at 60.0℃; for 3h;Inert atmosphere; j00634j 2-(4-(Bromomethyl)-3 -fluorophenyl)-4,4,5,5-tetramethyl- 1,3 ,2-dioxaborolane was prepared in three steps from 4-bromo-2-fluoro-1-methylbenzene following the procedure of White, J.R., et al., Tetrahedron Leu. 2010, 51, 3913-3917. In a dry round bottom flask equipped with a stir bar and septum, 2H-benzo[b][1,4]thiazin-3(4H)-one (90 mg, 0.545 mmol), 2-(4-(bromomethyl)-3 -fluorophenyl)-4,4,5,5 -tetramethyl- 1,3,2- dioxaborolane (150 mg, 0.476 mmol), and potassium carbonate (90 mg, 0.652 mmol) were massed. The flask was purged with argon then charged with dry DMF (3 mL). The reaction was stirred at 60 C and monitored by LCMS. After 3 h, reaction was deemed to be complete and cooled to room temperature. The reaction was diluted with ethyl acetate (20 mL), and the organic layer was washed with saturated NaHCO3. The two layers were separated and the aqueous layer was extracted with ethyl acetate (3x20 mL). The organic extracts were combined then washed with saturated LiC1 solution (20 mL) and brine (20 mL). The organic portion was dried over MgSO4, filtered, and concentrated in vacuo. The crude residue was purified by flash column chromatography on silica gel, eluting with hexanes/ethyl acetate to afford 4-(2-fluoro-4-(4,4,5 ,5 -tetramethyl- 1,3 ,2-dioxaborolan-2- yl)benzyl)-2H-benzo[b][1,4]thiazin-3(4H)-one
  • 7
  • [ 1150271-74-1 ]
  • N-methyl [2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl]methylcarbamate [ No CAS ]
  • 8
  • [ 1150271-74-1 ]
  • [ 74-89-5 ]
  • 1-[2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-N-methylmethanamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran; for 3h; 2.0 M Methylamine in THF (3 mL, 6 mmol) was added dropwise to a solution of <strong>[1150271-74-1]2-[4-(bromomethyl)-3-fluorophenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane</strong> (Combi-Blocks, cat No.PN-5656: 200 mg, 0.6 mmol) in THF (10 mL) over 1 hour. After stirring for an additional 2 h, the reaction was concentrated and used without further purification. LC-MS calculated for C14H22BFNO2 (M+H)+: m/z=266.2. found 266.2.
In tetrahydrofuran; at 20.0℃; for 2h; To a solution of 2.0 M methylamine in tetrahydrofuran (3 mL, 6 mmol) was added dropwise a solution of <strong>[1150271-74-1]2-[4-(bromomethyl)-3-fluorophenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane</strong> (Combi-Blocks, cat PN-5654: 200 mg, 0.6 mmol) in tetrahydrofuran (10 mL). The reaction mixture was stirred at room temperature for 2 h, then concentrated. The crude product was used in the next step without further purification
In tetrahydrofuran; at 20.0℃; for 2h; Step 1: 1-[2-fluoro-4-(4,4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl)phenyl]-N-methylmethanamine To a solution of 2.0 M methylamine in tetrahydrofuran (3 mL, 6 mmol) was added dropwise a solution of <strong>[1150271-74-1]2-[4-(bromomethyl)-3-fluorophenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane</strong> (Combi-Blocks, catNo.PN-5654: 200 mg, 0.6 mmol) in tetrahydrofuran (10 mL). The reaction mixture was stirred at room temperature for 2 h, then concentrated. The crude product was used in the next step without further purification.
  • 9
  • [ 1150271-74-1 ]
  • [ 133240-06-9 ]
  • [ 76-05-1 ]
  • (4-((2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridin-3-yl)methyl)-3-fluorophenyl)boronic acid trifluoroacetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Intermediate 264a was prepared in a similar manner as for Intermediate OOld, replacing 2-(4-(bromomethyl)phenyl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane with 2- (4-(bromomethyl)-3-fluorophenyl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane. Intermediate 264a was purified by preparative HPLC (method E). LC-MS (Method A5): 0.62 min, [M + H]+ = 328.0; H NMR (400 MHz, MeOH-d4 delta 7.54 - 7.42 (m, 2H), 7.39 (s, IH), 7.30 (t, 7=7.6 Hz, IH), 5.83 (s, 2H), 3.26 (q, 7=7.7 Hz, 2H), 2.72 - 2.66 (m, 6H), 1.41 (t, 7=7.6 Hz, 3H).
 

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