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Chemical Structure| 908268-52-0 Chemical Structure| 908268-52-0

Structure of 908268-52-0

Chemical Structure| 908268-52-0

7-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2-a]pyridine

CAS No.: 908268-52-0

4.5 *For Research Use Only !

Cat. No.: A509646 Purity: 96%

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Product Details of [ 908268-52-0 ]

CAS No. :908268-52-0
Formula : C13H17BN2O2
M.W : 244.10
SMILES Code : CC1(C)C(C)(C)OB(C2=CC3=NC=CN3C=C2)O1
MDL No. :MFCD13177254
Boiling Point : No data available
InChI Key :ZZHAKZUFNIDWIA-UHFFFAOYSA-N
Pubchem ID :49758473

Safety of [ 908268-52-0 ]

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

Computational Chemistry of [ 908268-52-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 18
Num. arom. heavy atoms 9
Fraction Csp3 0.46
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 71.67
TPSA ?

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

35.76 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

2.75
Log Po/w (WLOGP)?

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

1.63
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.

0.78
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

0.8
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.19

Water Solubility

Log S (ESOL):?

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

-3.39
Solubility 0.0995 mg/ml ; 0.000407 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.

-3.16
Solubility 0.171 mg/ml ; 0.000698 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

-3.69
Solubility 0.0497 mg/ml ; 0.000204 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

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

Yes
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-5.84 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)

2.8

Application In Synthesis of [ 908268-52-0 ]

* 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 [ 908268-52-0 ]

[ 908268-52-0 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 4532-25-6 ]
  • [ 73183-34-3 ]
  • [ 908268-52-0 ]
YieldReaction ConditionsOperation in experiment
90% Combine <strong>[4532-25-6]7-chloro-imidazo[1,2-a]pyridine</strong> (500.4 g, 3.28 mol), bis(pinacolato)diboron (999 g; 3.93 mol), tricyclohexylphosphine (92 g; 328.06 mmoles), and potassium acetate (483 g; 4.92 mol), in diglyme (4 L) and water (4.83 mL) and stir for 5 min. Add palladium (II) acetate (36.81 g; 163.96 mmoles) and more diglyme (1 L) and heat to 100 C. for 17 hours. Cool the reaction and add potassium carbonate (340 g; 2.46 moles) and stir 18 hr. Filter reaction slurry and wash solids with diglyme (2*1 L). Slurry the solids in water (5 L) and then filter and wash with water (2*1 L) and heptane (1 L). Dry the solid in a vacuum oven at 60 C. to afford 695.1 g (90%) of the titled product. MS (m/z): 245 (M+1).
With potassium acetate;tris-(dibenzylideneacetone)dipalladium(0); tricyclohexylphosphine; In 1,4-dioxane; at 80℃; Preparation 27; 3-Iodo-7-pyridin-2-yl-imidazo[l,2-a]pyridine A. 7-Pyridin-2-yl-imidazo[l,2-a]pyridineTo a round bottomed flask add 7-chloro-imidazo[l,2-a]pyridine (0.25 g, 1.6 mmol), tricyclohexylphosphine (55 mg, 0.12 equiv.), potassium acetate (0.24 g, 1.5 equiv.), bis(pinacolato)diboron (0.46 g, 1.1 equiv.) and dioxane (10 mL). Deoxygenate this mixture thoroughly with N2 then add tris(dibenzylideneacetone)dipalladium (0) (75 mg, 0.05 equiv.) and heat the reaction to 80 C overnight under N2. Filter the reaction thru Celite and wash with DCM then concentrate to dryness. To this residue, add 2- bromopyridine (0.14 mL, 1.5 mmol), S-Phos (75 mg, 0.125 equiv.), potassium phosphate (0.62 g, 2 equiv.), dioxane (10 mL), and water (5 mL). Deoxygenate this mixture thoroughly with N2, add palladium (II) acetate (16 mg, 0.05 equiv.), and reflux the reaction overnight. Concentrate the reaction to dryness and slurry in DCM. Filter this slurry thru Celite and wash with DCM. Concentrate the filtrate then purify by silica column (EtOAc to 5% MeOH : DCM) to give a residue (0.325 g, >100 %). MS (ES), m/z 196 (M+l).
With potassium carbonate; tricyclohexylphosphine;palladium diacetate; In water; diethylene glycol; at 100℃; for 15h;Inert atmosphere; 7-Chloro-imidazo[1,2-a]pyridine (10 g; 65.54 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi-1,3,2-dioxaborolane (19.93 g; 78.65 mmol), K2CO3 (13.59 g; 98.31 mmol), tricyclohexylphosphine (1.84 g; 6.55 mmol), Palladium acetate (47% Pd) (0.74 g; 3.28 mmol) in 2-methoxyethylether (100 ml) and water (0.13 ml) were heated to 100 C. for 15 hours under N2. The reaction mixture was cooled to room temperature. The mixture was cooled to 5 C., filtered, washed the cake with 2×10 ml of water and poured into in 50 ml of water then filtered and the insoluble was washed with 2×20 ml of water, dried to give 11.25 g (70.396) of intermediate shown.
With potassium carbonate; tricyclohexylphosphine;palladium diacetate; In water; at 100℃; To a solution of 7-chloroimidazo-[1 ,2,a]pyridine (10 g, 65.5 mmol) and bis(pinocolato)diboron (20 g, 78.7 mmol) in diglyme (100 ml) were added K2CO3 (13.5 g, 97.7 mmol), palladium (II) acetate (730 mg, 3.25 mmol), tricyclohexylphosphine (1.8 g, 6.42 mmol) and water (0.14 ml). The resulting mixture was heated at 100 0C overnight under an inert atmosphere, diluted with water (50 ml) and stirred for 1 h at room temperature. The precipitate was separated by filtration, washed with diglyme/water (2/1 , 30 ml) and water (20 ml) then dried to generate the product (7.58 g) as a grey powder. MS: [M+H]+ = 246.

  • 2
  • [ 808744-34-5 ]
  • [ 73183-34-3 ]
  • [ 908268-52-0 ]
YieldReaction ConditionsOperation in experiment
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 90℃; for 18h;Sealed tube; Inert atmosphere; Microwave irradiation; In a sealed microwave vial purged with nitrogen, a mixture of 7-bromoimidazo[l,2- ajpyridine (50 mg, 0.254 mmol), bis(pinacolato)diboron (66 mg, 0.260 mmol), potassium acetate (70 mg, 0.713 mmol), and l,l'-bis(diphenylphosphino)ferrocene- palladium(II)dichloride dichloromethane complex (10 mg, 0.012 mmol) in 1,4-dioxane (2 mL) was stirred at 90 C for 18 h to give the boronic ester intermediate, 7-(4 ,4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)imidazo[l,2-a]pyridine. The reaction mixture was cooled to room temperature. 9-[(4-bromo-2-fluorophenyl)methyl]-4-cyclopropyl-l-oxa-4,9- diazaspiro[5.5]undecan-3-one (100 mg, 0.237 mmol), l,l'-bis(diphenylphosphino)ferrocene- palladium(II)dichloride dichloromethane complex (10 mg, 0.012 mmol) and 2M aqueous potassium carbonate solution (1 mL, 2 mmol) were added to the reaction mixture and the resulting mixture was stirred at 100 C for 1 h. The reaction was cooled to room temperature, diluted with ethyl acetate (20 mL) and water (5 mL), and the layers were separated. The aqueous layer was extracted with ethyl acetate (20 mL). The organic layers were combined, dried over MgSC^, and concentrated in vacuo. Purifications by silica gel chromatography (0- 10% methanol/ethyl acetate) followed by reverse phase HPLC (10-70% acetonitrile /water + 0.1% NH4OH) provided the title compound as a beige solid (16 mg, 16%). MS(ES)+ m/e 435.1 [M+H]+.
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 90℃; for 2h;Inert atmosphere; A mixture of <strong>[808744-34-5]7-bromoimidazo[1,2-a]pyridine</strong> (40 mg, 0.164 mmol), (0842) 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) (40 mg, 0.136 mmol), KOAc (93 mg, 0.34 mmol) and Pd(dppf)Cl2.DCM (14 mg, 0.019 mmol) in dioxane (2 mL) was stirred at 90 oC for 2 h under N2 atmosphere. The reaction was concentrated in vacuo and the crude mixture of 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2-a]pyridine was used in the next step without purification. LC-MS m/z: 245.2 [M+H]+. tR = 1.17 min.
 

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