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Chemical Structure| 889865-34-3 Chemical Structure| 889865-34-3

Structure of 889865-34-3

Chemical Structure| 889865-34-3

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Product Details of [ 889865-34-3 ]

CAS No. :889865-34-3
Formula : C22H34BNO5
M.W : 403.32
SMILES Code : CC1(C)C(C)(C)OB(C2=CC=C(OC3CCN(C(OC(C)(C)C)=O)CC3)C=C2)O1
MDL No. :MFCD22418284
InChI Key :XPNSYBYHVPMAET-UHFFFAOYSA-N
Pubchem ID :59320843

Safety of [ 889865-34-3 ]

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

Computational Chemistry of [ 889865-34-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 29
Num. arom. heavy atoms 6
Fraction Csp3 0.68
Num. rotatable bonds 6
Num. H-bond acceptors 5.0
Num. H-bond donors 0.0
Molar Refractivity 119.08
TPSA ?

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

57.23 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

4.32
Log Po/w (WLOGP)?

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

3.38
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.

2.19
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

2.39
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.46

Water Solubility

Log S (ESOL):?

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

-4.82
Solubility 0.00611 mg/ml ; 0.0000152 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.

-5.24
Solubility 0.00234 mg/ml ; 0.00000581 mol/l
Class?

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

Moderately 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

-5.05
Solubility 0.0036 mg/ml ; 0.00000893 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

Yes
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

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<2.0
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)

3.74

Application In Synthesis of [ 889865-34-3 ]

* 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 [ 889865-34-3 ]

[ 889865-34-3 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 808744-34-5 ]
  • [ 889865-34-3 ]
  • tert-butyl 4-(4-imidazo[1,2-a]pyridin-7-ylphenoxy)piperidine-1-carboxylate hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
62% Palladium acetate (0.021 g, 0.094 mmol) and triphenylphosphine (0.10 g, 0.38 mmol) were combined in a flask in 1,4-dioxane (6.0 mL). After stirring for 30 mi DMF (5.7 g, 6.0 mL, 78 mmol), tert-butyl 4-[4-(4,4,5,5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl)phenoxyj piperidine- 1- carboxylate (0.75 g, 1.9 mmol), 7-bromoimidazo[1,2-ajpyridine (0.44 g, 2.2 mmol) and aq. Na2CO3 (0.5 M) (12.0 mL, 6.0 mmol) were added and the flask was heated under nitrogen at 90C overnight. The mixture was diluted with water (60 mL) then extracted with EtOAc (3x50 mL). The organic extracts were combined, washed with brine (50 mL), dried over sodium sulfate filtered and concentrated in vacuo. The residue was dissolved in EtOAc (40 mL) then treated with 2M HC1 in ether (1.5 mL) with stirring. The resultant solids were collected by filtration,
  • 2
  • [ 876343-10-1 ]
  • [ 889865-34-3 ]
  • tert-butyl 4-(4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-6-yl)phenoxy)piperidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
1.039 g With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 3h;Inert atmosphere; A mixture of <strong>[876343-10-1]4-chloro-6-iodo-7H-pyrrolo[2,3-d]pyrimidine</strong> (Synnovator, Inc., CAS[ 876343-10-1]) (855 mg, 3.06 mmol), Cs2C03 (2492 mg, 7.65 mmol) and tert-butyl 4-(4-(4,4,5,5-tetramethyl- 1 ,3, 2-dioxaborolan-2-yl)phenoxy)piperidine-1 -carboxylate (step 1) (1234 mg, 3.06 mmol) in dioxane/water 1 :1 (30 ml) was degassed with argon. PdCl2(dppf)-CH2Cl2 adduct (250 mg, 0.306 mmol) was added and the RM was stirred at 100C for 3 h. The RM was cooled to RT and then partitioned between EtOAc and sat. aq. NaHC03. Layers were separated, then the organic layer was washed with brine, dried over MgS04 and concentrated under reduced pressure. Purification of the crude product by flash chromatography on silica gel eluting with 0 - 100% EtOAc in CHX afforded a brown residue. The residue was then triturated with MeOH, the resulting suspension was filtered, washed with Et20 and dried under reduced pressure to afford 1.039 g of the title compound as a beige powder. LC-MS (Method A): Rt = 1.24 min, [M+H]+ = 429.3/431.2.
 

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Technical Information

Categories

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