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Structure of 914347-01-6

Chemical Structure| 914347-01-6

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Product Details of [ 914347-01-6 ]

CAS No. :914347-01-6
Formula : C11H14BrN3O2
M.W : 300.15
SMILES Code : BrC1=CN=C(N=C1)N2CCC(CC2)C(=O)OC
MDL No. :MFCD08275691
InChI Key :CCUNQFMNCAFIEV-UHFFFAOYSA-N
Pubchem ID :45036909

Safety of [ 914347-01-6 ]

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

Computational Chemistry of [ 914347-01-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 17
Num. arom. heavy atoms 6
Fraction Csp3 0.55
Num. rotatable bonds 3
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 70.08
TPSA ?

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

55.32 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

2.64
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

1.7
Log Po/w (WLOGP)?

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

1.25
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.

1.39
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

1.59
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.72

Water Solubility

Log S (ESOL):?

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

-2.84
Solubility 0.439 mg/ml ; 0.00146 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.

-2.48
Solubility 1.0 mg/ml ; 0.00333 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

-3.06
Solubility 0.259 mg/ml ; 0.000863 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

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

Yes
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.

-6.92 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

0.0 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<0.0
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)

2.46

Application In Synthesis of [ 914347-01-6 ]

* 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 [ 914347-01-6 ]

[ 914347-01-6 ] Synthesis Path-Downstream   1~9

  • 1
  • [ 914347-01-6 ]
  • [ 73183-34-3 ]
  • [ 1160790-50-0 ]
YieldReaction ConditionsOperation in experiment
A solution of methyl-1-(5-bromopyrimidin-2-yl)piperidine-4-carboxylate (0.32 g, 1.05 mmol), bispinacolatodiboron (0.32 g, 1.25 mmol) and KOAc (0.16 g, 1.60 mmol) in 1 ,4-dioxane (5.0 mL) was degassed by flushing with nitrogen for 15 min. Tricyclohexylphosphine (0.036 g, 0.13 mmol) and tris(dibenzyledineacetone) dipalladium (0) (0.05 g, 0.053 mmol) was then added to the reaction mixture, which was again degassed by nitrogen for 15 min. The resulting reaction mixture was heated to 1000C for 4 h. After the completion of the reaction (TLC monitoring), the reaction mixture was filtered through celite bed and the filtrate was concentrated to get the crude residue that was carried forward to the next step without further purification. MS: 348.21 (M+H)+.
900 mg With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 90℃; for 12h;Inert atmosphere; A mixture of methyl l-(5-bromopyrimidin-2-yl)piperidine-4-carboxylate (1.0 g, 3.33 mmol, 1 eq), bis(pinacolato)diboron (1.69 g, 6.66 mmol, 2 eq), potassium acetate (0.98 g, 10 mmol, 3 eq) and Pd(dppf)C12 (0.24 g, 0.330 mmol, 0.100 eq) in 1,4-dioxane (20 mL) was purged with N2 for 3 times, and the mixture was stirred at 90 C for 12 hours under N2 atmosphere. The reaction mixture was filtered and the filtrate was concentrated in vacuo. Purification by prep-HPLC gave the title compound (900 mg, 2.59 mmol, 77.8% yield) as a yellow solid.
  • 2
  • [ 914347-01-6 ]
  • [ 51656-70-3 ]
  • methyl 1-{5-[2-(tert-butoxy)-2-oxoethyl]pyrimidin-2-yl}piperidine-4-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
28% With tris-(dibenzylideneacetone)dipalladium(0); XPhos; In tetrahydrofuran; at 75℃; for 16h;Inert atmosphere; Step 2: <strong>[914347-01-6]methyl 1-(5-bromopyrimidin-2-yl)piperidine-4-carboxylate</strong> Ex.9a (1 .00 g, 3.33 mmol), freshly prepared tert-butyl 2-(bromozincio)acetate Ex.5a (1 1.7 ml, 9.99 mmol) and dry THF (10 mL) were charged to a flask and the mixture was purged with nitrogen for 5 min. Then Pd2(dba)3 (302 mg, 0.33 mmol) and XPhos (319 mg, 0.67 mmol) were added and the solution was stirred at 75C for Ex.9b 16h. The reaction mixture was concentrated and the residue was diluted with EtOAc and water. After phase separation, the organic layer was washed with brine, dried over MgSO4, filtered and the solution was concentrated to dryness. The crude was purified by flash column chromatography on silica gel eluting with heptane and a gradient of heptane/EtOAc from [100:0] to [50:50]. The desired fractions were combined and concentrate to obtain methyl 1-{5-[2-(tert-butoxy)-2-oxoethyl]pyrimidin-2-yl}piperidine-4-carboxylate Ex.9b (930 mg, 28%) as pale yellow oil.
  • 3
  • [ 2971-79-1 ]
  • [ 32779-36-5 ]
  • [ 914347-01-6 ]
YieldReaction ConditionsOperation in experiment
41% With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 20℃; for 16h; Step 1 : DIPEA (4 mL, 23.20 mmol) was added to 5-bromo-2-chloropyrimidine (3.0 g, 15.50 mmol) in acetonitrile (80 mL). Then, methyl isonipecotate (3.321 g, 23.20 mmol) was added to the solution. The reaction mixture was stirred at rt for Ex.9a 16h. The solvent was concentrated to dryness. Water and EtOAc were added to quench the reaction. The organic layer was separated and concentrated to dryness. The crude material was purified by silica gel column chromatography eluting with heptane and a gradient of heptane/EtOAc from [100:0] to [0:100]. The product fractions were combined and concentrated to dryness to afford methyl 1-(5-bromopyrimidin-2-yl)piperidine-4-carboxylate Ex.9a (1 .84 mg, 41 %) as white solid.
To a solution of methyl 4-piperidinecarboxylate (1.0 g, 6.98 mmol, 1 eq) in ethanol (10 mL) was added DIPEA (4.5 g, 34.92 mmol, 5 eq) the mixture was stirred at room temperature for 15 min, then 5-bromo-2-chloropyrimidine (1.35 g, 6.98 mmol, 1 eq) was added and the mixture was stirred at 70 C for 1 hour. The mixture was concentrated to get methyl l-(5-bromopyrimidin-2- yl)piperidine-4-carboxylate (2 g, 6.66 mmol, 95.41% yield) as a yellow solid used directly in the next step. MS m/e: 302 ([M+H+]+).
  • 4
  • [ 914347-01-6 ]
  • 2-{2-[4-(methoxycarbonyl)piperidin-1-yl]pyrimidin-5-yl}acetic acid hydrochloride [ No CAS ]
  • 5
  • [ 914347-01-6 ]
  • methyl 1-(5[(([4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl)carbamoyl)methyl]pyrimidin-2-yl)piperidine-4-carboxylate [ No CAS ]
  • 6
  • [ 914347-01-6 ]
  • 1-(5-[(([4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl)carbamoyl)methyl]pyrimidin-2-yl)piperidine-4-carboxylic acid [ No CAS ]
  • 7
  • [ 914347-01-6 ]
  • methyl 1-[5-[1-(2,6-dichlorobenzoyl)-3-[3-[[ethyl(methyl)sulfamoyl]amino]-2,6-difluorobenzoyl]pyrrolo[2,3-b]pyridin-5-yl]pyrimidin-2-yl]piperidine-4-carboxylate [ No CAS ]
  • 8
  • [ 914347-01-6 ]
  • 1-[5-[3-[3-[[ethyl(methyl)sulfamoyl]amino]-2,6-difluorobenzoyl]-1H-pyrrolo[2,3-b]pyridin-5-yl]pyrimidin-2-yl]piperidine-4-carboxylic acid [ No CAS ]
  • 9
  • [ 914347-01-6 ]
  • N-[1-[4-[(2,6-dioxo-3-piperidyl)amino]-2-fluorophenyl]-4-piperidyl]-1-[5-[3-[3-[[ethyl(methyl)sulfamoyl]amino]-2,6-difluorobenzoyl]-1H-pyrrolo[2,3-b]pyridin-5-yl]pyrimidin-2-yl]piperidine-4-carboxamide [ No CAS ]
 

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Technical Information

Categories

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