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Chemical Structure| 476342-37-7

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Product Details of [ 476342-37-7 ]

CAS No. :476342-37-7
Formula : C10H15N3O
M.W : 193.25
SMILES Code : NC1=CC=C(N=C1)N1CCC(O)CC1
MDL No. :MFCD09728697
InChI Key :JFSQCTGGZLCLFF-UHFFFAOYSA-N
Pubchem ID :16781994

Safety of [ 476342-37-7 ]

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

Computational Chemistry of [ 476342-37-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 6
Fraction Csp3 0.5
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 2.0
Molar Refractivity 59.25
TPSA ?

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

62.38 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.27
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

0.5
Log Po/w (WLOGP)?

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

0.25
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.

0.38
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

0.38
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.56

Water Solubility

Log S (ESOL):?

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

-1.6
Solubility 4.81 mg/ml ; 0.0249 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.

-1.38
Solubility 8.06 mg/ml ; 0.0417 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

-1.59
Solubility 4.99 mg/ml ; 0.0258 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.

-7.12 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

1.0
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<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)

2.26

Application In Synthesis of [ 476342-37-7 ]

* 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 [ 476342-37-7 ]

[ 476342-37-7 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 353258-16-9 ]
  • [ 476342-37-7 ]
YieldReaction ConditionsOperation in experiment
89% With hydrogen;palladium 10% on activated carbon; In ethanol; at 20℃; for 3.0h; Example 18C. l-(5-Aminopyridin-2-yl)piperidin-4-ol [00153] A solution of l-(5-nitropyridin-2-yl)piperidin-4-ol (Example, 18B, 0.6g, 2.6 mmol) in ethanol was added 10% palladium on carbon (0.3 g) and the mass was stirred at RT with hydrogen bladder for 3 h. Reaction mass was filtered through CELITE and concentrated to remove ethanol to yield Example 18C (0.45 g, 89% yield) as a brown oil. LC-MS, [M+H]+ = 194. 1U NMR (CD3OD, 400MHz): delta 7.70 (d, J = 2.6 Hz, IH), 7.10 (dd, J = 2.6, 8.8 Hz, IH), 6.73 (d, J = 8.8 Hz, IH), 3.76 (m, 3H), 2.91 (m, 2H), 1.89 (m, 2H), 1.51 (m, 2H).
51% With hydrogenchloride; iron; In ethanol; water; at 90℃; for 2.0h; To a suspension of 1.35g (6.04mmol) of the compound obtained in the Manufacturing Example 73 in 18mL of ethanol and 3mL of water were added 1.3g of reduced iron and 0.25mL of conc. hydrochloric acid, and the mixture was stirred for 2 hours at 90C. After cooling the reaction mixture, the mixture was filtrated by Celite and filtrate was condensed under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: dichloromethane/methanol = 10/1) to give 601mg (51%) of the title compound.
YieldReaction ConditionsOperation in experiment
99.5% With palladium 10% on activated carbon; hydrogen; In ethanol; at 20℃; for 5.0h; General procedure: 10%) Palladium on carbon (0.095g) was added to a solution of 3'- fluoro-3 -nitrobiphenyl (L) (0.63 g, 2.88 mmol) in EtOH (20.0 mL). The flask was evacuated and replaced with a hydrogen atmosphere. The solution was stirred at room temperature for 5 h under hydrogen. The catalyst was filtered through a pad of Celite, and the solvent was removed under reduced pressure. The residue was purified by flash chromatography using a 40 g Thomson normal phase silica gel cartridge (100% hexanes ? 15:85 EtOAc:hexanes) to afford 3'-fluoiObiphenyl-3-amine (LI) (0.34 g, 1.81 mmol, 63% yield) as a light yellow oil. 1H NMR (DMSO-d6) delta ppm 7.47-7.44 (m, 1H), 7.40- 7.39 (m, 1H), 7.36-7.33 (m, 1H), 7.15-7.14 (m, 1H), 7.10 (t, J=7.7Hz, 1H), 6.85-6.84 (m, 1H), 6.80-6.79 (m, 1H), 6.60-6.58 (m, 1H), 5.18 (s, 2H); ESIMS found for C12H10FN mlz 188 (M+H).
99.5% With palladium 10% on activated carbon; hydrogen; In ethanol; at 20℃; for 6.0h; General procedure: Step 2 10% Palladium on carbon (40 mg) was added to a solution of 1-methyl-4-(5-nitropyridin-2-yl)piperazine (LIX) (3.80 g, 17.09 mmol) in EtOH (50.0 mL). The flask was evacuated and replaced with a hydrogen atmosphere. The solution was stirred at room temperature for 6 h under hydrogen. The catalyst was filtered through a pad of Celite, and the solvent was removed under reduced pressure to afford 6-(4-methylpiperazin-1-yl)pyridin-3-amine (LX) as a brown viscous oil which solidified under vacuum (3.30 g, 17.1 mmol, quantitative).
99.5% With palladium 10% on activated carbon; hydrogen; In ethanol; at 20℃; for 6.0h; General procedure: 10% Palladium on carbon (0.095g) was added to a solution of 3'-fluoro-3- nitrobiphenyl (L) (0.63 g, 2.88 mmol) in EtOH (20.0 mL). The flask was evacuated and replaced with a hydrogen atmosphere. The solution was stirred at room temperature for 5 h under hydrogen. The catalyst was filtered through a pad of Celite, and the solvent was removed under reduced pressure. The residue was purified by flash chromatography using a 40 g Thomson normal phase silica gel cartridge ( 100% hexanes? 15 : 85 EtOAc:hexanes) to afford 3'-fluorobiphenyl-3-amine (LI) (0.34 g, 1.81 mmol, 63% yield) as a light yellow oil.
Preparation of 5'-amino-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-ol With a method similar to that used for the preparation of 6-morpholin-4-yl-pyridin-3-ylamine above, 5'-amino-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-ol was prepared from 2-chloro-5-nitro-pyridine and piperidin-4-ol. LCMS calcd for C10H15N3O (m/e) 193, obsd 194 (M+H).

  • 3
  • [ 476342-37-7 ]
  • [ 1221420-34-3 ]
  • [ 1221420-36-5 ]
YieldReaction ConditionsOperation in experiment
Example 18D. 4-(4-Chlorophenyl)- 1 -((dimethylamino)methyleneamino)-N-(6-(4- hydroxypiperidin- 1 -yl)pyridin-3-yl)- lH-pyrrole-2-carboxamide[00154] To a mixture of 5-(4-chlorophenyl)-2-(dimethylamino-methyleneamino)- 2H-pyrazole-3-carboxylic acid (Example 18A, 0.175 g, 0.59mmol) and DMF (2 mL) was added EtaOBT (0.039g, 0.3mmol), EDCI HCl (0.33 g, 1.7mmol) and DIPEA (0.15g, 1.18mmol). The resulting mixture was stirred at room temperature for 15 min. Example 18C was then added and the mixture was stirred at room temperature overnight. Reaction mass was quenched into water, solid obtained was filtered and washed with water. Pale brown solid (Example 18D, 0.1 g, 37% yield) obtained was taken to the next step without purification. LC-MS, [M+Eta]+ = 467.
  • 4
  • [ 476342-37-7 ]
  • 7-bromo-2-(cyclopentylamino)-3-ethyl-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidine-6-carboxylic Acid [ No CAS ]
  • 7-bromo-2-(cyclopentylamino)-3-ethyl-N-[6-(4-hydroxypiperidin-1-yl)pyridin-3-yl]-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidine-6-carboxamide [ No CAS ]
  • 5
  • [ 476342-37-7 ]
  • C14H14ClN3O2 [ No CAS ]
  • C24H27ClN6O2 [ No CAS ]
 

Historical Records

Technical Information

Categories

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