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Chemical Structure| 1036381-91-5 Chemical Structure| 1036381-91-5

Structure of 1036381-91-5

Chemical Structure| 1036381-91-5

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Product Details of [ 1036381-91-5 ]

CAS No. :1036381-91-5
Formula : C13H18N2O3
M.W : 250.29
SMILES Code : O=C(N1CC2=C(NC(C=C2)=O)CC1)OC(C)(C)C
MDL No. :MFCD20040076
InChI Key :SYYLNESTCFDFBW-UHFFFAOYSA-N
Pubchem ID :59756839

Safety of [ 1036381-91-5 ]

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

Computational Chemistry of [ 1036381-91-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 18
Num. arom. heavy atoms 6
Fraction Csp3 0.54
Num. rotatable bonds 3
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 72.25
TPSA ?

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

62.4 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.54
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

0.48
Log Po/w (WLOGP)?

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

1.14
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.

1.31
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

2.03
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.5

Water Solubility

Log S (ESOL):?

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

-1.74
Solubility 4.52 mg/ml ; 0.0181 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.

-1.36
Solubility 10.9 mg/ml ; 0.0437 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

-3.0
Solubility 0.249 mg/ml ; 0.000993 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

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.

-7.49 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)

2.47

Application In Synthesis of [ 1036381-91-5 ]

* 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 [ 1036381-91-5 ]

[ 1036381-91-5 ] Synthesis Path-Downstream   1~12

  • 1
  • [ 601514-58-3 ]
  • [ 24424-99-5 ]
  • [ 1036381-91-5 ]
YieldReaction ConditionsOperation in experiment
With hydrogen; N-ethyl-N,N-diisopropylamine;palladium dihydroxide; In ethanol; under 4654.46 Torr; The Step 2 product (2 g, 8.32 mmol) was weighed into a Parr shaker bottle and dissolved in 20 mL of EtOH. Hunigs base (4.34 mL, 25 mmol), (Boc) 20 (2.36 g, 10.8 mmol) and catalyst (0.234 g, 1.7 mmol) were added. The bottle was placed on the Parr shaker and flushed 3* with H2. The reaction was placed under 90 psi H2 and left over the weekend. The reaction was filter through a glass frit packed with celite. The bottle was rinsed 3* with 5 mL MeOH and passed through the frit as well. The volatiles were evaporated and the residue dissolved in 10 mL of DCM. The solution was extracted with sat. bicarbonate. The organic layer was dried with sodium sulfate, filtered through a glass wool plug and the volatiles evaporated. This yielded a white solid, tert-butyl 3-bromo-2-oxo-1,2,7,8-tetrahydro-1,6-naphthyridine-6(5H)-carboxylate, (2.05 g). MS [M+H]+=251.13.
  • 2
  • [ 1036381-91-5 ]
  • [ 1036381-92-6 ]
YieldReaction ConditionsOperation in experiment
With pyridinium hydrobromide perbromide; In dichloromethane; for 0.0833333h; Preparation of tert-butyl 3-bromo-2-oxo-1,2,7,8-tetrahydro-1,6-naphthyridine-6(5H)-carboxylate The Step 3 product (100 mg, 0.4 mmol) dissolved in 2 mL of DCM in a 20 mL scintillation vial containing a stir bar. Big chunks of the pyridinium tribromide (142 mg, 0.4 mmol) have to be crushed up to make them dissolve. The reaction was checked by LCMS after everything dissolved (5 minutes) and the starting material was gone. 5 mL of saturated bicarbonate was added to the orange solution. There was a great deal of bubbling and the organic layer became yellow. The organic layer was removed to a new 20 mL vial and dried with sodium sulfate, filtered through a glass wool plug and evaporated. The yellow/brown oil was used without further purification. MS [M+H]+=329.04.
  • 3
  • [ 7341-96-0 ]
  • [ 79099-07-3 ]
  • [ 1036381-91-5 ]
YieldReaction ConditionsOperation in experiment
51.8% To a stirred solution of tert-butyl 4-oxopiperidine-l-carboxylate (35.6 g, 178.89 mmol) in chloroform (260 ml) at RT was added pyrrolidine (19 ml, 223.61 mmol) dropwise over 1 h. The reaction mixture was stirred for a further Ih at RT then prop-2-ynamide (16 g, 223.61 mmol) was added and the reaction mixture reluxed under Dean-Stark conditions for 16 h. The cooled reaction mixture was filtered and the filtrate triturated with toluene and re-filtered. The filtrate was evaporated at reduced pressure to give a red / brown viscous liquid that was <n="77"/>purified by FCC (SiO2, eluting with 98:2 chloroform / MeOH) to give the title compound (4.01 g, 51.8%) as a brown oil
  • 4
  • [ 1036381-91-5 ]
  • [ 1190440-39-1 ]
  • [ 1190440-42-6 ]
YieldReaction ConditionsOperation in experiment
With tetra-(n-butyl)ammonium iodide; sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 0 - 20℃;Inert atmosphere; To a solution of tert-butyl 2-oxo-l,5,7,8-tetrahydro-l,6-naphthyridine-6(2H)-carboxylate (0.2 g, 0.8 mmol) in DMF (2 ml) at 0 0C under a nitrogen atmosphere was added dropwise 1- cyclobutylpiperidin-4-yl methanesulfonate (0.223 g, 0.957 mmol) in DMF (1 ml), followed by NaH 60% in mineral oil (0.038 g, 1.60 mmol) and TBAI (0.0591 g, 0.160 mmol). The reaction mixture was stirred for 6 h at RT then diluted with EtOAc (10 ml) and water (10 ml). The organic layer was separated and washed with water (5 ml), brine (5 ml), dried (Na2SO4), filtered and evaporated at reduced pressure to give the title compound as yellow oil (0.150 g, 41.6 %). The crude compound was taken on to the next step without further purification. LCMS data: Calculated MH+ (387); Found 100% (MH+) m/z 387, Rt = 5.78 min. 1H NMR (250 MHz, CHLOROFORM-J) delta ppm 1.38 - 2.15 (21 H, m) 2.47 - 2.81 (5 H, m) 3.63 (2 H, t, J=5.86 Hz) 4.40 (2 H, s) 4.97 (1 H, br. s.) 6.47 (1 H, d, J=8.38 Hz) 7.06 (1 H, d, J=8.38 Hz).
  • 5
  • [ 1036381-91-5 ]
  • 6-acetyl-1-methyl-3-[3-(1-methylpyrazol-4-yl)-8-isoquinolyl]-7,8-dihydro-5H-1,6-naphthyridin-2-one [ No CAS ]
  • 6
  • [ 1036381-91-5 ]
  • tert-butyl 3-bromo-1-methyl-2-oxo-7,8-dihydro-5H-1,6-naphthyridine-6-carboxylate [ No CAS ]
  • 7
  • [ 1036381-91-5 ]
  • 6-acetyl-3-bromo-1-methyl-7,8-dihydro-5H-1,6-naphthyridin-2-one [ No CAS ]
  • 8
  • [ 1036381-91-5 ]
  • C9H11BrN2O [ No CAS ]
  • 9
  • [ 1036381-91-5 ]
  • [ 24424-99-5 ]
  • [ 1036381-92-6 ]
YieldReaction ConditionsOperation in experiment
63% To a solution of <strong>[1036381-91-5]tert-butyl 2-oxo-1,5,7,8-tetrahydro-1,6-naphthyridine-6-carboxylate</strong>(275 mg,1.10 mmol)in acetic acid(2.2 mL)at 0 C was added bromine(67.7 J.L,1.32 mmol)portionwise. The mixture was stirred at room temperature for 3 h,then concentrated underreduced pressure. The resulting residue was dissolved in chloroform(4 mL)and water(2.0 mL).To the solution was added Boc20(3H2 mg,1.43 mmol)and K2C03(304 mg,2.20 mmol). Themixture was stirred for 14 h at room temperature. The resulting precipitate was filtered,washed with diethyl ether,and dried under reduced pressure to give the first batch of the title compound.The mother liquor was poured into a separatory funnel,the organic later was separated,driedover Na2S04 and concentrated under reduced pressure. The resulting solid was washed withdiethyl ether,and then dried under reduced pressure to give the second batch of the titlecompound(228 mg total,63%)that required no further purification. 1H NMR(400 MHz,CDCl3,16 I 17 H)8 7.59(s,1H),4.32(s,2H),3.67(t,J = 5.8 Hz,2H),2.74(t,J = 5.8 Hz,2H),1.48(s,9H).
  • 10
  • [ 1036381-91-5 ]
  • [ 1190440-43-7 ]
  • 11
  • [ 1036381-91-5 ]
  • [ 1190440-44-8 ]
  • 12
  • [ 1036381-91-5 ]
  • 2-[(1-cyclobutylpiperidin-4-yl)oxy]-5,6,7,8-tetrahydro-1,6-naphthyridine trifluoroacetate [ No CAS ]
 

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