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Structure of 129075-49-6

Chemical Structure| 129075-49-6

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Product Details of [ 129075-49-6 ]

CAS No. :129075-49-6
Formula : C10H11NO2
M.W : 177.20
SMILES Code : O=C1NCCC2=C1C=CC=C2OC
MDL No. :MFCD07196047
InChI Key :OESOLVOZJGIVMY-UHFFFAOYSA-N
Pubchem ID :7385098

Safety of [ 129075-49-6 ]

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

Computational Chemistry of [ 129075-49-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 6
Fraction Csp3 0.3
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 52.7
TPSA ?

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

38.33 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.84
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

1.2
Log Po/w (WLOGP)?

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

0.6
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.

1.14
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

2.07
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.37

Water Solubility

Log S (ESOL):?

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

-1.97
Solubility 1.9 mg/ml ; 0.0107 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.

-1.6
Solubility 4.44 mg/ml ; 0.025 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

-3.29
Solubility 0.0903 mg/ml ; 0.000509 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.

-6.53 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)

1.63

Application In Synthesis of [ 129075-49-6 ]

* 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 [ 129075-49-6 ]

[ 129075-49-6 ] Synthesis Path-Downstream   1~16

  • 1
  • [ 85834-35-1 ]
  • [ 129075-49-6 ]
  • 2-{2-[4-(4-chloro-phenyl)-piperazin-1-yl]-ethyl}-5-methoxy-3,4-dihydro-2<i>H</i>-isoquinolin-1-one [ No CAS ]
  • 3
  • [ 56469-02-4 ]
  • [ 333-27-7 ]
  • [ 129075-49-6 ]
  • 4
  • [ 103205-24-9 ]
  • [ 129075-49-6 ]
  • 5
  • C11H13NO4S [ No CAS ]
  • [ 30557-06-3 ]
  • [ 129075-49-6 ]
  • 6
  • 4-methoxy-indan-1-one oxime [ No CAS ]
  • [ 129075-49-6 ]
  • 8
  • [ 56469-02-4 ]
  • [ 129075-49-6 ]
YieldReaction ConditionsOperation in experiment
5.3 g (89%) With dimethyl sulfate; In methanol; sodium hydroxide; water; EXAMPLE V 3,4-Dihydro-5-methoxy-1(2H)-isoquinolinone To a refluxing solution of 5.5 g (33.7 mmol) of 3,4-dihydro-5-hydroxy-1(2H)-isoquinolinone in 35 ml of 2N NaOH and 70 ml of methanol was added 4 ml of dimethyl sulfate. At two-hour intervals additional amounts of NaOH and dimethyl sulfate were added and the reaction was heated under reflux conditions overnight. The mixture was concentrated, diluted with 300 ml of water, and acidified (pH 2-3) with concentrated sulfuric acid. The solid which formed was collected and dried to give 5.3 g (89%) of material sufficiently pure for the next step. An analytical sample was obtained by recrystallization from acetone; mp 147-149.
  • 9
  • [ 56469-02-4 ]
  • [ 74-88-4 ]
  • [ 129075-49-6 ]
YieldReaction ConditionsOperation in experiment
Intermediate Q5-Methoxy-3,4-dihydro-2H-isoquinolin-1 -oneTo a stirring solution of 5-hydroxy-3,4-dihydroisoquinolin-1(2H)-one (200 mg, 1.226 mmol) in DMF (8 ml) was added Cs2C03 (599 mg, 1.839 mmol). The reation mixture was left to stir for 20 minutes at 50 C and then treated with methyl iodide (0.115 ml, 1.839 mmol). After stirring at 50 C for 30 min, the mixture was diluted with EtOAc water. The organic portion was separated and washed with water, brine, dried (MgS04) and concentrated in vacuo to afford the title compound as a pale yellow solid; LC-MS Rt =1.08 mins; MS m/z 178.1 [M+H]+; Method 2minLC_v002.
  • 11
  • [ 40731-98-4 ]
  • [ 129075-49-6 ]
  • 12
  • [ 129075-49-6 ]
  • 2-(3-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)propyl)-5-methoxy-3,4-dihydroisoquinolin-1(2H)-one [ No CAS ]
  • 13
  • [ 109-70-6 ]
  • [ 129075-49-6 ]
  • 2-(3-chloropropyl)-5-methoxy-3,4-dihydroisoquinolin-1(2H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
58% General procedure: To a suspension of NaH (0.11g, 4.5mmol) in DMF (10 mL), a solution in DMF (5 mL) of the appropriate 3,4-dihydroisoquinolin-1-one (1.8 mmol), was added in a dropwise manner, at 0 C under a stream of N2. After 15min, 1-bromo-3-chloropropane was added in a dropwise manner and the mixture was allowed to warm to room temperature and was kept under stirring for 30 min. After cooling to 0 C H2O was added and the solvent was removed under reduced pressure. The residue was taken up with water and extracted with AcOEt (3×10 mL). The organic layers were collected, dried over Na2SO4 and evaporated under reduced pressure. The crude residue was purified by column chromatography with CH2Cl2/AcOEt (1:1) as eluent.
  • 14
  • [ 13336-31-7 ]
  • [ 129075-49-6 ]
YieldReaction ConditionsOperation in experiment
42% With hydrogenchloride; sodium azide; In water; at 0 - 20℃; General procedure: To a solution of the appropriate indan-1-one (1.5 mmol) in 37% HCl (5 mL) at 0 C NaN3 (0.2 g, 3.0 mmol) was cautiously added. The mixture was stirred overnight at room temperature. The mixture was poured into ice and made basic with Na2CO3. The aqueous layer was extracted with ethyl acetate (3 × 10 mL). The collected organic phases were dried over Na2SO4 and concentrated under reduced pressure to give a crude residue which was purified by column chromatography with CH2Cl2/AcOEt (9:1) as eluent.
  • 15
  • [2-(2-methoxy-phenyl)-ethyl]-carbamic acid ethyl ester [ No CAS ]
  • [ 129075-49-6 ]
YieldReaction ConditionsOperation in experiment
12.8% With phosphorus pentoxide; trichlorophosphate; at 110℃; for 3h; Step 4: Preparation of Intermediate 5-Methoxy-3,4-dihydro-2H-isoquinolin-1-one (I-13d) Using the same procedure and workup as described in example 1, step 4, [2-(2-methoxy-phenyl)-ethyl]-carbamic acid ethyl ester (I-13c: 0.9 g, 0.0040 mmol) in POCl3 (5 mL) was reacted with P2O5 (1.19 g, 0.0084 mmol). The resulting mixture was stirred at 110 C. for 3 hours to afford the crude product. Purification by column chromatography on silica gel (1% methanol in CHCl3) afforded 90 mg of the product (12.8% yield). LCMS purity: 100%, m/z=178.1 (M+1)
  • 16
  • [ 129075-49-6 ]
  • [ 103030-70-2 ]
 

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Technical Information

Categories

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