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Chemical Structure| 198821-79-3 Chemical Structure| 198821-79-3

Structure of 198821-79-3

Chemical Structure| 198821-79-3

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Product Details of [ 198821-79-3 ]

CAS No. :198821-79-3
Formula : C10H10N2O2
M.W : 190.20
SMILES Code : NC1=CC=C(C2=CN=CO2)C(OC)=C1
MDL No. :MFCD03844645
InChI Key :KYCMMXMEXWSPCV-UHFFFAOYSA-N
Pubchem ID :15462732

Safety of [ 198821-79-3 ]

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

Computational Chemistry of [ 198821-79-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 11
Fraction Csp3 0.1
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 52.84
TPSA ?

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

61.28 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.8
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

1.29
Log Po/w (WLOGP)?

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

1.94
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.

0.16
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

1.67
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.

-2.28
Solubility 0.995 mg/ml ; 0.00523 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.

-2.18
Solubility 1.27 mg/ml ; 0.00666 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

-3.53
Solubility 0.0565 mg/ml ; 0.000297 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

Yes
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

Yes
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.54 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

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<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)

2.37

Application In Synthesis of [ 198821-79-3 ]

* 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 [ 198821-79-3 ]

[ 198821-79-3 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 939-57-1 ]
  • [ 198821-79-3 ]
  • <i>N</i>-(3-methoxy-4-oxazol-5-yl-phenyl)-3-<i>o</i>-tolyl-acrylamide [ No CAS ]
  • 2
  • [ 1204-06-4 ]
  • [ 198821-79-3 ]
  • 3-(1<i>H</i>-indol-3-yl)-<i>N</i>-(3-methoxy-4-oxazol-5-yl-phenyl)-acrylamide [ No CAS ]
  • 3
  • [ 4565-31-5 ]
  • [ 198821-79-3 ]
  • C16H12N2O4S [ No CAS ]
YieldReaction ConditionsOperation in experiment
In ethanol; General procedure: The mixture of the compound 15 (190.2 mg, 1.0 mmol) and 2-thiophenecarboxaldehyde (123.4 mg, 1.1 mol) in anhydrous ethanol (3.0 mL) was stirred over night at room temperature or reflux temperature. The corresponding imine was reduced with solid sodium borohydride (75.7 mg, 2.0 mmol) which was added slowly, the mixture was further stirred over night at room temperature. An additional ethanol (2.0 mL) was added to the reaction vessel after which 10percent hydrochloric acid aqueous solution was added to quench excess sodium borohydride. The acidic mixture was basified with 25percent aqueous ammonia solution. The desired product was extracted with dichloromethane (3 20 mL) and the solution was dried over sodium sulphate anhydrous. The solvent was removed under reduced pressure and the residue was purified by flash chromatography on silica gel, eluting with a gradient of 40-60percent ethyl acetate in petroleum ether to give the title compound 17a1 [164.9 mg, 57.6percent (from 15)] as a white solid, mp 100-101 °C.
  • 4
  • [ 4565-31-5 ]
  • [ 198821-79-3 ]
  • 5-[3-methoxy-4-(5-oxazolyl)phenyl-amino]methyl}thiophene-2-carboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
54.6% Dissolve 3-methoxy-4-(oxazol-5-yl) aniline (190.2 mg, 1 mmol) in absolute ethanol (3 ml), add in 5-formyl-2-thiophene-carboxylic acid (1.1 mmol), stir at room temperature until the starting material 3-methoxy-4-(oxazol-5-yl) aniline disappears. Add a reducing agent (e.g. NaBH4, 2 mmol) at 0-10° C., then warm at ambient temperature until the disappearance of the intermediate. Dissolve the mixture under heating with ethanol, filter, and evaporate part of the solvent, let stand the mixture to obtain a yellow solid product 7, yield: 54.6percent. 1H NMR (DMSO-d6, delta) 3.82 (s, 3H, -OCH3), 4.39 (br, 1H, -NH), 4.40 (s, 2H, -CH2-), 6.32 (d, J=8.5 Hz, 1H, 6-Ph), 6.39 (s, 1H, 2-Ph), 6.85 (d, J=3 Hz, 1H, 3-Th); 7.03 (d, J=3.5 Hz, 1H, 4-Th), 7.18 (s, 1H, 4-Ox), 7.37 (d, J=8.5 Hz, 1H, 5-Ph); 8.21 (s, 1H, 2-Ox).
  • 5
  • [ 20426-80-6 ]
  • [ 198821-79-3 ]
  • N-(3-methoxy-4-(oxazol-5-yl)phenyl)chromane-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
44% With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃; for 12h; To a stirred solution of 3-methoxy-4- (oxazol-5-yl) aniline (75 mg, 0.395 mmol) and 3, 4-dihydro-2H-l-benzopyran-4- carboxylic acid (105.3 mg, 0.592 mmol) in DMF (3 mL) were added DIPEA (0.15 mL) and HATU (226 mg, 0.592 mmol) at room temperature and the reaction was stirred for 12 h at rt. After completion of the reaction, the reaction mixture was purified by preparative HPLC to yield N-(3-methoxy-4- (oxazol-5-yl) phenyl) chromane-4-carboxamide (60.07 mg, 44%). Analytical HPLC Method A. Rt: 1.42 min; MS: 351.2 (M+H) .
44% With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃; for 16h; To a stirred solution of 3-methoxy-4-(oxazol-5-yl)aniline (75 mg, 0.395 mmol) and 3,4-dihydro-2H-1-benzopyran-4- carboxylic acid (105.3 mg, 0.592 mmol) in DMF (3 mL) were added DIPEA (0.15 mL) and HATU (226 mg, 0.592 mmol) at room temperature and the reaction was stirred for 12 h at room temperature. After completion of the reaction, the reaction mixture was purified by preparative HPLC to yield N-(3-methoxy-4-(oxazol-5-yl)phenyl)chromane-4-carboxamide (60.07 mg, 44%). Analytical HPLC Method A. Rt: 1.42 min; MS: 351.2 (M+H).
  • 6
  • [ 182570-26-9 ]
  • [ 198821-79-3 ]
  • 6-methoxy-N-(3-methoxy-4-(oxazol-5-yl)phenyl)chromane-3-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
48% With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃; for 12h; To a stirred solution of 3-methoxy-4- (oxazol-5-yl) aniline (75 mg, 0.395 mmol) and 6-methoxy-3, 4-dihydro-2H-l- benzopyran-3-carboxylic acid (123.1 mg, 0.592 mmol) in DMF (3 ioL) were added DIPEA (0.15 mL) and HATU (226 mg, 0.592 mmol) at room temperature and the reaction was stirred for 12 h at rt. After completion of the reaction, the reaction mixture was purified by preparative HPLC to yield 6-methoxy-N- (3-methoxy-4- (oxazol-5-yl) phenyl) chromane-3- carboxamide (72.3 mg, 48%). Analytical HPLC Method A. Rt: 1.55 min; MS: 381.2 (M+H) .
48% With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃; for 12h; To a stirred solution of 3-methoxy-4-(oxazol-5-yl)aniline (75 mg, 0.395 mmol) and 6-methoxy-3,4-dihydro-2H-1- benzopyran-3-carboxylic acid (123.1 mg, 0.592 mmol) in DMF (3 mL) were added DIPEA (0.15 mL) and HATU (226 mg, 0.592 mmol) at room temperature and the reaction was stirred for 12 h at room temperature. After completion of the reaction, the reaction mixture was purified by preparative HPLC to yield 6-methoxy-N-(3-methoxy-4- (oxazol-5-yl)phenyl)chromane-3-carboxamide (72.3 mg, 48%). Analytical HPLC Method A. Rt: 1.55 min; MS: 381.2 (M+H).
 

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Technical Information

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