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Structure of 75844-40-5

Chemical Structure| 75844-40-5

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Product Details of [ 75844-40-5 ]

CAS No. :75844-40-5
Formula : C9H8N2O
M.W : 160.17
SMILES Code : O=C1NC=NC2=C1C=CC(C)=C2
MDL No. :MFCD00089490
InChI Key :APPHSAIPZPYEGB-UHFFFAOYSA-N
Pubchem ID :135452533

Safety of [ 75844-40-5 ]

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

Computational Chemistry of [ 75844-40-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 10
Fraction Csp3 0.11
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 47.33
TPSA ?

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

45.75 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.42
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

1.13
Log Po/w (WLOGP)?

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

1.23
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.

1.44
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

2.54
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.55

Water Solubility

Log S (ESOL):?

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

-2.16
Solubility 1.1 mg/ml ; 0.00689 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.

-1.68
Solubility 3.31 mg/ml ; 0.0207 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

-3.61
Solubility 0.0392 mg/ml ; 0.000245 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

No
Log Kp (skin permeation)?

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

-6.47 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)

1.42

Application In Synthesis of [ 75844-40-5 ]

* 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 [ 75844-40-5 ]

[ 75844-40-5 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 64-18-6 ]
  • [ 39549-79-6 ]
  • [ 75844-40-5 ]
YieldReaction ConditionsOperation in experiment
91% at 100℃; for 6h; 2-amino-4-mthylbenzamide (4.93 g, 32.8 mmol) obtained in above was added with formic acid (30 mL, 787.9 mmol), followed by stirring for 6 hours at 100°C. The reaction mixture was cooled to room temperature, concentrated under reduced pressure, and washed with water. The filtered solid was dried with warm wind in an oven (40°C) for 6 hours or more to obtain the title compound (4.79 g, 91percent). 1H-NMR Spectrum (300 MHz, DMSO-rftf): delta 8.06 (s, 1H), 8.00 (d, 1H), 7.47 (s, 1H), 7.34 (d, 1H), 2.45 (s, 3H) MS(ESI+, m/z): 161 [M+H]+
91% at 100℃; for 6h; <strong>[39549-79-6]2-amino-4-methylbenzamide</strong> (4.93 g, 32.8 mmol) obtained in <Step 1> above was added with formic acid (30 mL, 787.9 mmol), followed by stirring for 6 hours at 100° C. The reaction mixture was cooled to room temperature, concentrated under reduced pressure, and washed with water. The filtered solid was dried with warm wind in an oven (40° C.) for 6 hours or more to obtain the title compound (4.79 g, 91percent). 1H-NMR Spectrum (300 MHz, DMSO-d6): delta 8.06 (s, 1H), 8.00 (d, 1H), 7.47 (s, 1H), 7.34 (d, 1H), 2.45 (s, 3H) MS (ESI+, m/z): 161 [M+H]+
84% at 100℃; for 6h; A mixture of <strong>[39549-79-6]2-amino-4-methylbenzamide</strong> (20 g, 133 mmol) and formic acid (120 ml, 3129 mmol) was heated to 100 0C for 6 h. The reaction was cooled to RT and the volatiles were removed under reduced pressure. The residue was then washed carefully with aqueous saturated sodium bicarbonate and then with water. The tan solid was then dried in a vacuum oven at 45 0C overnight to give 7-methylquinazolin-4(3H)-one (18.00 g, 84percent yield). MS (ESI, pos. ion) m/z: 161 [M+H]+
Example 332; Preparation of 7-methyIquinazolin-4(3H)-oneA mixture of <strong>[39549-79-6]2-amino-4-methylbenzamide</strong> (20 g, 133 mmol)and formic acid (120 ml, 3129 mmol) was heated to 100 0C. After 6 hours, the reaction was cooled down to to RT and the volatiles were removed under reduced pressure. The residue was then washed carefully with aqueous saturated sodium bicarbonate and then with water. The tan solid <n="118"/>was then dried in a vacuum oven at 45 0C overnight to give 7-methylquinazolin-4(3H)- one. MS (M+H)+ 161.

  • 2
  • [ 39549-79-6 ]
  • [ 122-51-0 ]
  • [ 75844-40-5 ]
YieldReaction ConditionsOperation in experiment
1.1 g at 110℃; for 4h;Sealed tube; A suspension of <strong>[39549-79-6]2-amino-4-methylbenzamide</strong> (1.2 g, 8.0 mmol) in CH(OEt)3 (10 mL) was heated in a sealed tube at 110° C. for 4 h. Then the reaction was quenched with aq. NaHCO3 solution at rt and the precipitate obtained was filtered and dried. The solid mass was purified by column chromatography to afford 1.1 g of the title product. 1H NMR (300 MHz, DMSO-d6): delta 12.14 (br s, 1H), 8.05 (s, 1H), 8.00 (d, J=7.8 Hz, 1H), 7.47 (s, 1H), 7.34 (d, J=7.8 Hz, 1H), 2.45 (s, 3H).
  • 3
  • [ 39549-79-6 ]
  • [ 77287-34-4 ]
  • [ 75844-40-5 ]
YieldReaction ConditionsOperation in experiment
76% With ytterbium(III) triflate; In 1,3,5-trimethyl-benzene; at 165℃; for 6h;Inert atmosphere; General procedure: A mixture of 2-aminobenzamide (1, 4.0 mmol), carboxamide (2, 6.0 mmol), Yb(OTf)3 (0.20 mmol,5.0 molpercent), and mesitylene (5.0 mL) was placed in a 20-mL Pyrex flask equipped with a magnetic stirring bar and a reflux condenser under a flow of argon. The reaction was carried out at 120-165 oC (bath temp.) for 6 h with stirring. Then, the reaction mixture was cooled to room temperature, and analyzed by GLC, GC-MS (EI), and LC-MS (ESI). After evaporation of mesitylene under vacuum,the products (3) were isolated by recrystallization from MeOH/hexane and/or medium pressure column chromatography on silica gel (eluent: EtOAc/hexane = 50/50 ~ EtOAc 100percent. For 3j, eluent:MeOH/CHCl3 = 50/50). 1H NMR spectra were recorded at 400 MHz, and 13C NMR spectra wererecorded at 100 MHz in DMSO-d6. The analytical and spectral data of 3a-e,38 3f,39 3g,40 3h,41 and3j,42 were consistent with those reported previously. The product, 3i, was characterized below.
  • 4
  • [ 67-56-1 ]
  • [ 39549-79-6 ]
  • [ 75844-40-5 ]
YieldReaction ConditionsOperation in experiment
87% With [Cp*Ir(2,2'-bpyO)(H2O)]; caesium carbonate; at 130℃; for 2h;Inert atmosphere; Microwave irradiation; <strong>[39549-79-6]2-amino-4-methylbenzamide</strong> (75 mg, 0.5 mmol), [Cp * Ir (2,2'-bpyO) (H2O)](5.4 mg, 0.005 mmol, 1 molpercent),Cesium carbonate (49 mg, 0.15 mmol, 0.3 equiv.) And methanol (0.5 ml) were sequentially added to a dried 5 mL microwave reaction tube.The tube was nitrogen protected and placed in a single mode pressure microwave synthesizer (Discover CEM, USA). After the reaction mixture was reacted at 130 ° C for 2 hours, it was cooled to room temperature. Rotary evaporation to remove the solvent,Then, column chromatography (developing solvent: petroleum ether / ethyl acetate)The pure target compound was obtained in a yield of 87percent
  • 5
  • [ 39549-79-6 ]
  • [ 144-62-7 ]
  • [ 75844-40-5 ]
 

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Technical Information

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