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Chemical Structure| 36692-49-6 Chemical Structure| 36692-49-6
Chemical Structure| 36692-49-6

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Methyl 3,4-diaminobenzoate

CAS No.: 36692-49-6

4.5 *For Research Use Only !

Cat. No.: A254289 Purity: 97%

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Product Details of [ 36692-49-6 ]

CAS No. :36692-49-6
Formula : C8H10N2O2
M.W : 166.18
SMILES Code : C1=C(C(OC)=O)C=CC(=C1N)N
MDL No. :MFCD00017098
InChI Key :IOPLHGOSNCJOOO-UHFFFAOYSA-N
Pubchem ID :135524

Safety of [ 36692-49-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P301+P312-P302+P352-P304+P340-P305+P351+P338

Calculated chemistry of [ 36692-49-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 2.0
Molar Refractivity 46.53
TPSA ?

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

78.34 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.16
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

0.46
Log Po/w (WLOGP)?

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

0.65
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.

0.74
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

0.26
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.65

Water Solubility

Log S (ESOL):?

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

-1.4
Solubility 6.64 mg/ml ; 0.04 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.

-1.67
Solubility 3.52 mg/ml ; 0.0212 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

-1.75
Solubility 2.97 mg/ml ; 0.0179 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.

-6.99 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)

1.32

Application In Synthesis of [ 36692-49-6 ]

* 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 [ 36692-49-6 ]

[ 36692-49-6 ] Synthesis Path-Downstream   1~10

  • 1
  • [ 36692-49-6 ]
  • [ 109012-24-0 ]
  • [ 585525-12-8 ]
  • 2
  • [ 36692-49-6 ]
  • [ 181765-85-5 ]
  • [ 755026-35-8 ]
YieldReaction ConditionsOperation in experiment
68% With potassium carbonate;copper; In chlorobenzene; for 20h;Heating / reflux; A mixture of <strong>[181765-85-5]methyl 4-chloro-2-iodobenzoate</strong> (0.593g, 2 mmol), methyl 3,4- diaminobenzoate (0.332g, 2 mmol), copper (0.126g, 2 MMOL), and K2CO3 (0.276g, 2 mmol) in chlorobenzene (40 mL) was heated to reflux for 20 hours, cooled to room temperature, diluted with ethyl acetate, and filtered through diatomaceous earth (ELITE). The solution was washed with water and brine, dried (MGS04), filtered, and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel with 7: 3 hexanes/ethyl acetate to provide 0.453g (68 %) of the desired product. MS (DCI) m/e 334 (M+H) +, 352 (M+NH4) + ; 1H NMR (300 MHz, DMSO-D6) # 8.99 (s, 1H), 7.89 (d, J = 8.5 Hz, 1 H), 7.47 (d, J = 1.0 Hz, 1H), 7.21 (m, 2H), 6.80 (dd, J = 8.5, 2.0 Hz, 1H), 6.65 (d, J = 2.1 Hz, 1H), 5.30 (s, 2H), 3.86 (s, 3H), 3.82 (s, 3H).
With copper; potassium carbonate; In chlorobenzene; for 18h;Reflux; Example 39Amethyl 2-(2-amino-4-(methoxycarbonyl)phenylamino)-4-chlorobenzoate To a solution of methyl-3,4-diaminobenzoate (2.8 g, 16.86 mmol, Alfa Aesar Chemical Company) in chlorobenzene (125 ml) was added Example 3A (5.0 g, 16.86 2345 mmol), K2CO3 (2.5 g, 17.71 mmol), and Cu (1.1 g, 16.86 mmol). The resulting mixture was heated at reflux over 18 hours. While hot, the mixture was filtered through a thin layer of diatomaceous earth and the cake washed with dichloromethane. The filtrate was concentrated and the crude product purified by flash chromatography on silica gel, eluting with a 10% - 100% CH2CI2 / hexanes gradient to yield the title compound. MS 2350 ESI(+) /M/Z 334.9 [M+H]+.
  • 3
  • [ 36692-49-6 ]
  • [ 107819-90-9 ]
  • [ 1420352-40-4 ]
YieldReaction ConditionsOperation in experiment
With camphor-10-sulfonic acid; In ethanol; water; at 20℃; for 3h;Heating / reflux; 2d 2-tert-butoxycarbonylamino-1H-benzimidazole-5-carboxylic acid Methyl 3,4-diaminobenzoate (7.0 g, 1 equivalent), <strong>[107819-90-9]1,3-bis(tert-butoxycarbonyl)-2-methyl-2-thiopseudourea</strong> (19.6 g, 1.6 equivalents) and camphorsulfonic acid (200 mg, cat.) are heated at reflux in ethanol (200 ml) for 3 h. The mixture is allowed to cool to r.t., then the solid is filtered, washed with ethanol, and dried to afford the intermediate methyl ester (8.2 g).
  • 4
  • [ 53911-68-5 ]
  • [ 36692-49-6 ]
  • [ 1221961-98-3 ]
  • 5
  • [ 53911-68-5 ]
  • [ 36692-49-6 ]
  • C19H19ClN2O5 [ No CAS ]
  • C19H19ClN2O5 [ No CAS ]
  • 6
  • [ 53911-68-5 ]
  • [ 36692-49-6 ]
  • [ 1221961-95-0 ]
  • 7
  • [ 36692-49-6 ]
  • [ 181765-85-5 ]
  • [ 1372589-50-8 ]
YieldReaction ConditionsOperation in experiment
With copper; potassium carbonate; In chlorobenzene; at 135℃; Example 3Bmethyl 2-(2-amino-5-(methoxycarbonyl)phenylamino)-4-chlorobenzoate Example 3 A (3.0 g, 10.12 mmol), methyl-3,4-diaminobenzoate (3.39 g, 10.12 mmol), 2C03 (1.47 g, 10.63 mmol), Cu (0.648 g, 10.12 mmol) and chlorobenzene ( 100 1 735 ml) were mixed. The reaction mixture was heated to reflux ( 135C) overnight then filtered hot through a thin layer of diatomaceous earth. The flask was rinsed and the cake was washed with CH2CI2 (100 ml). The filtrate was washed with water, dried (Na^SC^), filtered and concentrated. The crude product was purified by column chromatography with an Analogix SF-150 g Si column using 90: 10 CH2CI2: hexanes (25 minutes) then 1740 100% CH2CI2 to yield the title compound. MS ESI(+) m/z 334.9 [M+H]+
  • 8
  • [ 36692-49-6 ]
  • [ 1368310-81-9 ]
  • 9
  • [ 4845-50-5 ]
  • [ 36692-49-6 ]
  • [ 23088-23-5 ]
YieldReaction ConditionsOperation in experiment
96.7% In N,N-dimethyl-formamide; at 90.0℃; for 8.0h; Take a 100ml single-mouth bottle,Add 3,4-diaminobenzoic acid methyl ester (2) 3.32 g (0.02 mol),And added 30 ml of N,N-dimethylformamide, and dissolved by stirring.Then, [1,4]dioxane-2,3-diol (a) 3.6 g (0.03 mol) was added.Stir at 90 C for 8 hours.Then extracted, washed,Drying to give methyl quinoxaline-6-carboxylate (3)3.64 g, yield 96.7%.
  • 10
  • [ 131543-46-9 ]
  • [ 36692-49-6 ]
  • [ 23088-23-5 ]
 

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