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Chemical Structure| 40318-15-8 Chemical Structure| 40318-15-8
Chemical Structure| 40318-15-8

Methyl 4-methyl-1H-pyrrole-3-carboxylate

CAS No.: 40318-15-8

4.5 *For Research Use Only !

Cat. No.: A507623 Purity: 95%

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Product Details of [ 40318-15-8 ]

CAS No. :40318-15-8
Formula : C7H9NO2
M.W : 139.15
SMILES Code : O=C(C1=CNC=C1C)OC
MDL No. :MFCD10565693
InChI Key :CXMYWJRJTQUXQD-UHFFFAOYSA-N
Pubchem ID :15274278

Safety of [ 40318-15-8 ]

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

Calculated chemistry of [ 40318-15-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 5
Fraction Csp3 0.29
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 37.04
TPSA ?

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

42.09 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.68
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

0.93
Log Po/w (WLOGP)?

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

1.11
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.

0.37
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

1.68
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.15

Water Solubility

Log S (ESOL):?

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

-1.53
Solubility 4.14 mg/ml ; 0.0297 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.

-1.4
Solubility 5.54 mg/ml ; 0.0398 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

-2.04
Solubility 1.26 mg/ml ; 0.00906 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.

-6.49 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

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 [ 40318-15-8 ]

* 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 [ 40318-15-8 ]

[ 40318-15-8 ] Synthesis Path-Downstream   1~28

  • 2
  • [ 40318-15-8 ]
  • [ 79-22-1 ]
  • 4-Methyl-pyrrole-1,3-dicarboxylic acid dimethyl ester [ No CAS ]
  • 3
  • [ 623-43-8 ]
  • [ 38622-91-2 ]
  • [ 40318-15-8 ]
YieldReaction ConditionsOperation in experiment
25% With potassium tert-butylate; In tetrahydrofuran; at 20℃; for 3.5h; Reference Example 1 Methyl 4-methyl-1H-pyrrole-3-carboxylate To a suspension of potassium tert-butoxide (76.7 g) in tetrahydrofuran (900 mL) was added dropwise a solution of p-toluenesulfonylmethyl isocyanide (94.6 g) and methyl crotonate (48.5 g) in tetrahydrofuran (900 mL) over 30 min. The reaction mixture was stirred at room temperature for 3 hr, water was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent:hexane-ethyl acetate=4:1) to give the title compound as a white solid (yield 16.8 g, 25%). 1H-NMR (CDCl3) delta: 2.29 (3H, s), 3.80 (3H, s), 6.53-6.54 (1H, m), 7.36-7.38 (1H, m), 8.25 (1H, brs).
YieldReaction ConditionsOperation in experiment
25% With potassium tert-butylate; In tetrahydrofuran; at 10 - 35℃; for 1.5h; General procedure: Reference Example 39 Methyl 1H-pyrrole-3-carboxylate A solution (250 mL) of p-toluenesulfonylmethyl isocyanide (15.0 g) and methyl acrylate (6.92 mL) in tetrahydrofuran was added dropwise to a suspension (100 mL) of potassium tert-butoxide in tetrahydrofuran over 30 min. The reaction mixture was stirred at room temperature for 1 hr, and filtered through a glass filter filled with silica gel (diameter 8 cm, height 4 cm), and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=9:1?2:1) to give the title compound as a pale-yellow solid (yield 4.69 g, 49%). 1H-NMR (CDCl3)delta: 3.82 (3H, s), 6.15 (1H, m), 6.75 (1H, m), 7.43 (1H, m), 8.50 (1H, brs).
Reference Example 88 Methyl 4-methyl-1H-pyrrole-3-carboxylate Using p-toluenesulfonylmethyl isocyanide (94.6 g), methyl crotonate (48.5 g) and potassium tert-butoxide (76.7 g), a procedure as in Reference Example 39 was performed to give the title compound as a pale-yellow solid (yield 16.8 g, 25%). 1H-NMR (CDCl3)delta: 2.29 (3H, s), 3.80 (3H, s), 6.53-6.54 (1H, m), 7.36-7.38 (1H, m), 8.25 (1H, brs).
  • 5
  • (E)-3-(2-Bromo-allylamino)-acrylic acid methyl ester [ No CAS ]
  • [ 40318-15-8 ]
  • 6
  • [ 40318-15-8 ]
  • [ 76-02-8 ]
  • methyl 4-methyl-5-(2,2,2-trichloroacetyl)-1H-pyrrole-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With aluminum (III) chloride; In 1,2-dichloro-ethane; at -40 - 20℃; for 48h;Inert atmosphere; To a suspension of aluminum chloride (51.16 g, 384 mmol) in DCE (200 mL) was added trichloroacetyl chloride (43 mL, 384mmol) dropwise at -40 C under nitrogen atmosphere, followed by a solution of compound 1 (10.6 g, 76.7 mmol) in DCE (50 mL). The reaction mixture was gradually warmed to rt and stirred for 2 days. The mixture was poured into ice-water carefully and extracted with CH2Cl2. The combined organic layer was washed with 3 N HCl, brine, dried over anhydrous Na2SO4, and filtered. The solvent was evaporated in vacuo to afford 2 (20.3 g, 94 %) as a dark oil which was used for next step without further purification.
  • 8
  • [ 40318-15-8 ]
  • 4-[(3-Hydroxyphenyl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid methyl ester [ No CAS ]
  • 11
  • [ 40318-15-8 ]
  • 4-(4-bromo-3-hydroxy-phenylamino)-5-methyl-pyrrolo[2,1-<i>f</i>][1,2,4]triazine-6-carboxylic acid methyl ester [ No CAS ]
  • 12
  • [ 40318-15-8 ]
  • 4-(3-hydroxy-4-isopropyl-phenylamino)-5-methyl-pyrrolo[2,1-<i>f</i>][1,2,4]triazine-6-carboxylic acid methyl ester [ No CAS ]
  • 13
  • [ 40318-15-8 ]
  • 4-(4-ethyl-3-hydroxy-phenylamino)-5-methyl-pyrrolo[2,1-<i>f</i>][1,2,4]triazine-6-carboxylic acid methyl ester [ No CAS ]
  • 14
  • [ 40318-15-8 ]
  • 4-(3-hydroxy-4-propyl-phenylamino)-5-methyl-pyrrolo[2,1-<i>f</i>][1,2,4]triazine-6-carboxylic acid methyl ester [ No CAS ]
  • 15
  • [ 40318-15-8 ]
  • 4-(3-hydroxy-4-trifluoromethyl-phenylamino)-5-methyl-pyrrolo[2,1-<i>f</i>][1,2,4]triazine-6-carboxylic acid methyl ester [ No CAS ]
  • 16
  • [ 40318-15-8 ]
  • 4-(3-hydroxy-4-methyl-phenylamino)-5-methyl-pyrrolo[2,1-<i>f</i>][1,2,4]triazine-6-carboxylic acid (3-methoxy-propyl)-amide [ No CAS ]
  • 17
  • [ 40318-15-8 ]
  • 4-(3-hydroxy-4-methyl-phenylamino)-5-methyl-pyrrolo[2,1-<i>f</i>][1,2,4]triazine-6-carboxylic acid (3-[1,2,3]triazol-2-yl-propyl)-amide [ No CAS ]
  • 18
  • [ 40318-15-8 ]
  • 4-(3-hydroxy-4-methyl-phenylamino)-5-methyl-pyrrolo[2,1-<i>f</i>][1,2,4]triazine-6-carboxylic acid (3-pyrrolidin-1-yl-propyl)-amide [ No CAS ]
  • 19
  • [ 40318-15-8 ]
  • 4-(3-hydroxy-4-methyl-phenylamino)-5-methyl-pyrrolo[2,1-<i>f</i>][1,2,4]triazine-6-carboxylic acid (3-morpholin-4-yl-propyl)-amide [ No CAS ]
  • 23
  • [ 40318-15-8 ]
  • (1S,4S)-3-Methyl-6-(toluene-4-sulfonyl)-7-aza-bicyclo[2.2.1]hepta-2,5-diene-2,7-dicarboxylic acid dimethyl ester [ No CAS ]
  • 24
  • [ 40318-15-8 ]
  • (1S,4S)-3-Methyl-5-(toluene-4-sulfonyl)-7-aza-bicyclo[2.2.1]hepta-2,5-diene-2,7-dicarboxylic acid dimethyl ester [ No CAS ]
 

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Technical Information

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