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Chemical Structure| 2703-17-5 Chemical Structure| 2703-17-5
Chemical Structure| 2703-17-5

Methyl 1H-pyrrole-3-carboxylate

CAS No.: 2703-17-5

4.5 *For Research Use Only !

Cat. No.: A109547 Purity: 97%

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Product Details of [ 2703-17-5 ]

CAS No. :2703-17-5
Formula : C6H7NO2
M.W : 125.13
SMILES Code : COC(=O)C1=CNC=C1
MDL No. :MFCD00967074
InChI Key :WLBNVSIQCFHAQB-UHFFFAOYSA-N
Pubchem ID :12361759

Safety of [ 2703-17-5 ]

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

Calculated chemistry of [ 2703-17-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 5
Fraction Csp3 0.17
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 32.07
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.

1.41
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

0.56
Log Po/w (WLOGP)?

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

0.8
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.

0.02
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

1.24
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.81

Water Solubility

Log S (ESOL):?

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

-1.25
Solubility 7.07 mg/ml ; 0.0565 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.

-1.02
Solubility 12.1 mg/ml ; 0.0963 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

-1.64
Solubility 2.86 mg/ml ; 0.0229 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.

-6.67 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)

1.23

Application In Synthesis of [ 2703-17-5 ]

* 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.

  • Upstream synthesis route of [ 2703-17-5 ]

[ 2703-17-5 ] Synthesis Path-Upstream   1~1

  • 1
  • [ 2703-17-5 ]
  • [ 16420-39-6 ]
YieldReaction ConditionsOperation in experiment
62% With pyridine; N-Bromosuccinimide In tetrahydrofuran at -78℃; for 1 h; Reference Example 22 methyl 5-bromo-1H-pyrrole-3-carboxylate; A solution (30 mL) of methyl 1H-pyrrole-3-carboxylate (3.06 g) in tetrahydrofuran was cooled to -78° C., N-bromosuccinimide (4.38 g) and then pyridine (3 drops) were added, and the mixture was stirred at the same temperature for 1 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=5:1) to give the title compound as a pale-yellow solid (yield 3.08 g, 62percent). 1H-NMR (CDCl3) δ: 3.81 (3H, s), 6.58 (1H, m), 7.36 (1H, m), 8.60 (1H, brs).
49% With pyridine; N-Bromosuccinimide In tetrahydrofuran at -78 - -20℃; for 72 h; A solution of methyl 1H-pyrrole-3-carboxylate (4.48 g, 35.8 mmol) in THF (70 mL) was cooled to -78 °C, N-bromosuccinimide (6.30 g, 35.4 mmol) was added, pyridine (five drops) was added, and the mixture was left standing in a freezer (-20 °C) for 3 days. The reaction mixture was concentrated under reduced pressure. Water was added to the residue and the mixture was extracted with EtOAc. The extract was washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-EtOAc = 9/1-1/1) to give 12b (3.59 g, 49percent) as a pale-yellow solid: 1H NMR (CDCl3) δ 3.81 (3H, s), 6.58 (1H, m), 7.36 (1H, m), 8.60 (1H, br s).
49% With pyridine; N-Bromosuccinimide In tetrahydrofuran at -78 - -20℃; for 72 h; Reference Example 40
Methyl 5-bromo-1H-pyrrole-3-carboxylate
A solution (70 mL) of methyl 1H-pyrrole-3-carboxylate (4.48 g) in tetrahydrofuran was cooled to -78°C, N-bromosuccinimide (6.30 g) was added, pyridine (5 drops) was added, and the mixture was left standing in a freezer (-20°C) for 3 days.
The reaction mixture was concentrated under reduced pressure, water was added to the residue and the mixture was extracted with ethyl acetate.
The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.
The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=9:1→1:1) to give the title compound as a pale-yellow solid (yield 3.59 g, 49percent).
1H-NMR (CDCl3)δ: 3.81 (3H, s), 6.58 (1H, m), 7.36 (1H, m), 8.60 (1H, brs).
38 g With N-Bromosuccinimide In tetrahydrofuran at -78 - 20℃; (e) methyl 5-bromo-1 H-pyrrole-3-carboxylate To a solution of compound 71 d (40 g) in THF (60 ml) was added /V-bromosuccinimide (67.6 g) portion wise at -78°C. The reaction mixture was allowed to stir at room temperature overnight. The reaction mixture was concentrated. The crude product was purified by chromatography on silica gel, eluting with (Petrol: ethyl acetate=10:1 ) to give the desired compound. Yield: 38 g 1H NMR δ (ppm)(CHCI3-d): 8.625 (br, 1 H), 7.364 (dd, 1 H, Hz J2=2.8 Hz), 6.588 (dd, 1 H, Hz J2=2.4 Hz), 3.808 (s, 3H).

References: [1] Patent: US2007/60623, 2007, A1, . Location in patent: Page/Page column 23.
[2] Patent: WO2006/36024, 2006, A1, . Location in patent: Page/Page column 116; 286.
[3] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 12, p. 3925 - 3938.
[4] Patent: EP2336107, 2015, B1, . Location in patent: Paragraph 0214.
[5] Patent: EP1803709, 2007, A1, .
[6] Patent: WO2013/41458, 2013, A1, . Location in patent: Page/Page column 92; 93.
 

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