16382-15-3|Ethyl 5-methylindole-2-carboxylate| Ambeed

CAS No. :	16382-15-3
Formula :	C₁₂H₁₃NO₂
M.W :	203.24
SMILES Code :	O=C(C(N1)=CC2=C1C=CC(C)=C2)OCC
MDL No. :	MFCD00022703
InChI Key :	KMVFKXFOPNKHEM-UHFFFAOYSA-N
Pubchem ID :	232919

Safety of [ 16382-15-3 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H317
Precautionary Statements:	P280

Computational Chemistry of [ 16382-15-3 ] Show Less

Physicochemical Properties

Num. heavy atoms	15
Num. arom. heavy atoms	9
Fraction Csp3	0.25
Num. rotatable bonds	3
Num. H-bond acceptors	2.0
Num. H-bond donors	1.0
Molar Refractivity	59.35
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	42.09 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.41
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	2.97
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.65
Log P_o/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.	1.95
Log P_o/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	3.19
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.63

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.22
Solubility	0.123 mg/ml ; 0.000606 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.	-3.52
Solubility	0.0618 mg/ml ; 0.000304 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	-4.16
Solubility	0.0142 mg/ml ; 0.0000697 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately 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.	-5.43 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	0.0
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)	1.88

Application In Synthesis of [ 16382-15-3 ]

* 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 [ 16382-15-3 ]

[ 16382-15-3 ] Synthesis Path-Downstream 1~54

1
[ 64-17-5 ]
[ 89314-29-4 ]
[ 16382-15-3 ]

References: [1]Journal of Biological Chemistry,1925,vol. 62,p. 507.

2
[ 91462-34-9 ]
[ 16382-15-3 ]

References: [1]Heterocycles,1984,vol. 22,p. 1211 - 1216.
[2]Justus Liebigs Annalen der Chemie,1887,vol. 239,p. 227.
[3]Gazzetta Chimica Italiana,1957,vol. 87,p. 949,953, 958.

3
[ 89-87-2 ]
[ 95-92-1 ]
[ 16382-15-3 ]

References: [1]Journal of the Chemical Society,1949,p. Spl. 231.

4
[ 16382-15-3 ]
[ 89-98-5 ]
[ 73725-20-9 ]

References: [1]Chemistry of Heterocyclic Compounds,1980,vol. 16,p. 373 - 376.
Khimiya Geterotsiklicheskikh Soedinenii,1980,vol. 16,p. 489 - 492.

5
[ 16382-15-3 ]
[ 97-00-7 ]
1-(2,4-Dinitro-phenyl)-5-methyl-1H-indole-2-carboxylic acid ethyl ester [ No CAS ]

References: [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1992,vol. 31,p. 551 - 554.

6
[ 16382-15-3 ]
[ 89-61-2 ]
1-(4-Chloro-2-nitro-phenyl)-5-methyl-1H-indole-2-carboxylic acid ethyl ester [ No CAS ]

References: [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1990,vol. 29,p. 1113 - 1117.

7
[ 16382-15-3 ]
[ 93704-67-7 ]

Yield	Reaction Conditions	Operation in experiment
98%	With N-Bromosuccinimide; In tetrahydrofuran; at 20℃; for 3.5h;	To a solution of S-methyl-lH-indole^-carboxylic acid ethyl ester, 3A (10.17 g, 50.03 mmol) in THF (100 mL) in a room temperature water bath was slowly added NBS (8.91 g, 50.06 mmol). The resulting solution was allowed to stir at room temperature for 3.5 h before water (800 mL) was added. The resulting mixture was allowed to stir at room temperature for 20 min and then filtered. The solid was washed with water (2 x 100 mL), dried in vacuo to provide the crude product 3B as a tan powder (13.8 g, 98percent yield). 1H NMR (500 MHz, CDC13): delta 8.91 (s, IH), 7.44 (q, J= 0.95 Hz 0.63 Hz, IH), 7.28 (d, J= 8.51 Hz, IH), 7.21 7.19 (dd, J= 1.58 Hz 8.51 Hz, IH), 4.46 (q, J= 6.94 Hz 7.25 Hz, 2H), 2.47 (s, 3H), 1.45 (t, J= 7.25 Hz, 3H).

References: [1]Patent: WO2009/32116,2009,A1 .Location in patent: Page/Page column 214.
[2]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1984,vol. 23,p. 930 - 933.

8
[ 16382-15-3 ]
[ 1463-64-5 ]

References: [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1986,vol. 25,p. 716 - 720.
[2]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1983,vol. 22,p. 571 - 576.

9
[ 16382-15-3 ]
[ 122-04-3 ]
5-Methyl-4-(4-nitro-benzoyl)-1H-indole-2-carboxylic acid ethyl ester [ No CAS ]
5-Methyl-7-(4-nitro-benzoyl)-1H-indole-2-carboxylic acid ethyl ester [ No CAS ]

References: [1]Chemistry of Heterocyclic Compounds,1993,vol. 29,p. 898 - 901.
Khimiya Geterotsiklicheskikh Soedinenii,1993,p. 1055 - 1059.

10
[ 16382-15-3 ]
[ 107-14-2 ]
[ 126718-05-6 ]

References: [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1989,vol. 28,p. 1065 - 1068.

11
[ 235759-00-9 ]
[ 16382-15-3 ]
ethyl 7-methanesulfonyloxy-5-methylindole-2-carboxylate [ No CAS ]

References: [1]Chemical and Pharmaceutical Bulletin,1999,vol. 47,p. 791 - 797.

Yield	Reaction Conditions	Operation in experiment
1%		Ethyl 5-methylindole-2-carboxylate in 1percent yield (2 steps), mp 157-158°; NMR delta(CD3SOCD3) 1.3 (t, 3H), 2.35 (s, 3H), 4.3 (q, 2H), 7.05 (m, 2H), 7.35 (m, 2H), 11.7 (bs, 1H); M/z (+) 203 (M+).
		B. 5-Methyl-1H-indole-2-carboxylic acid, ethyl ester The title A compound (2.095 g, 9.51 mmol, 1.0 eq) was dissolved in absolute ethanol (9.8 ml, 1M) and hydrochloric acid gas was bubbled through the reaction until it showed no starting material (45 minutes). The reaction solution was then concentrated, dissolved in ethyl acetate, and washed once with aqueous saturated sodium hydrogen carbonate. The organic phase was then dried over sodium sulfate, filtered through magnesium sulfate and concentrated. The residue was chromatographed on silica gel (60 g) eluding with toluene followed by chloroform:hexane (1:4) followed by ether:hexane (2:3) to give the title B compound (1.5187 g).
		b Ethyl 5-methylindole-2-carboxylate 130 g of P2 O5 are added to 111 ml of orthophosphoric acid. After cooling, 37 g of the compound from a) are added, and the mixture is heated to 80° C. After the reaction starts, the temperature rises to 130° C. The mixture is cooled and then poured into ice-water and extracted with ethyl acetate. The organic phase is washed with NaHCO3 (1N), H2 O and saturated NaCl solution, dried with Na2 SO4 and concentrated. The product is recrystallized from n-hexane/EtOAc. 11.7 g of product of melting point 158° C. are obtained.

14
[ 16382-15-3 ]
Br₂ [ No CAS ]
[ 93704-67-7 ]

References: [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1984,vol. 23,p. 1058 - 1063.

15
[ 16382-15-3 ]
3-Amino-7-methyl-5H-indolo[1,2-a]quinoxalin-6-one [ No CAS ]

References: [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1992,vol. 31,p. 551 - 554.

16
[ 16382-15-3 ]
[ 51698-84-1 ]