65417-22-3|Methyl 2-methyl-1H-indole-3-carboxylate| Ambeed

CAS No. :	65417-22-3
Formula :	C₁₁H₁₁NO₂
M.W :	189.21
SMILES Code :	O=C(C1=C(C)NC2=C1C=CC=C2)OC
MDL No. :	MFCD00963961
InChI Key :	WQBPRTUBQKFRKZ-UHFFFAOYSA-N
Pubchem ID :	594174

Safety of [ 65417-22-3 ]

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

Computational Chemistry of [ 65417-22-3 ] Show Less

Physicochemical Properties

Num. heavy atoms	14
Num. arom. heavy atoms	9
Fraction Csp3	0.18
Num. rotatable bonds	2
Num. H-bond acceptors	2.0
Num. H-bond donors	1.0
Molar Refractivity	54.54
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.	2.03
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	2.3
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.26
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.	1.67
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	2.83
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.22

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.81
Solubility	0.296 mg/ml ; 0.00156 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.	-2.82
Solubility	0.285 mg/ml ; 0.00151 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	-3.75
Solubility	0.0337 mg/ml ; 0.000178 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.	-5.82 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)	1.6

Application In Synthesis of [ 65417-22-3 ]

* 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 [ 65417-22-3 ]

[ 65417-22-3 ] Synthesis Path-Downstream 1~55

1
[ 186581-53-3 ]
[ 63176-44-3 ]
[ 65417-22-3 ]

References: [1]Journal of the Chemical Society,1951,p. 3235,3238.

2
[ 872270-34-3 ]
[ 65417-22-3 ]

References: [1]Journal of the Chemical Society,1951,p. 3235,3238.

3
[ 95-20-5 ]
[ 687-74-1 ]
[ 65417-22-3 ]
2-methyl-3-isopropylideneindolenine tetrafluoroborate [ No CAS ]

References: [1]Monatshefte fur Chemie,1986,vol. 117,p. 375 - 384.
[2]Monatshefte fur Chemie,1986,vol. 117,p. 375 - 384.

4
[ 68870-52-0 ]
[ 65417-22-3 ]

References: [1]Journal of the Chemical Society. Perkin transactions I,1987,p. 413 - 422.
[2]Journal of the Chemical Society. Chemical communications,1986,p. 399 - 401.

5
[ 128942-80-3 ]
[ 65417-22-3 ]

References: [1]Synthesis,1990,p. 215 - 218.

6
[ 65417-20-1 ]
[ 75-65-0 ]
[ 65417-22-3 ]
[ 81564-26-3 ]
[ 81564-27-4 ]

References: [1]Chemical and pharmaceutical bulletin,1982,vol. 30,p. 74 - 86.
[2]Chemical and pharmaceutical bulletin,1982,vol. 30,p. 74 - 86.
[3]Chemical and pharmaceutical bulletin,1982,vol. 30,p. 74 - 86.
[4]Chemical and pharmaceutical bulletin,1982,vol. 30,p. 74 - 86.

7
[ 65417-20-1 ]
[ 65417-22-3 ]
[ 55625-40-6 ]
[ 74960-50-2 ]

References: [1]Chemical and Pharmaceutical Bulletin,1980,vol. 28,p. 1157 - 1171.

8
[ 107097-19-8 ]
[ 65417-22-3 ]

References: [1]Tetrahedron,1986,vol. 42,p. 2985 - 2992.

9
[ 74960-50-2 ]
[ 65417-22-3 ]

References: [1]Chemical and Pharmaceutical Bulletin,1980,vol. 28,p. 1157 - 1171.

10
[ 65417-27-8 ]
[ 65417-22-3 ]
[ 62542-43-2 ]
[ 74960-64-8 ]

References: [1]Chemical and Pharmaceutical Bulletin,1980,vol. 28,p. 1157 - 1171.
[2]Chemical and Pharmaceutical Bulletin,1980,vol. 28,p. 1157 - 1171.

11
[ 88344-49-4 ]
[ 65417-22-3 ]
[ 58416-48-1 ]
[ 88342-87-4 ]
[ 148302-66-3 ]

References: [1]Australian Journal of Chemistry,1983,vol. 36,p. 1419 - 1430.

12
[ 88344-49-4 ]
[ 65417-22-3 ]
[ 58416-48-1 ]
[ 88342-87-4 ]
[ 148302-66-3 ]
[ 88344-66-5 ]

References: [1]Australian Journal of Chemistry,1983,vol. 36,p. 1419 - 1430.

13
[ 88344-49-4 ]
[ 65417-22-3 ]
[ 58416-48-1 ]
[ 88342-87-4 ]
[ 88344-66-5 ]

References: [1]Australian Journal of Chemistry,1983,vol. 36,p. 1419 - 1430.
[2]Australian Journal of Chemistry,1983,vol. 36,p. 1419 - 1430.

14
[ 88344-49-4 ]
[ 65417-22-3 ]
[ 58416-48-1 ]
[ 88342-87-4 ]
[ 88342-83-0 ]

References: [1]Australian Journal of Chemistry,1983,vol. 36,p. 1419 - 1430.

15
[ 68870-53-1 ]
[ 65417-22-3 ]
[ 104711-29-7 ]

References: [1]Journal of the Chemical Society. Perkin transactions I,1987,p. 413 - 422.
[2]Journal of the Chemical Society. Chemical communications,1986,p. 399 - 401.

16
[ 65417-22-3 ]
[ 98-09-9 ]
[ 154953-37-4 ]

References: [1]Journal of Chemical Research, Miniprint,1993,p. 2411 - 2428.

18
[ 1694-31-1 ]
[ 615-43-0 ]
[ 124-41-4 ]
[ 65417-22-3 ]

References: [1]Journal of Organic Chemistry,2003,vol. 68,p. 6011 - 6019.

19
[ 1694-31-1 ]
[ 124-41-4 ]
[ 615-36-1 ]
[ 65417-22-3 ]

References: [1]Journal of Organic Chemistry,2003,vol. 68,p. 6011 - 6019.

20
[ 615-43-0 ]
[ 105-45-3 ]
[ 65417-22-3 ]

Yield	Reaction Conditions	Operation in experiment
87%	With copper(l) iodide; 1H-tetrazol-1-ylacetic acid; caesium carbonate; In dimethyl sulfoxide; at 80℃; for 12h;Sealed tube;	General procedure: To a 10mL sealed tube was added CuI (0.05mmol), L4 (0.1mmol), ortho-iodo/bromoaniline (0.5mmol), beta-keto ester/beta-diketone (3.0mmol), Cs2CO3 (1.0mmol), and DMSO (1mL). The reaction mixture was reacted at 80C in a preheated oil bath for 12h (for ortho-iodoanilines) or 36h (for ortho-bromoanilines). The reaction mixture was cooled to room temperature and extracted with ethyl acetate (3×20mL). The combined organic phases were washed with water and brine, dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by flash column chromatograph on silica gel (ethyl acetate/petroleum ether as the eluent) to afford the target products 3a-3s.
85%	With cetyltrimethylammonim bromide; potassium carbonate; In water; at 50℃; for 3h;Green chemistry;Catalytic behavior;	A mixture of the appropriate 1,3-dicarbonyl compound 3 (1.1equiv), 2-iodoaniline (1 equiv), CTAB (10 mol%), K2CO3 (1equiv), and magnetic catalyst (20 mg) in H2O (4 mL) was stirredat 50 C for 3 h then cooled to r.t. The catalyst was removed byusing an external magnet, and the solution was extracted withEtOAc (3 × 10 mL). The extracts were dried (MgSO4), filtered,and concentrated under vacuum to give a crude product thatwas purified by column chromatography.Methyl 2-Methyl-1H-indole-3-carboxylate (4a)Beige solid; yield: 160 mg (85%); mp 164-166 C. IR (KBr):3016, 1690, 1449, 1209, 10905 cm-1. 1H NMR (400 MHz, CDCl3):delta = 2.72 (s, 3 H), 3.93 (s, 3 H), 7.16-7.30 (m, 3 H), 8.08 (d, J= 7.7Hz, 1 H), 8.67 (br s, 1 H). 13C NMR (100 MHz, CDCl3): delta = 14.2,50.8, 104.3, 110.4, 121.2, 121.7, 122.3, 127.2, 134.5, 144.2,166.7.

References: [1]Tetrahedron,2016,vol. 72,p. 653 - 657.
[2]Synlett,2016,vol. 27,p. 1665 - 1668.
[3]Synlett,2011,p. 623 - 626.
[4]European Journal of Organic Chemistry,2007,p. 3977 - 3980.
[5]Research on Chemical Intermediates,2014,vol. 40,p. 2157 - 2164.

21
[ 65417-22-3 ]
methyl 2-formyl-1-(phenylsulfonyl)-1H-indole-3-carboxylate [ No CAS ]

References: [1]Journal of Chemical Research, Miniprint,1993,p. 2411 - 2428.

22
[ 65417-22-3 ]
[ 154953-45-4 ]

References: [1]Journal of Chemical Research, Miniprint,1993,p. 2411 - 2428.

23
[ 88344-65-4 ]
[ 65417-22-3 ]

References: [1]Australian Journal of Chemistry,1983,vol. 36,p. 1419 - 1430.

24
[ 58416-48-1 ]
[ 65417-22-3 ]

References: [1]Australian Journal of Chemistry,1983,vol. 36,p. 1419 - 1430.

25
[ 95-14-7 ]
[ 65417-22-3 ]

References: [1]Tetrahedron,1986,vol. 42,p. 2985 - 2992.

26
[ 21050-95-3 ]
[ 65417-22-3 ]

References: [1]Tetrahedron,1986,vol. 42,p. 2985 - 2992.

27
[ 23326-27-4 ]
[ 65417-22-3 ]

References: [1]Tetrahedron,1986,vol. 42,p. 2985 - 2992.

28
[ 615-43-0 ]
[ 65417-22-3 ]

References: [1]Synthesis,1990,p. 215 - 218.

29
[ 105-45-3 ]
[ 65417-22-3 ]

References: [1]Synthesis,1990,p. 215 - 218.
[2]ACS Catalysis,2015,vol. 5,p. 4751 - 4755.
[3]Organic and Biomolecular Chemistry,2017,vol. 15,p. 8054 - 8058.
[4]Organic Letters,2020,vol. 22,p. 3397 - 3401.

30
[ 1082470-52-7 ]
[ 65417-22-3 ]
[ 1082470-54-9 ]

References: [1]Angewandte Chemie - International Edition,2008,vol. 47,p. 7230 - 7233.

31
[ 4916-22-7 ]
[ 65417-22-3 ]

References: [1]Angewandte Chemie - International Edition,2014,vol. 53,p. 13264 - 13268.
Angew. Chem.,2014,vol. 53-126,p. 13480 - 13484.
[2]Angewandte Chemie - International Edition,2008,vol. 47,p. 7230 - 7233.
[3]Chemical Communications,2010,vol. 46,p. 2823 - 2825.
[4]Chemistry - A European Journal,2011,vol. 17,p. 7298 - 7303.

32
[ 513-35-9 ]
[ 65417-22-3 ]
C₁₆H₁₉NO₂ [ No CAS ]

References: [1]Angewandte Chemie - International Edition,2009,vol. 48,p. 7025 - 7029.
Angewandte Chemie,2009,vol. 121,p. 7159 - 7163.

33
[ 105-45-3 ]
[ 615-36-1 ]
[ 65417-22-3 ]

Yield	Reaction Conditions	Operation in experiment
71%	With copper(l) iodide; 1H-tetrazol-1-ylacetic acid; caesium carbonate; In dimethyl sulfoxide; at 80℃; for 36h;Sealed tube;	General procedure: To a 10mL sealed tube was added CuI (0.05mmol), L4 (0.1mmol), ortho-iodo/bromoaniline (0.5mmol), beta-keto ester/beta-diketone (3.0mmol), Cs2CO3 (1.0mmol), and DMSO (1mL). The reaction mixture was reacted at 80C in a preheated oil bath for 12h (for ortho-iodoanilines) or 36h (for ortho-bromoanilines). The reaction mixture was cooled to room temperature and extracted with ethyl acetate (3×20mL). The combined organic phases were washed with water and brine, dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by flash column chromatograph on silica gel (ethyl acetate/petroleum ether as the eluent) to afford the target products 3a-3s.

References: [1]Tetrahedron,2016,vol. 72,p. 653 - 657.
[2]Synlett,2011,p. 623 - 626.
[3]Organic Letters,2013,vol. 15,p. 362 - 365.

34
[ 1310481-65-2 ]
[ 65417-22-3 ]

Yield	Reaction Conditions	Operation in experiment
85%	With carbon monoxide; palladium diacetate; triphenylphosphine; In N,N-dimethyl-formamide; at 120℃; under 4560.31 Torr; for 72h;Autoclave;	General procedure: To an oven-dried ACE glass pressure tube was added 47 (155 mg, 0.67 mmol), Pd(OAc)2 (15.0 mg, 0.07 mmol), PPh3 (61 mg, 0.23 mmol), and DMF (5 mL). The tube was fitted with a pressure head and the solution was then saturated with CO (three cycles to 6 atm of CO). The reaction mixture was heated at 120 C under CO (6 atm, 72 h). The solvents were removed under reduced pressure and the crude product was purified by chromatography (hexanes/EtOAc, 8:2) affording 5 (107 mg, 0.53 mmol, 79%) as a pale yellow solid. Mp 145-150 C; 1H NMR delta 8.27 (s, 1H), 7.24 (d, J=9.0 Hz, 1H), 7.10 (d, J=2.4 Hz, 1H), 6.88 (dd, J=9.0, 2.4 Hz, 1H), 3.86 (s, 3H), 2.97 (q, J=7.2 Hz, 2H), 1.41 (t, J=7.2 Hz, 3H); 13C NMR delta 156.0, 150.5, 129.4, 128.8, 116.7, 113.8, 112.4, 100.8, 84.3, 56.0, 21.2, 13.4; IR (ATR) 3243, 2973, 2212, 1477, 1218 cm-1; HRMS (ESI) calcd for C12H13N2O (M+H+) 201.1028; found, 201.1023.

References: [1]Tetrahedron,2011,vol. 67,p. 3603 - 3611.

35
[ 912358-41-9 ]
[ 65417-22-3 ]
[ 1225382-91-1 ]

References: [1]Chemistry - A European Journal,2011,vol. 17,p. 7298 - 7303.

36
C₁₁H₁₂⁽²⁾HNO₂ [ No CAS ]
[ 65417-22-3 ]
[ 1082470-54-9 ]

References: [1]Chemistry - A European Journal,2011,vol. 17,p. 7298 - 7303.

37
[ 1313753-17-1 ]
[ 65417-22-3 ]
[ 1313753-18-2 ]

References: [1]Chemistry - A European Journal,2011,vol. 17,p. 7298 - 7303.

38
[ 105-45-3 ]
[ 62-53-3 ]
[ 65417-22-3 ]

References: [1]Chemistry - A European Journal,2011,vol. 17,p. 7298 - 7303.
[2]Journal of Organic Chemistry,2019,vol. 84,p. 4017 - 4024.

39
[ 105-45-3 ]
[ 191171-55-8 ]
[ 65417-22-3 ]

References: [1]Synthesis,2012,vol. 44,p. 3811 - 3814.

40
[ 1416879-34-9 ]
[ 65417-22-3 ]

References: [1]Organic Letters,2013,vol. 15,p. 362 - 365.

41
[ 65417-22-3 ]
[ 885525-21-3 ]