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5-Bromo-1-methyl-1H-indole-3-carbaldehyde

5-Bromo-1-methyl-1H-indole-3-carbaldehyde

5-Bromo-1-methyl-1H-indole-3-carbaldehyde

CAS No.: 10102-94-0

Category Products

Cat.NO.:A929545 Purity:95%

Product Details of [ 10102-94-0 ]

CAS No. :	10102-94-0
Formula :	C₁₀H₈BrNO
M.W :	238.08
SMILES Code :	O=CC1=CN(C)C2=C1C=C(Br)C=C2
MDL No. :	MFCD03906373
InChI Key :	NZJJLQUTQOICBN-UHFFFAOYSA-N
Pubchem ID :	778451

Safety of [ 10102-94-0 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 10102-94-0 ] Show Less

Physicochemical Properties

Num. heavy atoms	13
Num. arom. heavy atoms	9
Fraction Csp3	0.1
Num. rotatable bonds	1
Num. H-bond acceptors	1.0
Num. H-bond donors	0.0
Molar Refractivity	56.29
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	22.0 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.12
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	2.15
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.75
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.	1.88
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	2.74
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.33

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.12
Solubility	0.182 mg/ml ; 0.000764 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.	-2.24
Solubility	1.36 mg/ml ; 0.0057 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	-3.65
Solubility	0.0529 mg/ml ; 0.000222 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	Yes
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.	-6.23 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	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)	1.34

Application In Synthesis of [ 10102-94-0 ]

* 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 [ 10102-94-0 ]

[ 10102-94-0 ] Synthesis Path-Downstream 1~35

1
[ 10102-94-0 ]
[ 41003-94-5 ]
[ 90289-62-6 ]
[ 90289-63-7 ]

References: [1]Liebigs Annalen der Chemie,1984,vol. 1984,p. 600 – 607.

Yield	Reaction Conditions	Operation in experiment
90.1%		General procedure: 5-Fluoroindole-3-carbaldehyde (0.5 g, 3.07 mmol) and tetrahydrofuran (10 mL) were sequentially added to a 100 mL one-neck round bottom flask, cooled to 0 C, and slowly added NaH (60%, 196 mg, 4.91 mmol) After reacting for 10 minutes,Transfer to room temperature for 1 h, add MeI (0.38 mL, 6.14 mmol),The reaction was carried out at room temperature for 15.5 h, quenched with water (5 mL), and then evaporated to ethyl ether (ethyl acetate) (ethyl acetate (40mL×1)), washed with water (20mL×3), and then ethyl acetate was collected and then purified by column chromatography ( petroleum ether) /ethyl acetate (v/v) = 5/1) to give the title compound as a white solid(0.50 g, 92%).

4
[ 19012-03-4 ]
[ 10102-94-0 ]
[ 25055-65-6 ]
[ 25055-66-7 ]
N-methyl-2,6-dibromoindole-3-carbaldehyde [ No CAS ]

References: [1]Environmental Toxicology and Chemistry,2001,vol. 20,p. 589 – 596.

5
[ 877-03-2 ]
[ 74-88-4 ]
[ 10102-94-0 ]

Yield	Reaction Conditions	Operation in experiment
96%		5-bromoindole-3-carbaldehyde 2 (10 mmol) was dissolved in acetonitrile and to this powdered NaOH (5 mmol) was added and stirred for 10 min. Methyl iodide (10 mmol) was added dropwise to the reaction mixture. After 3h of stirring at room temperature, the solvent was completely evaporated. It was extracted with ethyl acetate (3×20 ml) and dried over Na2SO4. The combined organic layer was concentrated in vacuo to give a light yellow color solid purified by recrystallization with diethyl ether. Pale yellow solid; Yield: 96%; mp 122-124 C; IR (KBr) numax 3103, 2923, 2813, 1700, 1654. 1533, 1467, 1369, 1083, 799, 726; 1H NMR (DMSO-d6, 300 MHz) delta 9.88 (s, 1H), 8.33 (s, 1H), 8.23 (d, J = 1.70 Hz, 1H), 7.60 (d, J = 8.68 Hz, 1H), 7.48 (dd, J = 2.08, 8.87 Hz, 1H), 3.89 (s, 3H); TOF-HRMS (m/z) for C10H8BrNO, calculated 237.9862, observed 237.9855 [M+1] +
91%	With sodium hydride; In tetrahydrofuran; at 0℃; for 1.83333h;	5-Bromo-1-methyl-lH-indole-3-carbaldehyde; 5-Bromo-1H-indole-3-carbaldehyde (4.8 mmol, 1076 mg) was dissolved in 15 mL of THF and the solution was cooled to 0 C under N2-athmosphere. Sodium hydride (11.7 mmol, 280 mg) was added carefully in portions and iodomethane (8.1 mmol, 1150 mg) was added. The mixture was stirred at 0 C for 1 h. More iodomethane (8.1 mmol, 1150 mg) was added and the stirring continued for 50 min. The mixture was poured over ice and the resulting slurry was extracted with EtOAc. The organic layer was dried over Na2SO4, filtered and evaporated. This gave 1037 mg (91 %) of the title product. ‘H NMR (400 MHz, MeOH-d4) 8 9.82 (s, 1H), 8,29 (m, 1H), 8.06 (s, 1H), 7.43 (m, 2H), 3.89 (s, 3H)
81%		General procedure: To a suspension of NaH 60% in oil (2.25 equiv.) in dry DMF(0.8 mL/mmol) was added, at 0 C and under nitrogen atmosphere, a solution of indolecarboxaldehyde (1 equiv.) in dry DMF (2.5 mL/mmol). After stirring for 30 min at rt, alkyl halide (1.0e3.0 equiv.)was slowly added. After stirring overnight, the reaction wasquenched by addition of water and the product was extracted withdiethyl ether. The organic layer was dried over MgSO4, filtered offand concentrated under vacuum. The crude product was purifiedby column chromatography on silica gel.

		General procedure: Compounds 7-9 were synthesized from the corresponding compounds 4-6. A solution of compounds 4-6 (60 mmol) in THF (30 mL) were added dropwise to a suspension of NaH (3.60 g, 60% dispersion in mineral oil, 150 mmol) in THF (30 mL) at 0 C. After stirring for 15 min, the heterogeneous mixture was treated with iodomethane (5.04 mL, 79.2 mmol) at room temperature for 1 h. Then the reaction mixture was cooled to 0 C, quenched with saturated NH4Cl (60 mL), and extracted with ether (3 * 50 mL). The organic layers were combined, washed with brine, dried over anhydrous Na2SO4 and concentrated in vacuo to give 1-Methyl-1H-indole-3-carboxaldehyde (7-9), a light brown solid. The crude 7-9 were used in the next step without any further purification.
	With sodium hydride; In tetrahydrofuran; at 0 – 20℃; for 24h;	General procedure: The relevant indole-3-carboxaldehyde (2a-c, 10 mmol) in THF(25 mL) was added dropwise to a stirred solution of NaH (25 mmol)in THF (25 mL) at 0 C and CH3I (13.2 mmol) was added after 15 minstirring. The reaction mixturewas moved to room temperature andstirred for further 24 h. Then the solvent was removed in vacuumand the residue was extracted by ethyl acetate. The organic layerwas washed with brine, dried over anhydrous sodium sulfate,filtered and concentrated in vacuum. Recrystallization affordedcompound 3a-c with yields of 93.4-97.5%.

References: [1]Tetrahedron,2005,vol. 61,p. 1793 – 1801.
[2]Journal of Medicinal Chemistry,2009,vol. 52,p. 6217 – 6223.
[3]European Journal of Medicinal Chemistry,2001,vol. 36,p. 545 – 553.
[4]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 3024 – 3028.
[5]Patent: WO2005/66132,2005,A1 .Location in patent: Page/Page column 47.
[6]European Journal of Medicinal Chemistry,2016,vol. 122,p. 408 – 418.
[7]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 1793 – 1798.
[8]European Journal of Medicinal Chemistry,2015,vol. 99,p. 125 – 137.
[9]ChemMedChem,2016,vol. 11,p. 1446 – 1458.
[10]European Journal of Medicinal Chemistry,2018,vol. 156,p. 722 – 737.
[11]Organic Letters,2019,vol. 21,p. 2048 – 2051.

6
[ 10102-94-0 ]
[ 400071-95-6 ]

References: [1]European Journal of Medicinal Chemistry,2001,vol. 36,p. 545 – 553.
[2]Organic Letters,2019,vol. 21,p. 2048 – 2051.

7
[ 10102-94-0 ]
[ 38622-91-2 ]
5-(5′-bromo-1′-methyl-3′-indolyl)oxazole [ No CAS ]

References: [1]Tetrahedron,2005,vol. 61,p. 1793 – 1801.

8
[ 10102-94-0 ]
[ 31499-72-6 ]
1-(5-bromo-1-methyl-1H-indol-3-yl)-5-(2,6,6-trimethylcyclohex-2-enyl)-pent-1-en-3-one [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,2005,vol. 13,p. 1893 – 1899.

9
[ 10102-94-0 ]
[ 7333-52-0 ]
5-bromo-3-cyclopentylidenemethyl-1-methyl-1<i>H</i>-indole [ No CAS ]

References: [1]Tetrahedron Letters,2005,vol. 46,p. 6549 – 6553.

10
[ 931127-52-5 ]
[ 10102-94-0 ]
4-(5-bromo-1-methyl-1<i>H</i>-indol-3-ylmethylene)-5-[1,2,3]thiadiazol-5-yl-2,4-dihydro-pyrazol-3-one [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 1793 – 1798.

11
[ 10075-50-0 ]
[ 10102-94-0 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 1793 – 1798.
[2]European Journal of Medicinal Chemistry,2001,vol. 36,p. 545 – 553.
[3]Chemical Biology and Drug Design,2011,vol. 77,p. 182 – 188.
[4]European Journal of Medicinal Chemistry,2015,vol. 99,p. 125 – 137.
[5]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 3024 – 3028.
[6]ChemMedChem,2016,vol. 11,p. 1446 – 1458.
[7]RSC Advances,2016,vol. 6,p. 30412 – 30424.
[8]European Journal of Medicinal Chemistry,2018,vol. 156,p. 722 – 737.
[9]Organic Letters,2019,vol. 21,p. 7702 – 7707.

12
[ 10102-94-0 ]
C₃₀H₃₂Br₂N₂ [ No CAS ]

References: [1]Tetrahedron Letters,2005,vol. 46,p. 6549 – 6553.

13
[ 10102-94-0 ]
5-bromo-1-methyl-1<i>H</i>-indole-3-carboxylic acid pyridin-4-ylamide [ No CAS ]

References: [1]European Journal of Medicinal Chemistry,2001,vol. 36,p. 545 – 553.

14

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