1075-35-0|5-Chloro-2-methylindole| Ambeed

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Quality Control of [ 1075-35-0 ] Purity: 98% SDS Specification

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Product Details of [ 1075-35-0 ]

CAS No. :	1075-35-0
Formula :	C₉H₈ClN
M.W :	165.62
SMILES Code :	CC(N1)=CC2=C1C=CC(Cl)=C2
MDL No. :	MFCD00005619
InChI Key :	WUVWAXJXPRYUME-UHFFFAOYSA-N
Pubchem ID :	70636

Safety of [ 1075-35-0 ]

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

Computational Chemistry of [ 1075-35-0 ] Show Less

Physicochemical Properties

Num. heavy atoms	11
Num. arom. heavy atoms	9
Fraction Csp3	0.11
Num. rotatable bonds	0
Num. H-bond acceptors	0.0
Num. H-bond donors	1.0
Molar Refractivity	48.27
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	15.79 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	3.08
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	3.13
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.	2.46
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	3.63
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.87

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.41
Solubility	0.064 mg/ml ; 0.000387 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.	-3.08
Solubility	0.138 mg/ml ; 0.000834 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	-4.28
Solubility	0.00873 mg/ml ; 0.0000527 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.	-5.12 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	2.0
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)	1.24

Application In Synthesis of [ 1075-35-0 ]

* 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.

Upstream synthesis route of [ 1075-35-0 ]
Downstream synthetic route of [ 1075-35-0 ]

[ 1075-35-0 ] Synthesis Path-Upstream 1~1

1
[ 1075-35-0 ]
[ 124-38-9 ]
[ 21296-93-5 ]

References: [1] Angewandte Chemie - International Edition, 2014, vol. 53, # 39, p. 10476 - 10480[2] Angew. Chem., 2014, vol. 126, # 39, p. 10644 - 10648,5.

[ 1075-35-0 ] Synthesis Path-Downstream 1~35

1
[ 1075-35-0 ]
[ 33513-42-7 ]
[ 57335-86-1 ]

Yield	Reaction Conditions	Operation in experiment
99%		0.96 g of POCl3 was added drop wise to a solution of 2-methyl-5-chloroindole (1.0 g) in 20 mL of DMF), at 10 C. The mixture was stirred at 50 C. for 1 hr, cooled and diluted with saturated NaHCO3. The suspension was heated at 60 C. for 15 min, cooled, and the precipitates of 2-methyl-5-chloroindole-3-carboxaldehyde were filtered.Yield 1.14 g (99%). An analytical sample was crystallized from EtOH.
92%		General procedure: POCl3 (1.73 mL, 18.6 mmol) was slowly added dropwise into stirred and ice-cooled DMF (5.0 mL). The reaction mixture was stirred at 1-5 C for 20 min, then a solution of corresponding substituted 2-methylindole 6 (15.5 mmol) in DMF (5.0 mL) was slowly added. The resulting reaction mixture was slowly warmed to 35 C and kept at this temperature for 40 min. It was then allowed to cool down to room temperature. To this mixture, ice (~10 g) was added followed by 5 M NaOH solution (31 mL, 155 mmol). The reaction mixture was heated at 95 C for 30 min, and then it was allowed to cool down to room temperature. To this mixture, ice (~10 g) was again added, and the resulting reaction mixture was stirred for 30 min. The desired product was collected by filtration and washed several times with water.

References: [1]Patent: US2010/168417,2010,A1 .Location in patent: Page/Page column 30.
[2]Tetrahedron Letters,2018,vol. 59,p. 1014 - 1018.
[3]Chemistry - A European Journal,2016,vol. 22,p. 12637 - 12640.
[4]European Journal of Medicinal Chemistry,1989,vol. 24,p. 145 - 154.
[5]Green Chemistry,2019,vol. 21,p. 968 - 972.
[6]Organic Letters,2021,vol. 23,p. 6515 - 6519.
[7]Tetrahedron Letters,2021,vol. 82.

2
[ 1075-35-0 ]
[ 79-04-9 ]
[ 620603-92-1 ]

References: [1]Pharmaceuticals,2021,vol. 14.
[2]Journal of Medicinal Chemistry,1990,vol. 33,p. 543 - 552.

3
[ 1075-35-0 ]
[ 14204-27-4 ]
5-chloro-2-methyl-3-(phenylthio)-1H-indole [ No CAS ]

References: [1]Organic Letters,2006,vol. 8,p. 565 - 568.

4
[ 124064-21-7 ]
[ 1075-35-0 ]
[ 479422-23-6 ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 135 - 158.

5
[ 1075-35-0 ]
[ 96-32-2 ]
[ 172595-66-3 ]

Yield	Reaction Conditions	Operation in experiment
63%		To a 250 mL round bottom flask under an atmosphere of nitrogen was added <strong>[1075-35-0]5-chloro-2-methylindole</strong> (5.0 g, 30.2 mmol, 1.0 equiv) and 100 mL THF. The resulting solution was cooled to -78 C. in a dry ice/acetone bath, and n-butyllithium (21 mL of 1.51M solution, 31.72 mmol, 1.05 equiv) was added dropwise over 30 minutes. This was allowed to stir at -78 C. for 30 minutes, at which point zinc chloride (4.12 g, 30.2 mmol, 1.0 equiv) was added as a solution in 5 mL THF dropwise. The resulting mixture was allowed to warm to room temperature. Methyl bromoacetate (2.78 mL, 30.2 mmol, 1.0 equiv) was then added and the reaction allowed to stir fro 24 hours. The reaction mixture was then poured into 500 mL saturated aqueous ammonium chloride and extracted with three 100 mL portions of ethyl acetate. The combined organic layers were washed with water and brine and dried over MgSO4. Filtration and concentration in vacuo gave the crude material which was purified by silica gel chromatography to give the desired product as a yellow oil (4.53 g, 63%). 1H NMR (400 MHz, CHLOROFORM-d) δ 2.35 (s, 3H) 3.64 (s, 2H) 3.68 (s, 3H) 6.99-7.07 (m, 1H) 7.09-7.14 (m, 1H) 7.46 (d, J=2.0 Hz, 1H) 7.95 (br. s., 1H).

References: [1]Patent: US2011/105509,2011,A1 .Location in patent: Page/Page column 41; 42; 43.
[2]Journal of Medicinal Chemistry,2012,vol. 55,p. 5088 - 5109.
[3]Journal of Medicinal Chemistry,2006,vol. 49,p. 135 - 158.
[4]Journal of Medicinal Chemistry,2018,vol. 61,p. 8859 - 8874.

6
[ 1075-35-0 ]
[ 113100-81-5 ]
[ 683813-23-2 ]

Yield	Reaction Conditions	Operation in experiment
94%	With triethylsilane; trifluoroacetic acid; In dichloromethane;	To a solution of <strong>[1075-35-0]5-chloro-2-methylindole</strong> (0.86 g, 5.2 mmol) and 4-(3-Oxo-propyl)-benzoic acid methyl ester (1.0 g, 5.2 mmol) in methylene chloride (50 mL), was added TFA (1.78 g, 15.6 mmol), followed by triethylsilane (1.81 g, 15.6 mmol). The reaction mixture was stirred overnight, quenched with sat. NaHCO3 solution (50 mL), and the organic layer was washed with sat. NaHCO3 solution, water, brine, and dried (Na2SO4). Solvent was removed under reduced pressure, and the residue was purified by flash column chromatography with 10-20% EtOAc/hexanes to yield the desired product in 94% (1.67 g) yield.
94%	With triethylsilane; trifluoroacetic acid; In dichloromethane;	To a solution of <strong>[1075-35-0]5-chloro-2-methylindole</strong> (0.86 g, 5.2 mmol) and 4-(3-oxo-propyl)- benzoic acid methyl ester (1.Og, 5.2 mmol) in methylene chloride (50 mL), was added TFA (1.78 g, 15.6 mmol), followed by triethylsilane (1.81 g, 15.6 mmol). The reaction mixture was stirred overnight, quenched with sat. NaHCO3 solution (50 mL), and the organic layer was washed with sat. NaHCO3 solution, water, brine, and dried (Na2SO4). The solvent was removed under reduced pressure, and the residue was purified by flash column chromatography with 10-20% EtOAc/hexanes to yield the desired product (1.67g) in 94% yield.
94%	With triethylsilane; trifluoroacetic acid; In dichloromethane;	To a solution of <strong>[1075-35-0]5-chloro-2-methylindole</strong> (0.86 g, 5.2 mmol) and 4-(3-oxo-propyl)-benzoic acid methyl ester (1.0 g, 5.2 mmol) in methylene chloride (50 mL), was added TFA (1.78 g, 15.6 mmol), followed by triethylsilane (1.81 g, 15.6 mmol). The reaction mixture was stirred overnight, quenched with sat. NaHCO3 solution (50 mL), and the organic layer was washed with sat. NaHCO3 solution, water, brine, and dried (Na2SO4). Solvent was removed under reduced pressure, and the residue was purified by flash column chromatography with 10-20% EtOAc/hexanes to yield the desired product in 94% (1.67 g) yield.

References: [1]Patent: US2004/82785,2004,A1 .Location in patent: Page 16.
[2]Patent: WO2006/128142,2006,A2 .Location in patent: Page/Page column 34.
[3]Journal of Medicinal Chemistry,2008,vol. 51,p. 3388 - 3413.
[4]Patent: US2008/9485,2008,A1 .Location in patent: Page/Page column 19.
[5]Journal of Medicinal Chemistry,2006,vol. 49,p. 135 - 158.

7
[ 1075-35-0 ]
[ 124064-22-8 ]
[ 872674-58-3 ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 135 - 158.

8
[ 1075-35-0 ]
[ 25015-63-8 ]
5-chloro-2-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-indole [ No CAS ]

References: [1]Journal of the American Chemical Society,2006,vol. 128,p. 15552 - 15553.

9
[ 1075-35-0 ]
[ 936243-76-4 ]

References: [1]Bioorganic and Medicinal Chemistry,2007,vol. 15,p. 3248 - 3265.

10
C₁₄H₁₁ClF₃NO₄ [ No CAS ]
[ 1075-35-0 ]

References: [1]Tetrahedron Letters,2007,vol. 48,p. 7721 - 7725.

11
[ 1075-35-0 ]
[ 93749-47-4 ]
[ 479422-23-6 ]

Yield	Reaction Conditions	Operation in experiment
92%	With triethylsilane; trifluoroacetic acid; In dichloromethane; water; at 20℃; for 48h;	To the above product (1.0 eq) and 5-chloro-2-methyl indole (1.0 eq) in CH2Cl2 (0.12 M) was added triethylsilane (3.0 eq) followed by trifluoroacetic acid (3.0 eq). After being stirred overnight at room temperature, added water and trifluroacetic acid (1.0 eq) to the reaction mixture, stirred at room temperature for two days, diluted with CH2Cl2, washed with 1N NaOH, water, brine, dried over sodium sulfate. Trituration of the material with CH2Cl2 and hexanes afforded the C3 alkylated indole in 92% yield
92%		To the above product (1.0 eq) and 5-chloro-2-methyl indole (1.0 eq) in CH2CI2 (0.12 M) was added triethylsilane (3.0 eq) followed by trifluoroacetic acid (3.0 eq). After being stirred overnight at room temperature, water and trifluroacetic acid (1.0 eq) were added to the reaction mixture, which was stirred at room temperature for two days, diluted with CH2CI2, washed with 1N NaOH, water, and brine, and dried over sodium sulfate. Trituration of the material with CH2CI2 and hexanes afforded the C3 alkylated indole in 92% yield
92%	With triethylsilane; trifluoroacetic acid; In dichloromethane; at 20℃;	To the above product (1.0 eq) and 5-chloro-2-methyl indole (1.0 eq) in CH2Cl2 (0.12 M) was added triethylsilane (3.0 eq) followed by trifluoroacetic acid (3.0 eq). After being stirred overnight at room temperature, added water and trifluroacetic acid (1.0 eq) to the reaction mixture, stirred at room temperature for two days, diluted with CH2Cl2, washed with 1N NaOH, water, brine, dried over sodium sulfate. Trituration of the material with CH2Cl2 and hexanes afforded the C3 alkylated indole in 92% yield

References: [1]Patent: US2004/82785,2004,A1 .Location in patent: Page 10.
[2]Patent: WO2006/128142,2006,A2 .Location in patent: Page/Page column 25.
[3]Patent: US2008/9485,2008,A1 .Location in patent: Page/Page column 12.
[4]Tetrahedron,2008,vol. 64,p. 7871 - 7876.

12
[ 1075-35-0 ]
5-chloro-3-iodo-2-methyl-1H-indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With iodine; p-Chlorothiophenol; In ethanol; for 1.16667h;	A solution of iodine (14 g) was added dropwise over 10 mins to a solution of the 5-chloro- 2-methyl indole (8.3 g) and 4-chlorothiophenol [(8] g) in ethanol (250 ml) and stirred for 1 hour. The mixture was concentrated in vacuo and the residue was treated with diethyl ether to give the sub-title compound as an off white solid (9.9 g) MS: APCI (+ve): 291 [M+H] [+]

References: [1]Patent: WO2003/101981,2003,A1 .Location in patent: Page 45.

13
[ 1075-35-0 ]
[ 24424-99-5 ]
[ 234107-93-8 ]

Yield	Reaction Conditions	Operation in experiment
81%	With 2-(Dimethylamino)pyridine; In tetrahydrofuran; at 0 - 20℃; for 18.5h;	A. 5-Chloro-2-methyl-indole-1-carboxylic acid tert-butyl ester. A solution containing <strong>[1075-35-0]5-chloro-2-methylindole</strong> (4.0 g, 24.1 mmol) and DMAP (295 mg, 2.42 mmol) in anhydrous THF (100 ML) is cooled to 0 C. A solution containing (Boc)2O (5.27 g, 24.1 mmol) in anhydrous THF (100 ML) is then added over a 20 min period.The reaction mixture is stirred for 2 h at 0 C. and then at ambient temperature for 16 hours.The reaction mixture is concentrated and the crude residue is purified by flash silica gel chromatography (2% EtOAc/hexane to 5% EtOAc/hexane) to provide 5.2 g (81%) of title compound as a pale yellow solid. 1H NMR (300 MHz, CDCl3) δ1.67 (s, 9H), 2.57 (s, 3H), 6.24 (t, J=0.9 Hz, 1H), 7.16 (dd, J=8.8, 2.1 Hz, 1H), 7.38 (d, J=2.1 Hz, 1H), 8.01 (d, J=8.8 Hz, 1H) ppm; MS (EI): m/z 265 (M+).

References: [1]Patent: US2004/102450,2004,A1 .Location in patent: Page/Page column 74-75.
[2]Organic Letters,2019,vol. 21,p. 5514 - 5518.

14
[ 1075-35-0 ]
[ 75-36-5 ]
[ 181299-30-9 ]

Yield	Reaction Conditions	Operation in experiment
	With tin(IV) chloride; In dichloromethane; at 20℃; for 6h;	A mixture of <strong>[1075-35-0]5-chloro-2-methylindole</strong> (248 mg, 0.5 mmol) and acetyl chloride (0.045 mL, 0.6 mmol) in methylene chloride is treated with a 1.0 M solution of tin tetrachloride in methylene chloride (0.55 μL, 0.55 mmol), shaken at room temperature for 6 h, quenched with saturated NaHCO3 and extracted with ethyl acetate. The extracts are combined and concentrated in vacuo. The resultant residue and phenylsulfonyl chloride (0.095 mL, 0.75 mmol) are dissolved in THF, treated with NaH (60 mg, 1.5 mmol) at room temperature, shaken for 6 h, quenched with saturated NaHCO3 and extracted with ethyl acetate. The extracts are combined and concentrated in vacuo to give a residue. This residue is suspended in isopropanol, treated sequentially with aminoguanidine bicarbonate (100 mg, 0.5 mmol) and concentrated HCl (50 μL), heated at 80 C. for 4 h, cooled to room temperature and concentrated in vacuo. This resultant residue is purified by HPLC to afford the title product, 10 mg (5% yield), identified by HPLC and mass spectral analyses, (M+H) 404; retention time 4.72 min.

References: [1]Patent: US2004/2527,2004,A1 .Location in patent: Page/Page column 14.

15
[ 1075-35-0 ]
[ 144-55-8 ]
[ 1571-08-0 ]
[ 241498-13-5 ]

Yield	Reaction Conditions	Operation in experiment
1.98 g (63%)	With triethylsilane; trifluoroacetic acid; In dichloromethane; ethyl acetate;	EXAMPLE 88 4-[(1-benzhydryl-5-chloro-2-methyl-1H-indol-3-yl)methyl]benzoic acid Step 1 To an ice-cold (0 C.) solution of trifluoroacetic acid (1.7 ml, 15 mmol) and triethylsilane (4.8 ml, 30 mmol) in CH2Cl2 (20 mL) was added a solution of <strong>[1075-35-0]5-chloro-2-methylindole</strong> (1.66 g, 10 mmol) and methyl 4-formylbenzoate (1.8 g, 11 mmol) in CH2Cl2 (50 mL) over a period of 5 min. The resulting homogeneous solution was stirred at 0 C. for 1 h and rt for 2 h, at which time EtOAc (150 mL) and aqueous sodium bicarbonate (to pH=8) was added. The organic layer was washed with water and brine, dried over MgSO4 and concentrated. Flash chromatography (Hex/EtOAc, 4/1) gave 1.98 g (63%) of desired intermediate as a light-tan solid.

References: [1]Patent: US6500853,2002,B1 .

16
[ 1075-35-0 ]
[ 4752-10-7 ]
[ 881170-96-3 ]

Yield	Reaction Conditions	Operation in experiment
98%	With aluminum (III) chloride; In 1,2-dichloro-ethane;Reflux; Inert atmosphere;	In a 500 mL round-bottomed flask, <strong>[1075-35-0]5-chloro-2-methylindole</strong> (1.00 g, 6.04 mmol) and 1,4-dichlorophthalazine (1.26 g, 6.34 mmol) were taken up in 80 mL dichloroethane. Aluminum chloride (1.13 g, 8.46 mmol) was added, and the mixture refluxed overnight, under a nitrogen-filled balloon. After cooling slightly, the reaction mixture was poured into a mixture of ice and 2 M hydrochloric acid. This was stirred until all the ice had melted, and the layers separated. The aqueous layer was extracted with additional dichloroethane, and the combined organic extracts washed with brine, dried over anhydrous magnesium sulfate, filtered, and evaporated to give material of sufficient purity to be used directly in the next step (1.95 g, 98% yield): 1H NMR (DMSO-d6) δ 11.88 (s, 1H), 8.34-8.38 (m, 1H), 8.14-8.19 (m, 1H), 8.04-8.10 (m, 1H), 7.93 (dt, J=8.1, 1.0 Hz, 1H), 7.46 (d, J=8.6 Hz, 1H), 7.20 (d, J=1.8 Hz, 1H), 7.13 (dd, J=8.6, 2.0 Hz, 1H), 2.40 (s, 3H)
		5-Chloro-2-methylindole (0.74 g, 2.26 mmol) and 1,4-dichloro- phthalazine (0.45 g, 2.26 mmol) were treated with 30 mL of 1,2- dichloroethane and 3.2 mmol of AlCl3 (427 mg). The resulting suspension was heated to 65 C overnight. The reaction was cooled and quenched with 3 niL water. The resultant precipitate was filtered and dried under vacuum to give 0.65 g of the sub-title compound. MS: ESI (negative): 326, 328 (M-H).

References: [1]Patent: US2011/105509,2011,A1 .Location in patent: Page/Page column 16; 17.
[2]Patent: WO2006/34419,2006,A2 .Location in patent: Page/Page column 67-68.
[3]Journal of Medicinal Chemistry,2012,vol. 55,p. 5088 - 5109.

17
[ 17347-61-4 ]
[ 1075-35-0 ]
[ 881171-15-9 ]

Yield	Reaction Conditions	Operation in experiment
		3,3-Dimethyl-dihydro-furan-2,5-dione (7.8 mmol, 1.0 g), 5-chloro-2- methylindole (13.8 mmol, 2.28 g), and AlCl3 (9.0 mmol, 1.2 g) were stirred in 100 mL DCE overnight at 65 C. The reaction was cooled and quenched with 10 mL water. The resultant precipitate was filtered and washed with a small amount of DCE giving 1.06 g of the sub-titled compound.

References: [1]Patent: WO2006/34419,2006,A2 .Location in patent: Page/Page column 96.

18
[ 1075-35-0 ]
[ 40064-34-4 ]
[ 54635-62-0 ]

Yield	Reaction Conditions	Operation in experiment
	With phosphoric acid; In acetic acid;	a. A mixture consisting of 100 gm (0.6 mol) of 5-chloro-2-methyl-indole, 100 gm (0.65 mol) of 4-piperidone monohydrate hydrochloride, 900 ml of glacial acetic acid and 450 ml of 4 N phosphoric acid was heated for 2 hours at 80C. Thereafter, the reaction mixture was cooled and then poured into a mixture of ice and ammonia, and the resulting mixture was extracted with ethyl acetate. The organic extract solution was washed with water, dried and evaporated, and the residue was recrystallized from methanol, yielding 108 gm (73% of theory) of 4-(5'-chloro-2'-methyl-3'-indolyl)-1,2,5,6-tetrahydropyridine, m.p. 208-210C.
	With phosphoric acid; In acetic acid; at 80℃;	General procedure: 2-Methyl-1H-indole derivatives (0.5-6 mmol, 1 equiv) were stirred at 80 C in acetic acid (2 mL/1 mmol), 4-piperidone hydrochloride hydrate (1.5-18 mmol, 3 equiv) and 1 M phosphoric acid (1 mL/1 mmol) were added. After 1-2 h, the mixture was poured into ice/ammonia, and extracted with ethyl acetate (3 x 25 mL). The combined organic layers were washed with water and brine, dried, and evaporated in vacuo to give the title compounds. The crude products were purified by silica gel column chromatography (ethylacetate-methanol, gradient) and most of them were converted to the corresponding salts by dissolving the free base in methanol or ethanol and adding one equivalent of oxalic acid or ethanolic HCl solution. The solvent was removed and azeotroped with absolute ethanol in vacuo followed by recrystallization from appropriate solvents.

References: [1]Patent: US3980658,1976,A .
[2]European Journal of Medicinal Chemistry,2013,vol. 63,p. 578 - 588.

19
[ 81327-26-6 ]
[ 1075-35-0 ]

Yield	Reaction Conditions	Operation in experiment
94%	With carbon monoxide;cyclopentadienyl iron(II) dicarbonyl dimer; In toluene; at 120℃; for 5h;	EXAMPLE 10 Synthesis of 5-chloro-2-methylindole In a stainless steel autoclave having an internal volume of 100 mL, 1.09 g (5.1 mmol) of 5-chloro-2-nitrophenylacetone, 72 mg (4 mol %) of cyclopentadienyidicarbonyliron (dimer) and 40 g of toluene were placed under nitrogen atmosphere. After the atmosphere inside of the reactor was substituted by nitrogen gas (10 kgf/cm2) three times, carbon monoxide gas was injected (30 kgf/cm2), and the resulting mixture was reacted at a temperature of 120 C. for 5 hours. After cooling, the reaction solution was subjected to quantitative analysis with liquid chromatography. As a result of it, it was confirmed that 5-chloro-2-nitrophenylacetone was completely disappeared. Thereafter, post-treatment was conducted, and the main product was isolated with silica gel chromatography to obtain 0.79 g (yield 94.0%) of 6-fluoro-2-methylindole.

References: [1]Patent: US2007/83053,2007,A1 .Location in patent: Page/Page column 7.

20
[ 1075-35-0 ]
[ 96-32-2 ]
[ 934990-17-7 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N,N-dimethyl-formamide; at 45℃;	Preparation 1a (δ-chloro^-methylindol-i-yljacetic acid methyl esterA mixture of 5-chloro-2-methyl-1 H-indole (1.0 g), bromoacetic acid methyl ester (0.83 mL), potassium carbonate (2.5 g) and λ/,/V-dimethylformamide (7.0 ml_) was stirred at 450C overnight. The reaction mixture was diluted with 1.0 M aqueous hydrochloric acid and the resulting precipitate collected by filtration and dried to afford (5-chloro-2-methyl-indol-1-yl)acetic acid methyl ester, 1.3 g.1H NMR (DMSO-d6): δ 2.30 (d, J = 0.9 Hz, 3H), 3.70 (s, 3H), 5.10 (s, 2H), 6.25 (t, J = 0.9 Hz, 1H), 7.05 (dd, J = 1.9, 8.7 Hz, 1H), 7.40 (d, J = 8.7 Hz, 1H), 7.45 (d, J = 1.9 Hz, 1H).

References: [1]Patent: WO2007/45867,2007,A1 .Location in patent: Page/Page column 15.
[2]Journal of Medicinal Chemistry,2012,vol. 55,p. 5088 - 5109.

21
[ 557-93-7 ]
[ 873-38-1 ]
[ 1075-35-0 ]

References: [1]Chemistry - A European Journal,2008,vol. 14,p. 1351 - 1356.

22
[ 1075-35-0 ]
(±)-5-chloro-2-methylindoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With sodium cyanoborohydride; In acetic acid; at 20℃; for 16h;	(a) (RS)-5-Chloro-2-methyl-2,3-dihydro-1H-indole To a solution of <strong>[1075-35-0]5-chloro-2-methylindole</strong> (1.00 g, 6.04 mmol) in acetic acid (7 ml) was added portionwise sodium cyanoborohydride (0.76 g, 12.1 mmol) and the reaction mixture was stirred at room temperature for 16 hours. The resulting solution was diluted with ethyl acetate and washed sequentially with water and with 5 N aq. sodium hydroxide solution. The organic phase was dried over sodium sulphate and concentrated in vacuo. The residue was purified by chromatography on silica gel (eluant: heptane/ethyl acetate gradient) to yield the title compound as a colourless oil (1.00 g, 100%); MS (ISP): 170.2 ([{37Cl}M+H]+), 168.3 ([{35Cl}M+H]+).
100%	With sodium cyanoborohydride; acetic acid; at 20℃; for 16h;	To a solution of <strong>[1075-35-0]5-chloro-2-methylindole</strong> (1.00 g, 6.04 mmol) in acetic acid(7 ml) was added portionwise sodium cyanoborohydride (0.76 g, 12.1 mmol) and the reaction mixture was stirred at room temperature for 16 hours. The resulting solution was diluted with ethyl acetate and washed sequentially with water and with 5 N aq. sodium hydroxide solution. The organic phase was dried over sodium sulphate and concentrated in vacuo. The residue was purified by chromatography on silica gel (eluant: <n="22"/>heptane/ ethyl acetate gradient) to yield the title compound as a colourless oil (1.00 g, 100%); MS (ISP): 170.2 ( [{37Cl}M+H]+); 168.3 ([{35C1}M+H]+).
	With 1,1,1,3',3',3'-hexafluoro-propanol; (RuBF4((S,S)-N-Me-Msdpen)(p-cymene)); hydrogen; at 30℃; under 37503.8 Torr; for 20h;Autoclave;	10305] A 50 mE autoclave was charged with 6.3 mg (0.01 mmol, S/C100) of RuBF4((S,S)-N-Me-Msdpen) (p-cymene) obtained in Synthesis Example 18 serving as a catalyst, 0.16 12 g (1 mmol) of <strong>[1075-35-0]5-chloro-2-methylindole</strong>, and 1.2 mE of HFIP, and the reaction was allowed to proceed at30 C. for 20 hours under a hydrogen pressure of 5 MPa. The conversion and the optical purity determined by GC analysis were 99.1% cony. (conversion) and 94.3% cc (optical purity).

References: [1]Patent: US2008/113980,2008,A1 .Location in patent: Page/Page column 8.
[2]Patent: WO2008/58867,2008,A2 .Location in patent: Page/Page column 20-21.
[3]Chemistry - A European Journal,2015,vol. 21,p. 5370 - 5379.
[4]Angewandte Chemie - International Edition,2017,vol. 56,p. 5760 - 5764.
Angew. Chem.,2017,vol. 129,p. 5854 - 5858,5.
[5]Patent: US2016/347678,2016,A1 .Location in patent: Paragraph 0304; 0305.

23
[ 1075-35-0 ]
[ 86-98-6 ]
[ 96-32-2 ]
[ 629644-21-9 ]

Yield	Reaction Conditions	Operation in experiment
		5-Chloro-2-methylindole (0.16 g) and 4,8-dichloroquinoline (0.2 g) were suspended in NMP (0.5 ml) and heated in a microwave at [100W,] 140 C for 60 minutes. When reaction was complete THF (5 ml) was added followed by sodium hydride 60% dispersion in oil (0.12 g). After 30 mins a solution of methyl bromoacetate (0.2 ml) in THF [(1] ml) was added and the mixture stirred at room temperature for 24 hours. Ethyl acetate and saturated brine solution were added, the aqueous phase was separated and extracted with ethyl acetate. The combined organic solution was evaporated to leave a residue which was purified by silica gel chromatography using dichloromethane/ethyl acetate (9: 1) to provide the sub-title product as an oil. (120 mg). MS: APCI (+ve): 399/401/403 [[M+H] +]

References: [1]Patent: WO2003/101981,2003,A1 .Location in patent: Page 31.

24
[ 1075-35-0 ]
[ 13994-61-1 ]
[ 1125617-65-3 ]

References: [1]Organic Letters,2009,vol. 11,p. 1213 - 1216.

25
C₁₃H₉ClF₃NO₃ [ No CAS ]
[ 1075-35-0 ]

References: [1]Tetrahedron,2009,vol. 65,p. 8916 - 8929.

26
[ 445262-62-4 ]
[ 1075-35-0 ]
[ 1194486-30-0 ]

References: [1]Chemistry - A European Journal,2009,vol. 15,p. 8709 - 8712.

27
[ 1075-35-0 ]
[ 102-96-5 ]
[ 1227380-57-5 ]

References: [1]RSC Advances,2018,vol. 8,p. 26407 - 26415.
[2]Tetrahedron,2010,vol. 66,p. 2981 - 2986.

28
[ 1075-35-0 ]
[ 5445-17-0 ]
2-(5-chloro-2-methyl-1H-indol-1-yl)propanoic acid [ No CAS ]