6609-57-0|2-Ethoxybenzonitrile| Ambeed

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Quality Control of [ 6609-57-0 ] Purity: 95% SDS Specification

COA

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NMR

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CNMR

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Product Details of [ 6609-57-0 ]

CAS No. :	6609-57-0
Formula :	C₉H₉NO
M.W :	147.17
SMILES Code :	N#CC1=CC=CC=C1OCC
MDL No. :	MFCD00001789
InChI Key :	DXTLCLWOCYLDHL-UHFFFAOYSA-N
Pubchem ID :	576922

Safety of [ 6609-57-0 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302+H312+H332-H315-H319-H335
Precautionary Statements:	P261-P280-P305+P351+P338

Computational Chemistry of [ 6609-57-0 ] Show Less

Physicochemical Properties

Num. heavy atoms	11
Num. arom. heavy atoms	6
Fraction Csp3	0.22
Num. rotatable bonds	2
Num. H-bond acceptors	2.0
Num. H-bond donors	0.0
Molar Refractivity	42.46
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	33.02 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.1
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	2.34
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.96
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.	1.44
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	2.13
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.99

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.5
Solubility	0.467 mg/ml ; 0.00317 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.	-2.67
Solubility	0.313 mg/ml ; 0.00212 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	-2.99
Solubility	0.149 mg/ml ; 0.00101 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.	-5.54 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)	1.37

Application In Synthesis of [ 6609-57-0 ]

* 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 [ 6609-57-0 ]

[ 6609-57-0 ] Synthesis Path-Downstream 1~35

1
[ 6609-57-0 ]
[ 879-57-2 ]

References: [1]Journal of medicinal and pharmaceutical chemistry,1961,vol. 4,p. 351 - 367.

2
[ 613-69-4 ]
[ 6609-57-0 ]

References: [1]Synthesis,1992,p. 641 - 642.
[2]Journal of the Chemical Society. Perkin Transactions 1 (2001),2001,p. 2704 - 2710.

3
[ 6609-57-0 ]
5-(2-ethoxyphenyl)tetrazole [ No CAS ]

References: [1]Russian Journal of Applied Chemistry,2005,vol. 78,p. 773 - 775.

4
[ 403705-98-6 ]
[ 611-20-1 ]
[ 6609-57-0 ]
[ 90-02-8 ]

References: [1]Journal of the Chemical Society. Perkin Transactions 1 (2001),2001,p. 2704 - 2710.

5
[ 6609-57-0 ]
2-chloromethyl-5-(2-ethoxyphenyl)-1,3,4-oxadiazole [ No CAS ]

References: [1]Russian Journal of Applied Chemistry,2005,vol. 78,p. 773 - 775.

6
[ 6609-57-0 ]
[ 889943-46-8 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2002,vol. 12,p. 865 - 868.
[2]Patent: WO2016/20307,2016,A1 .

7
[ 6609-57-0 ]
[ 224789-21-3 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2002,vol. 12,p. 865 - 868.
[2]Patent: WO2014/131855,2014,A1 .
[3]Patent: WO2016/20307,2016,A1 .

8
[ 6609-57-0 ]
[ 927690-90-2 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2002,vol. 12,p. 865 - 868.
[2]Patent: WO2014/131855,2014,A1 .
[3]Patent: WO2016/20307,2016,A1 .
[4]Patent: WO2009/37556,2009,A1 .

9
[ 107369-63-1 ]
[ 6609-57-0 ]

References: [1]Journal of the Chemical Society. Perkin Transactions 1 (2001),2001,p. 2704 - 2710.

10
[ 90-02-8 ]
<i>N</i>-hydroxy-pentadiyldiamine dihydrobromide [ No CAS ]
[ 6609-57-0 ]

References: [1]Journal of the Chemical Society. Perkin Transactions 1 (2001),2001,p. 2704 - 2710.

11
[ 22921-58-0 ]
[ 6609-57-0 ]

References: [1]Journal of the Chemical Society. Perkin Transactions 1 (2001),2001,p. 2704 - 2710.

12
[ 135-02-4 ]
1-<3.5-dibromo-2.4-dihydroxy-phenyl>-ethanone-(1) [ No CAS ]
[ 6609-57-0 ]

References: [1]Journal of the Chemical Society. Perkin Transactions 1 (2001),2001,p. 2704 - 2710.

13
[ 403705-99-7 ]
[ 6609-57-0 ]

References: [1]Journal of the Chemical Society. Perkin Transactions 1 (2001),2001,p. 2704 - 2710.

14
[ 6609-57-0 ]
[ 25844-84-2 ]

References: [1]Recueil des Travaux Chimiques des Pays-Bas,1901,vol. 20,p. 412.
Chemisches Zentralblatt,1908,vol. 79,p. 1826.

15
[ 6609-57-0 ]
[ 22603-53-8 ]

References: [1]Recueil des Travaux Chimiques des Pays-Bas,1901,vol. 20,p. 412.
Chemisches Zentralblatt,1908,vol. 79,p. 1826.

16
[ 6609-57-0 ]
2-hydroxyamino-3,5-dinitro-benzonitrile [ No CAS ]

References: [1]Recueil des Travaux Chimiques des Pays-Bas,1901,vol. 20,p. 412.
Chemisches Zentralblatt,1908,vol. 79,p. 1826.

17
[ 6609-57-0 ]
[ 58890-58-7 ]

References: [1]Recueil des Travaux Chimiques des Pays-Bas,1901,vol. 20,p. 412.
Chemisches Zentralblatt,1908,vol. 79,p. 1826.

18
[ 6609-57-0 ]
3,5-dinitro-2-(<i>N</i>'-phenyl-hydrazino)-benzonitrile [ No CAS ]

References: [1]Recueil des Travaux Chimiques des Pays-Bas,1901,vol. 20,p. 412.
Chemisches Zentralblatt,1908,vol. 79,p. 1826.

19
[ 74-96-4 ]
[ 611-20-1 ]
[ 6609-57-0 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In acetone;	EXAMPLE II 2-Ethoxy-benzonitrile 25 g (210 mmol) of 2-hydroxylbenzonitrile are heated, together with 87 g of potassium carbonate and 34.3 g (314.8 mmol) of ethyl bromide, in 500 ml of acetone under reflux overnight. The solid is filtered off, the solvent is removed in vacuo and the residue is distilled in vacuo. 30.0 g (97%) of a colorless liquid are obtained. 200 MHz 1H-NMR (DMSO-D6): 1.48, t, 3H; 4.15, quart., 2H; 6.99, dt, 2H; 7.51, dt, 2H.
	With potassium carbonate; In acetone;	EXAMPLE 3A 2-Ethoxybenzonitrile 25 g (210 mmol) of 2-hydroxybenzonitrile are refluxed with 87 g of potassium carbonate and 34.3 g (314.8 mmol) of ethyl bromide in 500 ml of acetone overnight. The solid is filtered off, the solvent is removed under reduced pressure and the residue is distilled under reduced pressure. This gives 30.0 g (97%) of a colourless liquid. 200 MHz 1H-NMR (DMSO-d6): 1.48, t, 3H; 4.15, quart., 2H; 6.99, dt, 2H; 7.51, dt, 2H.
	With potassium carbonate; In acetone;	EXAMPLE 11A 2-Ethoxy-benzonitrile 25 g (210 mmol) of 2-hydroxybenzonitrile, 87 g of potassium carbonate and 34.3 g (314.8 mmol) of ethyl bromide in 500 ml of acetone are refluxed overnight. The solid is filtered off, the solvent is removed under reduced pressure and the residue is distilled under reduced pressure. This gives 30.0 g (97%) of a colourless liquid. 200 MHz 1H-NMR (DMSO-d6): 1.48 (t, 3H); 4.15 (quart., 2H); 6.99 (dt, 2H); 7.51 (dt, 2H).

With potassium carbonate; In acetone;

EXAMPLE 12A 2-Ethoxybenzonitrile 25 g (210 mmol) of 2-hydroxybenzonitrile, 87 g of potassium carbonate and 34.3 g (314.8 mmol) of ethyl bromide are refluxed in 500 ml of acetone overnight. The solid is filtered off, the solvent is removed under reduced pressure and the residue is distilled under reduced pressure. This gives 30.0 g (97%) of a colorless liquid. 200 MHz 1H-NMR (DMSO-d6): 1.48 (t, 3H); 4.15 (quart., 2H); 6.99 (dt, 2H); 7.51 (dt, 2H).

References: [1]Patent: EP1174431,2002,A2 .Location in patent: Page 39.
[2]Journal of the American Chemical Society,2010,vol. 132,p. 9688 - 9692.
[3]Patent: US2003/195210,2003,A1 .
[4]Patent: US6362178,2002,B1 .
[5]Patent: US6476029,2002,B1 .
[6]Patent: US2004/97498,2004,A1 .
[7]Bulletin of the Korean Chemical Society,2016,vol. 37,p. 1509 - 1514.

20
[ 6609-57-0 ]
[ 75-24-1 ]
[ 18637-00-8 ]

Yield	Reaction Conditions	Operation in experiment
	With ammonium chloride; In hexane; chloroform; toluene;	EXAMPLE III 2-Ethoxy-benzamidine hydrochloride 21.4 g (400 mmol) of ammonium chloride are suspended in 375 ml of toluene and the suspension is cooled down to 0 C. 200 ml of a 2 M solution of trimethylaluminum in hexane are added dropwise and the mixture is stirred at room temperature until the evolution of gas has come to an end. After 29.44 g (200 mmol) of <strong>[6609-57-0]2-ethoxybenzonitrile</strong> (example II) have been added, the reaction mixture is stirred overnight at 80 C. (bath). Having been cooled down, the reaction mixture is added, while cooling with ice, to a suspension consisting of 100 g of silica gel and 950 ml of chloroform and the mixture is stirred at room temperature for 30 minutes. Filtration with suction is carried out and the subsequent washing takes place with the same quantity of methanol. The mother liquor is evaporated and the resulting residue is stirred up with a mixture of dichloromethane and methanol (9:1), after which the solid is filtered off with suction and the mother liquor is evaporated. 3.4 g (76%) of a colorless solid are obtained. 200 MHz 1H-NMR (DMSO-D6): 1.36, t, 3H; 4.12, quart., 2H; 7.10, t, 1H; 7.21, d, 1H; 7.52, m, 2H; 9.30, s, broad, 4H.
	With ammonium chloride; In hexane; chloroform; toluene;	EXAMPLE 13A 2-Ethoxybenzamidine hydrochloride 21.4 g (400 mmol) of ammonium chloride are suspended in 375 ml of toluene, and the suspension is cooled to 0 C. 200 ml of a 2 M solution of trimethylaluminum in hexane are added dropwise, and the mixture is stirred at room temperature until the evolution of gas has ceased. Following addition of 29.44 g (200 mmol) of <strong>[6609-57-0]2-ethoxybenzonitrile</strong>, the reaction mixture is stirred at 80 C. (bath) overnight. The cooled reaction mixture is, with ice-cooling, added to a suspension of 100 g of silica gel and 950 ml of chloroform, and the mixture is stirred at room temperature for 30 minutes. The mixture is filtered off with suction and the filter cake is washed with the same amount of methanol. The mother liquor is concentrated, the resulting residue is triturated with a mixture of dichloromethane and methanol (9:1), the solid is filtered off with suction and the mother liquor is concentrated. This gives 30.4 g (76%) of a colorless solid. 200 MHz 1H-NMR (DMSO-d6): 1.36 (t, 3H); 4.12 (quart., 2H); 7.10 (t, 1H); 7.21 (d, 1H); 7.52 (m, 2H); 9.30 (s, broad, 4H).

References: [1]Patent: US2003/195210,2003,A1 .
[2]Patent: US2004/97498,2004,A1 .

21
[ 6609-57-0 ]
2-ethoxy-5-[(4-ethyl-1-piperazinyl)sulfonyl]-benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With chlorosulfonic acid; thionyl chloride;	Preparation 7 2-ethoxy-5-(4-ethyl-1-piperazinylsulfonyl)benzonitrile Commercially available <strong>[6609-57-0]2-ethoxybenzonitrile</strong> (25 g, 0.17 Mol) was added dropwise to an ice cooled mixture of chlorosulfonic acid (50.8 mL, 0.765 Mol) and thionyl chloride (12.4 mL, 0.17 Mol) so as to keep the temperature below 10 C. The reaction was then stirred at ambient temperature for 18 h before being poured onto ice/water. This mixture was stirred 1 hr before the precipitated material was filtered off. The resultant solid was dissolved in acetone (300 mL) and triethylamine (25 mL, 0.179 Mol) was added followed by a slow addition of N-ethylpiperazine (25 mL, 0.198 Mol).

References: [1]Patent: US2002/13464,2002,A1 .
[2]Patent: WO2011/16016,2011,A1 .

22
[ 938-73-8 ]
[ 6609-57-0 ]

Yield	Reaction Conditions	Operation in experiment
90%	With thionyl chloride; In 5,5-dimethyl-1,3-cyclohexadiene;	4.2 2-Ethoxybenzamidine hydrochloride 6 2-Ethoxybenzonitrile was prepared from 2-ethoxybenzamide 5 according to the method reported by Nowakowski 23 in 89% yield (lit. 23 yield 92%); Rf (hexane/EtOAc 9:1) 0.45; numax (crystal): 2231 cm-1 (C?N). 1H NMR (CDCl3, delta ppm): 7.57-7.51 (m, 2H, 4-H and 5-H of C6H4), 7.01 (d, J 7.3 Hz, 1H, 6-H of C6H4), 6.97 (d, J 8.8 Hz, 1H, 3-H of C6H4), 4.17 (q, J 7 Hz, 2H, OCH2), 1.49 (t, J 7.1 Hz, 3H, CH3). Ethyl 2-ethoxybenzimidate hydrochloride was synthesized by passing dry HCl(gas) through the solution of 2-ethoxybenzonitrile in anhydrous ethyl alcohol. This compound was obtained as a white solid (46%); mp 49-54 C; Rf (hexane/EtOAc 7:3) 0.36. 1H NMR (CDCl3, delta ppm): 13.01 (br s, 1H, NH), 10.14 (br s, 1H, NH), 8.04 (dd, J 1.7 and 8 Hz, 1H, 6-H of C6H4), 7.74-7.70 (m, 1H, 4-H of C6H4), 7.18-7.14 (m, 2H, 3-H and 5-H of C6H4), 5.04 (q, J 7 Hz, 2H, NCOCH2), 4.39 (q, J 7 Hz, 2H, OCOCH2), 1.63 (t, J 7.1 Hz, 3H, NCOCH2CH3), 1.57 (t, J 6.8 Hz, 3H, OCOCH2CH3).
90%		General procedure: BrCCl3 (900 mg, 4.6 mmol) was added to PPh3 (1.22 g, 4.6 mmol) in dry CH2Cl2 (12 mL) and the resulting mixture was stirred at room temperature for 20 min, during which time the solution turned from yellow to red-brownish in colour.Thereafter, 3-chlorobenzamide (1i, 500 mg, 3.2 mmol) was added. Thereaction mixture was heated under reflux for 25 min. Then, dry Et3N (465 mg, 4.6 mmol) was added dropwise with a syringe over 1 min.The reaction mixture was heated under reflux for 12 h. Thereafter,it was cooled to room temperature and added to cold water (50 mL).The mixture was extracted with dichloromethane (2 × 30 mL) and chloroform (30 mL). The combined organic phases were dried over anhydrous MgSO4, concentrated under reduced pressure and subjected to column chromatography on silica gel (CH2Cl2/hexane 4 : 1) to give 3-chlorobenzonitrile (2i, 320 mg, 72%) as a colourless solid.
	With thionyl chloride; In toluene;	Ib) Preparation of 2-ethoxybenzonitrile 260 kg of thionyl chloride are added at 85-95 C. to a suspension of 250 kg of 2-ethoxybenzamide in toluene under metering control. The reaction mixture is stirred in the presence of heat. Thionyl chloride and toluene are then distilled off in vacuo. The product is employed in the subsequent stage as a crude product. Yield: 228.5 kg (crude product) 1H-NMR: delta=1.45 (t, 3H), 4.15 (q, 2H), 7.0 (m, 2H, phenyl), 7.5 (m, 2H, phenyl) MS: 312 (2M+NH4, 35), 165 (M+NH4, 100), 147 (5)

References: [1]Tetrahedron,2013,vol. 69,p. 474 - 480.
[2]Journal of Chemical Research,2014,vol. 38,p. 80 - 84.
[3]Patent: US2002/137930,2002,A1 .

23
[ 6609-57-0 ]
[ 879-57-2 ]

Yield	Reaction Conditions	Operation in experiment
97%	With hydroxylamine; In ethanol; water; at 50℃; for 12h;	Hydroxylamine (Fluka 55458; 50% in water; 4.08 ml 67.95 mmol; 5 eq.) was added to a solution of <strong>[6609-57-0]2-ethoxybenzonitrile</strong> (Fluorochem 18661 ; 2 g; 13.59 mmol; 1 eq.) in EtOH (30 ml.) and the reaction mixture was stirred at 5O0C for 12 hours. Evaporation in vacuo gave a white solid, which was further dried under high vaccum to afford the title compound (2.38 g: 97%) as a white solid.HPLC (Method A) : Rt 1.22 min (purity 98.2%). LC/MS : 181.0 (M+H)+.
90%	With hydroxylamine hydrochloride; potassium carbonate; In ethanol; for 4h;Reflux;	Add 97% in a 250mL four-necked bottleCompound IV 15.2g (0.1mol),9g (0.13mol) of hydroxylamine hydrochloride,17.9g (0.13mol) was added to 100mL of ethanol,The reaction was refluxed for 4 h.TLC traces the reaction to Compound IV completely, drops to room temperature, and removes the potassium salt in the reaction solution by filtration.The filtrate was evaporated to 80% ethanol, and a white solid precipitated upon cooling.Filter by suction and recover the filtrate.A white solid was obtained in an amount of 16.2 g, yield 90%.
89%	With hydroxylamine hydrochloride; triethylamine; In ethanol; at 50 - 60℃; for 2h;Reflux;	To a 250 mL three-necked flask, 100 mL of ethanol, 13.8 g (0.2 mol) of hydroxylamine hydrochloride and 20 g (0.2 mol) of triethylamine were added, and the mixture was heated to 50-60 C for 1 h, and free hydroxylamine hydrochloride. After 1 h, 18 g of compound 4 (<strong>[6609-57-0]o-ethoxybenzonitrile</strong>) was added to the flask, and the mixture was refluxed for 2 h. The compound 4 disappeared by TLC. Ethanol was distilled off, and 150 mL of water was added to the flask to dissolve the triethylamine hydrochloride. The mixture was filtered under suction, and the cake was compound 3, which was dried to give a white solid.

References: [1]Patent: WO2009/43890,2009,A1 .Location in patent: Page/Page column 54.
[2]Patent: CN108341808,2018,A .Location in patent: Paragraph 0024; 0025; 0026.
[3]Patent: CN108912106,2018,A .Location in patent: Paragraph 0021; 0022; 0023; 0024.
[4]Journal of Medicinal Chemistry,2012,vol. 55,p. 10540 - 10550.
[5]ChemMedChem,2019,vol. 14,p. 1257 - 1270.

24
[ 64-17-5 ]
[ 394-47-8 ]
[ 6609-57-0 ]

References: [1]Synthetic Communications,2010,vol. 40,p. 2122 - 2129.

25
[ 6609-57-0 ]
[ 37806-29-4 ]

References: [1]Journal of the American Chemical Society,2010,vol. 132,p. 9688 - 9692.
[2]Journal of Medicinal Chemistry,2016,vol. 59,p. 3471 - 3488.
[3]ACS Medicinal Chemistry Letters,2011,vol. 2,p. 626 - 631.

26
[ 6609-57-0 ]
5-Chlorosulfonyl-2-ethoxybenzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With chlorosulfonic acid; at 7℃;Cooling with ice;	2-ethoxy benzonitrile (25g, 170 mmol) was added to an ice cold solution of chloro sulfonic acid (183.7g, 1.57mol) over a period of one hour. The temperature of the reaction mixture was maintained at about 5C to 7C. The reaction mixture was stirred at about 5C to 7C overnight. The reaction mass was added into ice water (500 mL) slowly at 100C to 15C. The suspension was stirred for about 1 hour, filtered under nitrogen atmosphere to obtain 5-chlorosulfonyl-2-ethoxy benzonitrile as yellow solid which was used directly in next step.

References: [1]Patent: WO2011/16016,2011,A1 .Location in patent: Page/Page column 13.

27
[ 6609-57-0 ]
[ 224785-90-4 ]

References: [1]Patent: WO2011/16016,2011,A1 .

28
[ 6609-57-0 ]
[ 1169861-31-7 ]

References: [1]Patent: WO2011/16016,2011,A1 .

29
[ 6609-57-0 ]
2-ethoxy-N-hydroxy-5-[(4-ethylpiperazin-1-yl)sulfonyl]benzene carboximidamidine [ No CAS ]

References: [1]Patent: WO2011/16016,2011,A1 .

30
[ 6609-57-0 ]
2-ethoxy-5-(4-ethyl-1-piperazinylsulfonyl)benzamidine tetraacetate [ No CAS ]

References: [1]Patent: WO2011/16016,2011,A1 .

31
[ 6609-57-0 ]
[ 53623-81-7 ]

Yield	Reaction Conditions	Operation in experiment
89%	With hydroxylamine hydrochloride; triethylamine; In ethanol; for 4h;Reflux;	150 mL of ethanol, 4.14 g (0.06 mol) of hydroxylamine hydrochloride and 6 g (0.06 mol) of triethylamine were placed in a 250 mL three-necked flask, and heated to 50-60 C for 1 h.After 1 h, 7.2 g of compound VII was added to the flask, and the reaction was refluxed for 4 h.The compound VII disappeared by TLC, and ethanol was removed by rotary evaporation. 150 mL of water was added to the flask to dissolve the triethylamine hydrochloride, and the residue was filtered and filtered.The cake was Compound VIII, and after drying, it was obtained as a white solid, 9.61 g, yield 89%.
	With trimethylaluminum; ammonium chloride; In toluene; at 0 - 80℃; for 7h;	To a solution of <strong>[6609-57-0]2-ethoxybenzonitrile</strong> (2, 10 g, 68 mmol) in toluene (150 mL) was added AICH3CINH2 (1 eq). The methylchloroaluminum amide was freshly prepared, in-situ; NH4CI (0.535 g, 10 mmol) was dissolved in dry toluene (10 mL) at 000 and trimethylaluminum (2 M in toluene, 5.0 mL, 10 mmol) was added and the reaction was warmed to r.t. and stirred for 1 hour to give theAICH3CINH2, which was used directly. The mixture was stirred at 80 00 for 6 hours. The reaction mixture was concentrated under vacuo to give crude I24a (8.42 g, 75.4% yield). ESI-MS (Mi-i): 165 calc. for 09H12N20: 164.2.
	With amino(methyl)aluminum chloride; In toluene; at 80℃; for 6h;	Preparation of intermediate l-34a: 2-Ethoxybenzamidine To a solution of <strong>[6609-57-0]2-ethoxybenzonitrile</strong> (2, 10 g, 68 mmol) in toluene (150 ml_) was added AICH3CINH2 (1 eq). The methylchloroaluminum amide was freshly prepared, in-situ; NH4CI (0.535 g, 10 mmol) was dissolved in dry toluene (10 ml_) at 0 C and trimethylaluminum (2 M in toluene, 5.0 ml_, 10 mmol) was added and the reaction was warmed to r.t. and stirred for 1 hour to give the AICH3CINH2, which was used directly. The mixture was stirred at 80 C for 6 hours. The reaction mixture was concentrated under vacuo to give crude l-34a (8.42 g, 75.4% yield). ESI-MS (M+1 ): 165 calc. for C9H12N2O: 164.2.

References: [1]Patent: CN108440519,2018,A .Location in patent: Paragraph 0021; 0025; 0026; 0027.
[2]Patent: WO2014/131855,2014,A1 .Location in patent: Page/Page column 138; 139.
[3]Patent: WO2016/20307,2016,A1 .Location in patent: Page/Page column 69.

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[ 1229017-09-7 ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 10540 - 10550.

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[ 1229017-10-0 ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 10540 - 10550.

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[ 913058-73-8 ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 10540 - 10550.

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[ 1153409-15-4 ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 10540 - 10550.

Historical Records

Technical Information

• Alkyl Halide Occurrence • Benzylic Oxidation • Birch Reduction • Blaise Reaction • Blanc Chloromethylation • Catalytic Hydrogenation • Complex Metal Hydride Reductions • Friedel-Crafts Reaction • Hydride Reductions • Hydrogenolysis of Benzyl Ether • Nomenclature of Ethers • Preparation of Aldehydes and Ketones • Preparation of Alkylbenzene • Preparation of Amines • Preparation of Ethers • Reactions of Benzene and Substituted Benzenes • Reactions of Ethers • Ritter Reaction • Thorpe-Ziegler Reaction • Vilsmeier-Haack Reaction

Related Functional Groups of
[ 6609-57-0 ]

Aryls

A204855 [6476-32-0]

2-Phenoxybenzonitrile

Similarity: 0.98

A123455 [189439-24-5]

4-(Benzyloxy)-2-hydroxybenzonitrile

Similarity: 0.96

A380122 [53005-44-0]

2-Methoxy-6-methylbenzonitrile

Similarity: 0.95

A160434 [152775-45-6]

4-Methoxy-3,5-dimethylbenzonitrile

Similarity: 0.91

A587584 [39835-11-5]

2-Hydroxy-4-methoxybenzonitrile

Similarity: 0.91

Ethers

A204855 [6476-32-0]

2-Phenoxybenzonitrile

Similarity: 0.98

A123455 [189439-24-5]

4-(Benzyloxy)-2-hydroxybenzonitrile

Similarity: 0.96

A380122 [53005-44-0]

2-Methoxy-6-methylbenzonitrile

Similarity: 0.95

A160434 [152775-45-6]

4-Methoxy-3,5-dimethylbenzonitrile

Similarity: 0.91

A587584 [39835-11-5]

2-Hydroxy-4-methoxybenzonitrile

Similarity: 0.91

Nitriles

A204855 [6476-32-0]

2-Phenoxybenzonitrile

Similarity: 0.98

A123455 [189439-24-5]

4-(Benzyloxy)-2-hydroxybenzonitrile

Similarity: 0.96

A380122 [53005-44-0]

2-Methoxy-6-methylbenzonitrile

Similarity: 0.95

A160434 [152775-45-6]

4-Methoxy-3,5-dimethylbenzonitrile

Similarity: 0.91

A587584 [39835-11-5]

2-Hydroxy-4-methoxybenzonitrile

Similarity: 0.91

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CAS No.: 6609-57-0

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