102151-33-7|3-Chloro-4-methoxybenzonitrile| Ambeed

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Quality Control of [ 102151-33-7 ] Purity: 96% SDS Specification

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Product Details of [ 102151-33-7 ]

CAS No. :	102151-33-7
Formula :	C₈H₆ClNO
M.W :	167.59
SMILES Code :	COC1=C(Cl)C=C(C=C1)C#N
MDL No. :	MFCD03093073
InChI Key :	SUFOLDHSHRVSQV-UHFFFAOYSA-N
Pubchem ID :	4323105

Safety of [ 102151-33-7 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H317-H319-H335
Precautionary Statements:	P261-P280-P305+P351+P338

Computational Chemistry of [ 102151-33-7 ] Show Less

Physicochemical Properties

Num. heavy atoms	11
Num. arom. heavy atoms	6
Fraction Csp3	0.12
Num. rotatable bonds	1
Num. H-bond acceptors	2.0
Num. H-bond donors	0.0
Molar Refractivity	42.66
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.	1.99
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	2.25
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.22
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.	1.71
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	2.43
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.12

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.63
Solubility	0.389 mg/ml ; 0.00232 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.	-2.58
Solubility	0.441 mg/ml ; 0.00263 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	-3.22
Solubility	0.101 mg/ml ; 0.000603 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.	-5.72 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)	1.5

Application In Synthesis of [ 102151-33-7 ]

* 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 [ 102151-33-7 ]

[ 102151-33-7 ] Synthesis Path-Downstream 1~35

1
[ 67-56-1 ]
[ 102151-33-7 ]
[ 102151-34-8 ]

References: [1]Journal of Medicinal Chemistry,1986,vol. 29,p. 1065 - 1080.

2
[ 89978-93-8 ]
[ 102151-33-7 ]

References: [1]Journal of Pharmaceutical Sciences,1986,vol. 75,p. 410 - 412.

3
[ 925-90-6 ]
[ 102151-33-7 ]
[ 4394-54-1 ]

References: [1]Journal of Pharmaceutical Sciences,1986,vol. 75,p. 410 - 412.

4
[ 2315-81-3 ]
[ 74-88-4 ]
[ 102151-33-7 ]

Yield	Reaction Conditions	Operation in experiment
	In water; N,N-dimethyl-formamide;	Step A 3-Chloro-4-methoxybenzonitrile (26) Under N2, a solution of 3-chloro-4-hydroxybenzonitrile (15.4 g, 0.1 mole) in dry DMF (75 ml) was added rapidly dropwise to a stirred suspension of sodium hydride (4.0 g, 0.1 mole, 60% oil dispersion) in dry DMF (25 ml). After heating at 70 C. for 2 hours, the mixture was cooled to 20 C. and a solution of methyliodide (30 ml) in dry DMF (50 ml) was added dropwise. Following an 18 hour period at room temperature, the precipitate of sodium iodide was removed by filtration and the solvent was stripped from the filtrate under reduced pressure. The crystalline residue was slurried in water and the product was collected to yield 16.8 g (quant.) of 26, m.p. 105-108 C.
	In water; N,N-dimethyl-formamide;	Step A: 3-Chloro-4-methoxybenzonitrile (26) Under N2, a solution of 3-chloro-4-hydroxybenzonitrile (15.4 g, 0.1 mole) in dry DMF (75 ml) was added rapidly dropwise to a stirred suspension of sodium hydride (4.0 g, 0.1 mole, 60% oil dispersion) in dry DMF (25 ml). After heating at 70 C. for 2 hours, the mixture was cooled to 20 C. and a solution of methyliodide (30 ml) in dry DMF (50 ml) was added dropwise. Following an 18 hour period at room temperature, the precipitate of sodium iodide was removed by filtration and the solvent was stripped from the filtrate under reduced pressure. The crystalline residue was slurried in water and the product was collected to yield 16.8 g (quant.) of 26, m.p. 105-108 C.
	With potassium carbonate; In acetone; at 20℃;	Synthesis of Intermediate (1)[00334] In a 3-neck 100 mL round-bottomed flask, 3 -Chloro-5 -hydroxy benzonitrile (3.5 g, 1 eq.) was mixed with potassium carbonate (4.71 g, 1.5 eq.) using acetone (70 mL, 20 Vol.) as solvent. To this reaction mixture methyl Iodide (6.46 g, 2.0 eq.) was added drop-wise at room temperature and reaction was further stirred at RT for 3-4 h. Reaction completion was monitored on TLC using ethyl acetate: n-hexane (2:8) mobile phase. The reaction mixture was quenched into ice-water slurry (150 mL) and compound was extracted in the ethyl acetate (50 mol x 3). Organic layer was washed with brine solution (50 mol x 3) followed by drying using anhydrous sodium sulphate. Organic layer was concentrated under reduced pressure to afford 3.5 g of crude compound, Yield (92.1 %).

References: [1]Journal of Medicinal Chemistry,1986,vol. 29,p. 1065 - 1080.
[2]Patent: US4642311,1987,A .
[3]Patent: US4853383,1989,A .
[4]Patent: WO2011/109799,2011,A1 .Location in patent: Page/Page column 124.

5
[ 67-56-1 ]
[ 117482-84-5 ]
[ 102151-33-7 ]

References: [1]Journal of Medicinal Chemistry,1997,vol. 40,p. 1634 - 1647.

6
[ 5470-49-5 ]
[ 102151-33-7 ]
[ 189297-37-8 ]

References: [1]Journal of Medicinal Chemistry,1997,vol. 40,p. 1634 - 1647.

7
[ 4920-79-0 ]
[ 143-33-9 ]
C₇H₅ClONCNO₂⁽²⁾H^(1-) [ No CAS ]
[ 10496-75-0 ]
[ 102151-33-7 ]

References: [1]Organic Letters,2007,vol. 9,p. 2803 - 2806.
[2]Organic Letters,2007,vol. 9,p. 2803 - 2806.

8
[ 102151-33-7 ]
[ 177661-25-5 ]

References: [1]Journal of Medicinal Chemistry,1997,vol. 40,p. 1634 - 1647.

9
[ 102151-33-7 ]
4-[2-(3-chloro-4-methoxyphenyl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide [ No CAS ]

References: [1]Journal of Medicinal Chemistry,1997,vol. 40,p. 1634 - 1647.

10
[ 102151-33-7 ]
[ 177661-55-1 ]

References: [1]Journal of Medicinal Chemistry,1997,vol. 40,p. 1634 - 1647.

11
[ 37908-96-6 ]
[ 102151-33-7 ]

References: [1]Journal of Pharmaceutical Sciences,1986,vol. 75,p. 410 - 412.

12
[ 37908-98-8 ]
[ 102151-33-7 ]

References: [1]Journal of Pharmaceutical Sciences,1986,vol. 75,p. 410 - 412.

13
[ 36590-49-5 ]
[ 102151-33-7 ]

References: [1]Journal of Pharmaceutical Sciences,1986,vol. 75,p. 410 - 412.

14
[ 102151-33-7 ]
[ 102976-53-4 ]

References: [1]Journal of Pharmaceutical Sciences,1986,vol. 75,p. 410 - 412.

15
[ 102151-33-7 ]
(+/-)-2-tert-butylamino-3'-chloro-4'-methoxypropiophenone [ No CAS ]

References: [1]Journal of Pharmaceutical Sciences,1986,vol. 75,p. 410 - 412.

16
[ 102151-33-7 ]
[ 102151-35-9 ]

References: [1]Journal of Medicinal Chemistry,1986,vol. 29,p. 1065 - 1080.

17
[ 5470-49-5 ]
[ 75-24-1 ]
[ 102151-33-7 ]
[ 189297-37-8 ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; dichloromethane; chloroform; toluene;	Step 1 Preparation of 3-chloro-4-methoxy-N-[4-(methylsulfonyl)phenyl]benzenecarboximidamide To a suspension of 4-(methylsulfonyl)aniline (10 mmol) in toluene (100 mL), trimethylaluminum (2M solution in toluene, 15 mmol) is added over 15 minutes. The reaction mixture is warmed to room temperature and stirred for 2.5 hours. A solution of <strong>[102151-33-7]3-chloro-4-methoxybenzonitrile</strong> (20 mmol) in toluene (50 mL) is added over 10 minutes and the reaction mixture is heated to 80-85 C. After 20 hours, the reaction mixture is cooled to room temperature and poured over a slurry of silica gel in chloroform. After filtration, the residue is washed with a mixture of methylene chloride/methanol (2/1). The combined filtrates are concentrated in vacuo and the resulting yellowish solid is stirred with a mixture of hexane/ether (2/1, 1000 mL).

References: [1]Patent: US5616601,1997,A .

18
iron(III) chloride [ No CAS ]
N-methyl-N-(p-toluenesulfonyl)-2-chloro-6-fluorobenzohydrazonoyl chloride [ No CAS ]
[ 102151-33-7 ]
[ 168010-83-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; ammonia; In 1,2-dichloro-benzene;	Reference Example 6 Preparation of 3-(2-chloro-6-fluorophenyl)-5-(3-chloro-4-hydroxyphenyl) 1-methyl-1H-1,2,4-triazole To o-dichlorobenzene (200 ml) are added <strong>[102151-33-7]3-chloro-4-methoxybenzonitrile</strong> (40.3 g) and anhydrous iron (III) chloride (42.2 g), which are heated at 120 C. with stirring. To this mixture is added dropwise a solution of N-methyl-N-(p-toluenesulfonyl)-2-chloro-6-fluorobenzohydrazonoyl chloride (62.2 g) in o-dichlorobenzene (300 ml) at 120 C. for 30 minutes with stirring, which are further stirred at 120 C. for 3 hours. After cooling to room temperature, the reaction mixture is poured into a large amount of water and extracted with chloroform. The organic layer is added with aqueous solution of 10% NaOH (200 ml) and aqueous solution of 25% ammonia (200 ml) and stirred at 50 C. for 1 hour. After cooling to room temperature, the organic layer is washed with water, dried over anhydrous magnesium sulfate, concentrated under reduced pressure to give 70.5 g of a crude product of 3-(2-chloro-6-fluorophenyl)-5-(3-chloro-4-methoxyphenyl) 1-methyl-1H-1,2,4-triazole.

References: [1]Patent: US5616594,1997,A .

19
[ 102151-33-7 ]
[ 102151-34-8 ]
3-chloro-4-methoxybenzimidamide hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With ammonia; In methanol; CH3 OH (6 ml)-dioxane; diethyl ether;	Step B 3-Chloro-4-methoxybenzamidine hydrochloride (27) Under N2, a stirred suspension of 26 (16.1 g, 0.096 mole) in CH3 OH (6 ml)--dioxane (20 ml) was cooled in an ice bath and saturated with gaseous HCl. The resulting mixture was refrigerated. After 3 days, the solid mass was suspended in Et2 O and the methyl 3-chloro-4-methoxybenzimidate hydrochloride was collected to afford 17.5 g (77%), m.p. 190-192 C. Methyl 3-chloro-4-methoxybenzimidate hydrochloride, (19.9 g, 0.084 mole) was added to a solution of ammonia (12 g) in CH3 OH (100 ml) cooled to -78 C. The stirred mixture was allowed to warm to room temperature. After 20 hours, the solution was evaporated to dryness under reduced pressure. The solid residue was triturated with Et2 O and collected to yield 17.8 g (96%) of 27, m.p. dec. 243-245 C. A sample triturated with acetone melted at 241-243 C. dec. Analysis calculated for C8 H10 Cl2 N2 O: C, 43.46; H, 4.56, N, 12.67. Found: C, 42.84; H, 4.83; N, 12.74.
	With ammonia; In methanol; CH3 OH (6 ml)-dioxane; diethyl ether;	Step B: 3-Chloro-4-methoxybenzamidine hydrochloride (27) Under N2, a stirred suspension of 26 (16.1 g, 0.096 mole) in CH3 OH (6 ml)--dioxane (20 ml) was cooled in an ice bath and saturated with gaseous HCl. The resulting mixture was refrigerated. After 3 days, the solid mass was suspended in Et2 O and the methyl 3-chloro-4-methoxybenzimidate hydrochloride was collected to afford 17.5 g (77%), m.p. 190-192 C. Methyl 3-chloro-4-methoxybenzimidate hydrochloride, (19.9 g, 0.084 mole) was added to a solution of ammonia (12 g) in CH3 OH (100 ml) cooled to -78 C. The stirred mixture was allowed to warm to room temperature. After 20 hours, the solution was evaporated to dryness under reduced pressure. The solid residue was triturated with Et2 O and collected to yield 17.8 g (96%) of 27, m.p. dec. 243-245 C. A sample triturated with acetone melted at 241-243 C. dec.

References: [1]Patent: US4642311,1987,A .
[2]Patent: US4853383,1989,A .

20
[ 4920-79-0 ]
[ 143-33-9 ]
[ 1007122-94-2 ]
[ 10496-75-0 ]
[ 102151-33-7 ]

References: [1]Journal of Organic Chemistry,2008,vol. 73,p. 1925 - 1934.

22
[ 102151-33-7 ]
[ 1333151-61-3 ]

References: [1]Patent: WO2011/109799,2011,A1 .

23
[ 64-18-6 ]
[ 102151-33-7 ]
[ 1333152-96-7 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrazine hydrate; In N,N-dimethyl-formamide; at 90℃; for 12h;	Synthesis of Intermediate (2)[00336] In a 3-neck 50 mL round-bottomed flask, Intermediate- 1 (3.5 g, 1 eq.) was dissolved in DMF (70 mL, 20 Vol.). Formic acid (18 mL, 5.1 Vol.) and Hydrazine hydrate (18 mL, 5.1 Vol.) was added to this reaction mixture. Reaction mixture was refluxed to 90 C for 12 h. Reaction completion was monitored on TLC using ethyl acetate: n-hexane (5:5) as mobile phase. Reaction mixture was brought to room temperature after completion and quenched into the ice- water slurry (350 mL) and compound was extracted in the Ethyl acetate (100 mL x 3). Organic layer was washed with brine solution (100 mL x 3) followed by drying using anhydrous sodium sulphate. Organic layer was concentrated under reduced pressure to afford 4.0 g of crude compound. Compound was purified by column chromatography using silica 60/120 and ethylacetate: hexane as mobile phase. Column purification was started with 5 % EtOAc in hexane up to 30 % EtOAc. Compound started eluting in 25 % ethylacetate and continued till 30 % EtOAc. Fractions containing compound was distilled out using rotary evaporation at 45 C / 250 mm Hg to obtain 0.7 g of pure compound, Yield (16.2%).

References: [1]Patent: WO2011/109799,2011,A1 .Location in patent: Page/Page column 124-125.

24
[ 90359-73-2 ]
[ 102151-33-7 ]
[ 1409950-48-6 ]

References: [1]Patent: US2013/115190,2013,A1 .
[2]Patent: US9527885,2016,B2 .

25
[ 90359-73-2 ]
[ 102151-33-7 ]
[ 1409950-49-7 ]

Yield	Reaction Conditions	Operation in experiment
84%	With tert.-butyl lithium; In tetrahydrofuran; pentane;	Step 1 To a solution of N,N-diethyl-4-methoxy-2-methylbenzamide (1 g, 4.52 mmol) in THF (9 ml) at -78 C. was added dropwise tert-butyllithium 1.7 M in pentane (3.19 ml, 5.42 mmol) and the solution was stirred for 0.5 h before addition of <strong>[102151-33-7]3-chloro-4-methoxybenzonitrile</strong> (0.757 g, 4.52 mmol) in THF (9 ml). The resulting solution was warmed to rt and stirred for 16 h. The reaction mixture was quenched with water, neutralized with 1 N HCl. The precipitated solid was collected and washed with water to give 3-(3-chloro-4-methoxyphenyl)-6-methoxyisoquinolin-1-ol (1.2 g, 84% yield) as a solid after drying. MS: MS m/z 316.1 (M++1).
84%		To a solution of N,N-diethyl-4-methoxy-2-methylbenzamide (1 g, 4.52 mmol) in THF (9 ml) at -78 C. was added dropwise tert-butyllithium 1.7 M in pentane (3.19 ml, 5.42 mmol) and the solution was stirred for 0.5 h before addition of <strong>[102151-33-7]3-chloro-4-methoxybenzonitrile</strong> (0.757 g, 4.52 mmol) in THF (9 ml). The resulting solution was warmed to rt and stirred for 16 h. The reaction mixture was quenched with water, neutralized with 1 N HCl. The precipitated solid was collected and washed with water to give 3-(3-chloro-4-methoxyphenyl)-6-methoxyisoquinolin-1-ol (1.2 g, 84% yield) as a solid after drying. MS: MS m/z 316.1 (M++1)

References: [1]Patent: US2013/115190,2013,A1 .Location in patent: Page/Page column.
[2]Patent: US9527885,2016,B2 .Location in patent: Page/Page column 46.

26
[ 137042-63-8 ]
[ 102151-33-7 ]

References: [1]Chemical Communications,2013,vol. 49,p. 3146 - 3148.

27
2-chloro-4-ethynyl-1-methoxybenzene [ No CAS ]
[ 102151-33-7 ]

References: [1]Angewandte Chemie - International Edition,2013,vol. 52,p. 6677 - 6680.
Angew. Chem.,2013,vol. 125,p. 6809 - 6612,4.

28
[ 102151-33-7 ]
[ 2315-81-3 ]

Yield	Reaction Conditions	Operation in experiment
3.17 g	With boron tribromide; In dichloromethane; at -78 - 20℃;	To a solution of <strong>[102151-33-7]3-chloro-4-methoxybenzonitrile</strong> (4.25g) in DCM (85m1) was added a -78C dropwise 1M BBr3 in DCM (50.7m1). The reaction mixture was stirred at -78C for 10mm and at rt overnight. The mixture was then stirred at 40C for 4.5d and additional BBr3 sol. (26m1) was added on the first, second and third day, respectively. The reaction mixture wascarefully quenched with water, the solid precipitate was filtrated off. The layers were separated, the aq. phase was washed with DCM and the combined org. layers were dried over MgSO4, filtrated off and evaporated in vacuo. The crude was purified by CC (Buechi Sepacore, 50g cartridge, solvent A: Heptane, solvent B: EA, gradient in %B: 0 to 40, flow rate: 30 mI/mm) to afford 3.17g of a brown oil. LC-MS (A): tR = 0.68 mm; [M+H]: not visible.
3.17 g	With boron tribromide; In dichloromethane; at -78 - 20℃;Inert atmosphere;	To a solution of <strong>[102151-33-7]3-chloro-4-methoxybenzonitrile</strong> (4.25g) in DCM (85 mL) was added a -78C dropwise 1 M sol. of BBr3 in DCM (50.7 mL). The reaction mixture was stirred at -78C for 10 min and at RT overnight. The mixture was then stirred at 40C for 4.5d and additional BBr3 sol. (26 mL) was added on the first, second and third day respectively. The reaction mixture was carefully quenched with water, the solid precipitate was filtrated off. The layers were separated, the aq. phase was washed with DCM and the combined org. layers were dried over MgS04, filtrated off and evaporated in vacuo. The crude was purified by CC (Buchi Sepacore, 50g cartridge, solvent A: Heptane , solvent B: EA, gradient in %B: 0 to 40, flow rate: 30 mL/min) to afford 3.17g of a brown oil. LC-MS (A): tR = 0.68 min; [M+H]+: not visible.

References: [1]Patent: WO2015/75025,2015,A1 .Location in patent: Page/Page column 93.
[2]Patent: WO2015/75023,2015,A1 .Location in patent: Page/Page column 139.

29
[ 102151-33-7 ]
methyl 2-(2-chloro-4-cyanophenoxy)acetate [ No CAS ]

References: [1]Patent: WO2015/75025,2015,A1 .

30
[ 102151-33-7 ]
2-(2-chloro-4-cyanophenoxy)acetic acid [ No CAS ]

References: [1]Patent: WO2015/75025,2015,A1 .

31
[ 55305-43-6 ]
[ 5345-54-0 ]
[ 102151-33-7 ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: In an Erlenmeyer flask, the aniline (10.0 mmol) was dissolved in an aqueous solution of H4BF4 (50%, 5.0 mL,40.0 mmol) and a saturated solution of sodium nitrite (760 mg, 11.0 mmol) was added dropwise at 0 C. The excess oxidant was removed by the addition of urea. Then, the precipitated diazonium salt was filtered off and dissolved in a small amount of acetone. Diethyl ether was added to the clear solution, causing the precipitation of the arenediazonium tetrafluoroborate, which was filtered off and washed with diethyl ether (3×10.0 mL). The arenediazonium tetrafluoroborate was dried in vacuo (10-3 mbar) for 10 minutes and was then directly used without further purification. (II) General synthesis of N-cyano-N-phenyl-p-methylbenzenesulfonamide(NCTS): (see reference 2) Dry 250 ml Schlenk flask was a solution of phenylurea (10.9 g, 8 mmol) in pyridine (54 mL). The flask was stirred in room temperature water bath. p-Toluenesulfonylchloride (52.8 g, 27.7 mmol) was added potion wise over 5 minutes. The reaction mixture was stirred for another additional 20 minutes and poured into to ice-cooled water (400 mL) with mechanical stirring. Precipitate formed during mechanical stirring was filtered and then washed with water. The crude product was treated with 50 ml of ethanol and precipitated from the same solvent. The precipitate was purified with column chromatography using heptane:EtOAc (15:1) as eluent to yield N-cyano-N-phenyl-p-methylbenzenesulfonamide as colorless solid (16.5 g, 76%). (III) General synthesis of aryl nitriles from the corresponding arenediazonium salts. To a solution of arenediazonium tetrafluoroborate (0.5 mmol) in EtOH (3.0 mL) was added NCTS (272 mg, 1.0 mmol), Pd(OAc)2 (16.8 mg, 0.075 mmol), Ag2CO3 (68.7mg, 0.25 mmol). The mixture was stirred at 58 for 15 h under air atmosphere. Then the reaction mixture was cooled to room temperature and filtered through a pad of celite (1.0 g) and rinsed with CH2Cl2 (10.0 mL). The resulting organic solution was concentrated under reduced pressure and further purified by flash chromatography (SiO2, petroleum ether/EtOAc gradient), yielding the corresponding aryl nitriles.

References: [1]Tetrahedron Letters,2016,vol. 57,p. 1205 - 1209.

32
[ 102151-33-7 ]
3-chloro-N'-hydroxy-4-methoxybenzenecarboximidamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
19%	With hydroxylamine hydrochloride; triethylamine; In ethanol; at 50℃; for 16h;	To a solution of <strong>[102151-33-7]3-chloro-4-methoxybenzonitrile</strong> (500 mg, 3.30 mmol) in 10 ml ethanol was added hydroxylammonium chloride (311 mg, 4.0 mmol) and triethylamine (392 mg, 4.0 mmol) and then the reaction mixture was stirred 16 h at 50 C. After cooling to RT, the solvent was evaporated and the crude - - was solved in ethyl acetate and dichloromethane and extracted with water. The organic phase was dried over magnesium sulfate, filtered and evaporated under vacuum to yield the title compound (124 mg, 19 % of theory). LC-MS (method 3B): RT = 0.79 min, m/z = 201 (M+H)+

References: [1]Patent: WO2016/71216,2016,A1 .Location in patent: Page/Page column 205-206.

33
[ 102151-33-7 ]
tert-butyl 4-{3-[3-(3-chloro-4-methoxyphenyl)-1,2,4-oxadiazol-5-yl]-5-oxo-4,5-dihydropyrazolo[1,5-a]pyrimidin-7-yl}piperidine-1-carboxylate [ No CAS ]

References: [1]Patent: WO2016/71216,2016,A1 .

34
[ 7677-24-9 ]
[ 766-51-8 ]
[ 102151-33-7 ]

References: [1]Journal of the American Chemical Society,2017,vol. 139,p. 2880 - 2883.

35
[ 874-90-8 ]
[ 102151-33-7 ]

References: [1]Chemical Science,2017,vol. 8,p. 7009 - 7013.

Historical Records

Technical Information

• Alkyl Halide Occurrence • Benzylic Oxidation • Birch Reduction • Blaise Reaction • Blanc Chloromethylation • Catalytic Hydrogenation • Complex Metal Hydride Reductions • Friedel-Crafts Reaction • General Reactivity • Grignard Reaction • Hiyama Cross-Coupling Reaction • Hydride Reductions • Hydrogenolysis of Benzyl Ether • Kinetics of Alkyl Halides • Kumada Cross-Coupling Reaction • Preparation of Aldehydes and Ketones • Preparation of Alkylbenzene • Preparation of Amines • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Benzene and Substituted Benzenes • Ritter Reaction • Stille Coupling • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling • Thorpe-Ziegler Reaction • Vilsmeier-Haack Reaction

Related Functional Groups of
[ 102151-33-7 ]

Chlorides

A861924 [13726-21-1]

2-(4-Chloro-3-methoxyphenyl)acetonitrile

Similarity: 0.91

A179159 [2315-81-3]

3-Chloro-4-hydroxybenzonitrile

Similarity: 0.90

A307990 [55877-79-7]

5-Chloro-2-methoxybenzonitrile

Similarity: 0.89

A195936 [127666-99-3]

2-Chloro-4-methoxybenzonitrile

Similarity: 0.84

A258067 [473923-97-6]

3-Chloro-5-hydroxybenzonitrile

Similarity: 0.81

Nitriles

A861924 [13726-21-1]

2-(4-Chloro-3-methoxyphenyl)acetonitrile

Similarity: 0.91

A179159 [2315-81-3]

3-Chloro-4-hydroxybenzonitrile

Similarity: 0.90

A307990 [55877-79-7]

5-Chloro-2-methoxybenzonitrile

Similarity: 0.89

A195936 [127666-99-3]

2-Chloro-4-methoxybenzonitrile

Similarity: 0.84

A258067 [473923-97-6]

3-Chloro-5-hydroxybenzonitrile

Similarity: 0.81

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CAS No.: 102151-33-7

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