[ CAS No. 42872-74-2 ] {[proInfo.proName]}

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2D 3D

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Quality Control of [ 42872-74-2 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 42872-74-2 ]

SDS Specification

Alternatived Products of [ 42872-74-2 ]

Product Details of [ 42872-74-2 ]

CAS No. :	42872-74-2	MDL No. :	MFCD06797818
Formula :	C₈H₆BrN	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	VXUMRYMTYKDWMO-UHFFFAOYSA-N
M.W :	196.04	Pubchem ID :	14004840
Synonyms :

Calculated chemistry of [ 42872-74-2 ] Expand+

Physicochemical Properties

Num. heavy atoms :	10
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.12
Num. rotatable bonds :	0
Num. H-bond acceptors :	1.0
Num. H-bond donors :	0.0
Molar Refractivity :	43.82
TPSA :	23.79 ?2

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.58 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.11
Log Po/w (XLOGP3) :	2.7
Log Po/w (WLOGP) :	2.63
Log Po/w (MLOGP) :	2.52
Log Po/w (SILICOS-IT) :	2.94
Consensus Log Po/w :	2.58

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	2.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-3.2
Solubility :	0.124 mg/ml ; 0.00063 mol/l
Class :	Soluble
Log S (Ali) :	-2.85
Solubility :	0.275 mg/ml ; 0.0014 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.73
Solubility :	0.0368 mg/ml ; 0.000188 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.89

Safety of [ 42872-74-2 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P280	UN#:	N/A
Hazard Statements:	H302+H312+H332	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 42872-74-2 ]

* 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 [ 42872-74-2 ]
Downstream synthetic route of [ 42872-74-2 ]

[ 42872-74-2 ] Synthesis Path-Upstream 1~2

1
[ 42872-74-2 ]
[ 89892-39-7 ]

Yield	Reaction Conditions	Operation in experiment
95%	With N-Bromosuccinimide; dibenzoyl peroxide In tetrachloromethane at 85℃; for 18 h; Inert atmosphere	To a stirred solution of 3-bromo-4-methyl-benzonitrile (2 g, 10.2014 mmol, 100 mass percent) in carbon tetrachloride (20 ml_, 100 mass percent) under argon, was added NBS (2.2 g., 12.2417 mmol, 99 mass percent) and benzoyl peroxide (0.123 g., 0.5101 mmol, 100 mass percent). The mixture was heated to 85°C for 18h. The reaction mass was diluted with water (50 ml) and extracted with ethyl acetate. Organics were washed again with water and brine, dried and evaporated to afford 3-bromo-4-(bromomethyl) benzonitrile (1.2 g, 4.4 mmol, 90 mass percent, 95percent Yield) as an off white solid solid. H NMR (400 MHz, chloroform-c) δ ppm 3.89 - 4.01 (m, 2 H) 6.61 - 6.77 (m, 1 H) 6.92 - 7.07 (m, 2 H) LCMS: RT 1.12-1.49 Min 274 [M+H] ⁺
52.5%	With N-Bromosuccinimide; dibenzoyl peroxide In tetrachloromethaneInert atmosphere; Reflux	The compound 57 (804 mg, 4.04 mmol) was dissolved in carbon tetrachloride (8 mL), and then added with NBS (730 mg, 4.10 mmol) and benzoyl peroxide (7 mg, 0.0289 mmol). The resulting mixture was heated under the protection of nitrogen until reflux occurred, and was stirred overnight. The mixture was cooled to room temperature, filtered to remove insoluble substances and distilled under reduced pressure to remove the solvent, then dissolved in ethyl acetate (30 mL) and respectively washed with water (10 mL) and saturated saline solution (10 mL). After the solvent was removed by means of reduced pressure distillation, the resulting product was purified by using a silica column (200 to 300 mesh silica gel, ethyl acetate/petroleum ether=1/35 for elution) to obtain 3-bromo-4-cyanobenzyl bromide (58) (583 mg), with a yield of 52.5percent.

Reference： [1] Patent: WO2016/113303, 2016, A1, . Location in patent: Page/Page column 41
[2] Journal of the American Chemical Society, 2017, vol. 139, # 2, p. 829 - 835
[3] Journal of the American Chemical Society, 2009, vol. 131, # 39, p. 13908 - 13909
[4] Patent: EP2927219, 2015, A1, . Location in patent: Paragraph 0130; 0132
[5] Journal of Organic Chemistry, 1964, vol. 29, p. 2034 - 2036
[6] Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 21, p. 3821 - 3825
[7] Patent: WO2010/85581, 2010, A1, . Location in patent: Page/Page column 71-72
[8] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 2, p. 644 - 651
[9] Patent: WO2011/22337, 2011, A1, . Location in patent: Page/Page column 104

2
[ 42872-74-2 ]
[ 956218-04-5 ]

Reference： [1] Synlett, 2007, # 14, p. 2179 - 2184

[ 42872-74-2 ] Synthesis Path-Downstream 1~12

1
[ 42872-74-2 ]
[ 183723-09-3 ]

Yield	Reaction Conditions	Operation in experiment
	With Rhodococcus rhodochrous ATCC BAA 870 cobalt nitrile hydratase; In aq. buffer; at 30℃;pH 7.6;Enzymatic reaction;	General procedure: 1800 muL (90%) Tris buffer (50 mM, pH 7.6) and 200 muL(10%) of methanol or acetone. In a 2 mL Eppendorf, NHase (10 mg) was added followed by Trisbuffer. Nitrile substrate (10 mg dissolved in 200 muL methanol or acetone) was added to the 2 mLEppendorf tube. (If an amine group was present on the nitrile substrate a Tris buffer of pH 9 wasused). The reaction mixture was incubated at 30 C on an ESCO Provocell microplateshaker/incubator (Esco Technologies, Halfway House, South Africa) (199 rpm). The reaction wasallowed to proceed for 24 h, 48 h or 5 d, depending on conversion, as monitored by TLC analysis.Ethyl acetate and water were added to the reaction mixture, and after separation, the organic layerwas concentrated under reduced pressure, and the resulting mixture was then purified by silica gelcolumn chromatography eluting with 20% to 90% ethyl acetate/ hexane.

Reference： [1]Journal of Organic Chemistry,1964,vol. 29,p. 2034 - 2036
[2]Molecules,2020,vol. 25

2
[ 42872-74-2 ]
[ 89892-39-7 ]

Yield	Reaction Conditions	Operation in experiment
95%	With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; at 85℃; for 18h;Inert atmosphere;	To a stirred solution of <strong>[42872-74-2]3-bromo-4-methyl-benzonitrile</strong> (2 g, 10.2014 mmol, 100 mass%) in carbon tetrachloride (20 ml_, 100 mass%) under argon, was added NBS (2.2 g., 12.2417 mmol, 99 mass%) and benzoyl peroxide (0.123 g., 0.5101 mmol, 100 mass%). The mixture was heated to 85C for 18h. The reaction mass was diluted with water (50 ml) and extracted with ethyl acetate. Organics were washed again with water and brine, dried and evaporated to afford 3-bromo-4-(bromomethyl) benzonitrile (1.2 g, 4.4 mmol, 90 mass%, 95% Yield) as an off white solid solid. H NMR (400 MHz, chloroform-c) delta ppm 3.89 - 4.01 (m, 2 H) 6.61 - 6.77 (m, 1 H) 6.92 - 7.07 (m, 2 H) LCMS: RT 1.12-1.49 Min 274 [M+H] +
52.5%	With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane;Inert atmosphere; Reflux;	The compound 57 (804 mg, 4.04 mmol) was dissolved in carbon tetrachloride (8 mL), and then added with NBS (730 mg, 4.10 mmol) and benzoyl peroxide (7 mg, 0.0289 mmol). The resulting mixture was heated under the protection of nitrogen until reflux occurred, and was stirred overnight. The mixture was cooled to room temperature, filtered to remove insoluble substances and distilled under reduced pressure to remove the solvent, then dissolved in ethyl acetate (30 mL) and respectively washed with water (10 mL) and saturated saline solution (10 mL). After the solvent was removed by means of reduced pressure distillation, the resulting product was purified by using a silica column (200 to 300 mesh silica gel, ethyl acetate/petroleum ether=1/35 for elution) to obtain 3-bromo-4-cyanobenzyl bromide (58) (583 mg), with a yield of 52.5%.
	With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In chloroform; at 40 - 50℃;Reflux;	5-C. 3-Bromo-4-(bromomethyl)benzonitrile; [00161] A solution of <strong>[42872-74-2]3-bromo-4-methylbenzonitrile</strong> (1 g, 5.10 mmol) in chloroform (20 mL) was heated to 40-50 0C and N-bromosuccinimide (0.953 g, 5.36 mmol) was added in one portion followed by AIBN (8.38 mg, 0.051 mmol). After 1.5 hr. additional AIBN (20mg) was added and the reaction was allowed to stir at 50 0C overnight. Additional AIBN (20mg) and N-bromosuccinimide (l.lg) were added, a reflux condenser was attached and the solution was heated to reflux. After several hours, additional AIBN (20mg) was added and the reaction was allowed to stir at reflux overnight. The reaction was quenched by the addition of water and sat. aq. sodium bicarbonate. The organic phase was separated, concentrated in vacuo and purified by flash column chromatography (12Og silica, eluting with 0%-20% Ethyl Acetate in hexanes) to afford 3-bromo-4-(bromomethyl)benzonitrile as a pale yellow solid (800 mg, 2.88 mmol). 1H NMR (500 MHz, MeOD) delta ppm 4.70 (s, 2H), 7.71 (d, J= 8.0 Hz, IH), 7.73 (d, J= 8.0 Hz, IH), 8.04 (s, IH).

	With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; for 16h;Reflux; Inert atmosphere;	General procedure: To 2-bromo-3-methylbenzoic acid (21, 159 g, 739 mmol) in dichloromethane (1000 mL) was added triethylamine (TEA, 119.7 mL, 813 mmol, 1.1 equiv) followed by iso-butyl chloroformate (101.5 mL, 813 mmol, 1.1 equiv) in dichloromethane (DCM, 200 mL) at 0 C over 10 min. Concentrated ammonia water (323 mL) was then added at 0 C over 2 min. The reaction mixture was poured into water (200 mL), cooled to rt and filtered. The solid was washed with water (2 × 300 mL), 0.5 N HCl (2 × 150 mL) and dried to give the amide as a solid (120 g, yield 76%). To the solution of the amide obtained (50 g, 233.6 mmol) in DMF (300 mL) was added 2,4,6-trichloro-1,3,5-triazine (64.6 g, 350.4 mmol, 1.5 equiv) dropwise at 0 C and the reaction was stirred at rt overnight. To the reaction was added 600 mL of water and the reaction was stirred for 30 min. All insoluble was removed by filtration and the solid was triturated with ethyl acetate (EA, 3 × 100 mL) for 40 min and filtered. The filtrate was washed with saturated sodium carbonate (3 × 200 mL), saturated sodium chloride (200 mL) and dried over anhydrous sodium sulfate.The solvent was removed under reduced pressure to give 22 as a solid (42 g, yield 87.3%). To a solution of 22 (20 g, 102.2 mmol, 1 equiv) in CCl4 (200 mL) was added NBS (18.2 g, 102.0 mmol, 1.0 equiv), Bz2O2 (0.15 g, 0.6 mmol, 0.006 equiv). The reaction was refluxed overnight under N2, cooled and filtered. The filtrate was crystallized at 0 C to provide the brominated intermediate (15 g, yield 53.6%). To a solution of the brominated intermediate (90 g, 327.3 mmol) in DMF (760 ml) was added KOAc (38.6 g, 393.1 mmol, 1.2 equiv). The reaction mixture was stirred at 80 C for 1 h, cooled and water (1 L) was added. The mixture was extracted with EA (1 L). The organic layer was washed with 0.5 N HCl (3 ×200 mL), 2% NaHCO3 (200 mL) and dried over anhydrous sodium sulfate. The solvent was removed to give 23 as a yellow solid (77.3 g, yield 92.9%). 1H NMR of 23 (500 MHz, CDCl3): delta 2.16 (s, 3H), 5.21 (s, 2H), 7.43-7.46 (t, 1H,), 7.63 (m, 2H) ppm. To a solution of 23 (20 g, 78.8 mmol) in 1,4-dioxane (400 mL) was added bis(pinacolato)diboron (30 g, 118.1 mmol, 1.5 equiv) and KOAc (33.2 g, 338.1 mmol, 4.3 equiv). After being de-gassed and backfilled with nitrogen, Pd(dppf)Cl2 (3.2 g, 3.935 mmol, 0.05 equiv) was added. The reaction was refluxed overnight under nitrogen, cooled and filtered. The filtrate was concentrated and the residue was purified by silica gel column chromatography eluted with petroleum ether (PE)/EA = 5:1 to give 24 as red oil (29 g, crude yield 100% with 80% purity). 1H NMR of 24 (500 MHz, DMSO-d6): delta 1.42 (s, 12H), 2.20 (s, 3H), 5.25 (s, 2H), 7.44-7.49 (t, 1H), 7.57-7.64 (m, 2H) ppm. To a solution of 24 (29 g) in MeOH (100 mL) was added a solution of NaOH in MeOH (7.0 g/130 mL, 175.8 mmol, 2.3 equiv) and the reaction was stirred for 2 h at rt. The reaction mixture was concentrated under vacuum and the residue was dissolved in THF (150 mL) and 2 N HCl (138 mL, 69 mmol, 0.9 equiv). The reaction was stirred at rt for 50 min, concentrated and filtered. The solid was washed with water (3 × 20 mL) and petroleum ether (3 × 20 mL) to provide 25 (7.6 g, yield 62%). 1H NMR of 25 (500 MHz, DMSO-d6): delta 5.05 (s, 2H), 7.63-7.68 (t, 1H), 7.73-7.81 (m, 2H) ppm. To Raney Ni (0.849 g, 14.5 mmol, 2.3 equiv) in formic acid (10 mL) and water (2 mL) was added 25 (1 g, 6.29 mmol) at rt. The reaction was stirred at 100 C for 1 h, cooled and then filtered. The solvent was removed to give a solid that was purified by silica gel column chromatography eluted with CH2Cl2 to give 26 as a solid (0.714 g, yield 70%). 1H NMR of 26 (500 MHz, CDCl3): delta 10.03 (s, 1H), 8.08 (s, 1H), 7.86 (t, 1H), 7.63-7.71 (m, 2H), 5.20 (s, 2H) ppm. To a mixture of HCOOH (116.2 g, 10.0 equiv) and TEA (102.2 g, 4.0 equiv) were added 26 (40.9 g, 252.5 mmol) and 2,2-dimethyl-1,3-dioxane-4,6-dione (43.7 g, 1.2 equiv). The resulting mixture was refluxed for 15 h and cooled to rt. Hydrochloric acid (2 N, 320 mL) was added into the mixture that was then extracted with ethyl acetate twice (2 × 250 mL). The combined organic layer was washed with 2 N HCl (160 mL) and rotary evaporated to give the crude product that was recrystallized from DMF and 2 N HCl (34:204 mL) providing compound 1 as a white solid (15.6 g, yield 30%). An additional recrystallization from DMF and 2 N HCl (16:96 mL) was performed to give high purity product (12.9 g).
	With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane;Reflux;	To a solution of <strong>[42872-74-2]3-bromo-4-methylbenzonitrile</strong> (276 g, 1.41 mol) in CCl4 (3.0 L) was added benzoyl peroxide (BPO, 3.0 g) and NBS (298.0 g, 1.65 mol). The mixture was stirred at refluxing temperature overnight. The mixture was cooled and diluted with DCM, washed with water and concentrated in vacuum to give 3-bromo- 4-(bromomethyl)benzonitrile (415 g) as a crude product which was used for next step directly without further purification.

Reference： [1]Patent: WO2016/113303,2016,A1 .Location in patent: Page/Page column 41
[2]Journal of the American Chemical Society,2017,vol. 139,p. 829 - 835
[3]Journal of the American Chemical Society,2009,vol. 131,p. 13908 - 13909
[4]Patent: EP2927219,2015,A1 .Location in patent: Paragraph 0130; 0132
[5]Organic Letters,2020,vol. 22,p. 1624 - 1627
[6]Journal of Organic Chemistry,1964,vol. 29,p. 2034 - 2036
[7]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 3821 - 3825
[8]Patent: WO2010/85581,2010,A1 .Location in patent: Page/Page column 71-72
[9]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 644 - 651
[10]Patent: WO2011/22337,2011,A1 .Location in patent: Page/Page column 104

3
[ 42872-74-2 ]
[ 98-86-2 ]
α-(5-cyano-2-methylphenyl)acetophenone [ No CAS ]

Reference： [1]Organic Letters,2006,vol. 8,p. 645 - 647

4
[ 121-43-7 ]
[ 42872-74-2 ]
[ 867333-43-5 ]

Yield	Reaction Conditions	Operation in experiment
53%		Step 1 : Synthesis of 5-cyano-2-methylphenylboronic acid First, 9.5 g (50 mmol) of <strong>[42872-74-2]3-bromo-4-methylbenzonitrile</strong> was put into a 500 mL three-neck flask, and the atmosphere in the flask was replaced with nitrogen. Then, 250 mL of tetrahydrofuran (THF) was added, and the mixture was stirred at -78 C for 30 minutes. Into this mixed solution, 34 mL (55 mmol) of a 1.63M hexane solution of -butyllithium (-BuLi) was dropped, followed by stirring at -78 C for 1.5 hours. After that, 7.3 mL (65 mmol) of trimethyl borate was added to the mixture and this solution was stirred for 20 hours while the temperature was raised to room temperature. To this solution was added 100 mL of 1M hydrochloric acid and stirring was performed for 30 minutes. The obtained mixture was separated to an aqueous layer and an organic layer, and the aqueous layer was subjected to extraction with ethyl acetate. The organic layer and a solution of the extract were combined, and washed with saturated saline. Anhydrous magnesium sulfate was added to the obtained solution for drying. The obtained mixture was subjected to gravity filtration, and the filtrate was concentrated to give a solid. This solid was washed with toluene and hexane, so that 4.3 g of a white solid was obtained in a yield of 53 %. The obtained white solid was identified as 5-cyano-2-methylphenylboronic acid by nuclear magnetic resonance ( MR) spectroscopy. The synthesis scheme of Step 1 is shown in (a-10) below.

Reference： [1]Patent: WO2016/203350,2016,A1 .Location in patent: Paragraph 1195
[2]Journal of the American Chemical Society,2002,vol. 124,p. 9014 - 9015

5
[ 42872-74-2 ]
[ 956218-04-5 ]

Reference： [1]Synlett,2007,p. 2179 - 2184

6
[ 42872-74-2 ]
C₁₀H₇NO₂ [ No CAS ]

Reference： [1]Synlett,2007,p. 2179 - 2184

7
[ 42872-74-2 ]
[ 450839-99-3 ]