[ CAS No. 1223434-15-8 ] {[proInfo.proName]}

Name: 1223434-15-8|Methyl 4-bromo-2-cyanobenzoate|95%
Brand: Ambeed
SKU: A161103
Price: 30.0 USD
Availability: InStock
Rating: 95 (29 reviews)

,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

DV 2D 3D

3d Animation Molecule Structure of 1223434-15-8

Structure of 1223434-15-8 * Storage: {[proInfo.prStorage]}

Please Login or Create an Account to: See VIP prices and availability

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

* Shipping: {[proInfo.prShipping]}

For Research Only 120K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 1223434-15-8 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 1223434-15-8 ]

SDS Specification

Alternatived Products of [ 1223434-15-8 ]

Product Details of [ 1223434-15-8 ]

CAS No. :	1223434-15-8	MDL No. :	MFCD18398741
Formula :	C₉H₆BrNO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	APAVVMSHHACFQV-UHFFFAOYSA-N
M.W :	240.05	Pubchem ID :	58484706
Synonyms :

Calculated chemistry of [ 1223434-15-8 ] Expand+

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.11
Num. rotatable bonds :	2
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	50.14
TPSA :	50.09 Å²

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) :	-6.22 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.14
Log Po/w (XLOGP3) :	2.18
Log Po/w (WLOGP) :	2.11
Log Po/w (MLOGP) :	2.0
Log Po/w (SILICOS-IT) :	2.37
Consensus Log Po/w :	2.16

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.91
Solubility :	0.294 mg/ml ; 0.00123 mol/l
Class :	Soluble
Log S (Ali) :	-2.87
Solubility :	0.327 mg/ml ; 0.00136 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.42
Solubility :	0.0915 mg/ml ; 0.000381 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.04

Safety of [ 1223434-15-8 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 1223434-15-8 ]

* 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 [ 1223434-15-8 ]
Downstream synthetic route of [ 1223434-15-8 ]

[ 1223434-15-8 ] Synthesis Path-Upstream 1~3

1
[ 1093418-75-7 ]
[ 1223434-15-8 ]

Yield	Reaction Conditions	Operation in experiment
90%	at 60℃; for 2 h;	Into a 250-mE round-bottom flask, was placed methyl 4-bromo-2-iodobenzoate (5.8 g, 17.01 mmol, 1.00 equiv), NMP (60 mE), CuCN (1.82 g, 20.45 mmol, 1.20 equiv). The resulting solution was stirred for 2 hours at 60° C. in an oil bath. The resulting solution was extracted with ethyl acetate (50 mEx2) and the organic layers combined. The resulting mixture was washed with Fe504 (aq.) (50 mEx2). The mixture was dried over anhydrous sodium sulfate. The residue was applied onto a silica gel colunm with ethyl acetate/petroleum ether (1/3). This resulted in 3.68 g (90percent) of methyl 4-bromo-2-cyanobenzoate as a white solid.
2.39 g	at 60℃; for 1 h;	[0363] Preparation Example 75: Preparation of methyl 4-bromo-2-cyanobenzoate[0364][0365] To a mixture of methyl 4-bromo-2-iodobenzoate (3.52 g) described in Preparation Example 74 and coppercyanide (1.16 g) was added N-methylpyrrolidone (21 mL), and the mixture was stirred at 60°C for 1 hr. The reactionmixture was cooled, a solution of saturated aqueous ammonium chloride solution and aqueous ammonia (1:1) wasadded, and the mixture was extracted with ethyl acetate. The organic layer was washed with a solution of saturatedaqueous ammonium chloride solution and aqueous ammonia (1:1), saturated aqueous ammonium chloride solution,and saturated brine. The organic layer was dried over sodium sulfate, and the solvent was evaporated to give the titlecompound (2.39 g).MS (ESI) m/z:240(M+H)+.

Reference： [1] Patent: US2018/215731, 2018, A1, . Location in patent: Paragraph 1118; 1120
[2] Patent: EP2565182, 2013, A1, . Location in patent: Paragraph 0363; 0364; 0365

2
[ 135484-83-2 ]
[ 1223434-15-8 ]

Yield	Reaction Conditions	Operation in experiment
980 mg	Stage #1: With hydrogenchloride; sodium nitrite In water for 1 h; Cooling with ice Stage #2: With potassium cyanide In water; ethyl acetate for 1 h; Cooling with ice	To an ice-cooled mixture of Compound I (1.5 g) and 2N hydrochloric acid was added a mixture of sodium nitrite (540 mg) and water (6.5 mL), and the mixture was stirred for 1 hour. The reaction mixture was neutralized by the addition of sodium carbonate. Then, to an ice-cooled mixture of copper cyanide (759 mg), potassium cyanide (637 mg), ethyl acetate (8 mL) and water (4 mL) was added the reaction mixture of Compound I which was prepared above, and the mixture was stirred for 1 hour. The reaction mixture was filtered through Celite, and to the filtrate was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate = 10/0 to 8/2) to give Compound II (980 mg).

Reference： [1] Patent: EP2612848, 2013, A1, . Location in patent: Paragraph 0437; 0438; 0439

3
[ 135484-83-2 ]
[ 1223434-15-8 ]

Reference： [1] Patent: EP2565182, 2013, A1,
[2] Patent: US2018/215731, 2018, A1,

[ 1223434-15-8 ] Synthesis Path-Downstream 1~20

1
[ 135484-83-2 ]
[ 1223434-15-8 ]

Reference： [1]Patent: EP2565182,2013,A1
[2]Patent: US2018/215731,2018,A1

2
[ 1093418-75-7 ]
copper(l) cyanide [ No CAS ]
[ 1223434-15-8 ]

Yield	Reaction Conditions	Operation in experiment
90%	In 1-methyl-pyrrolidin-2-one; at 60℃; for 2h;	Into a 250-mE round-bottom flask, was placed methyl 4-bromo-2-iodobenzoate (5.8 g, 17.01 mmol, 1.00 equiv), NMP (60 mE), CuCN (1.82 g, 20.45 mmol, 1.20 equiv). The resulting solution was stirred for 2 hours at 60 C. in an oil bath. The resulting solution was extracted with ethyl acetate (50 mEx2) and the organic layers combined. The resulting mixture was washed with Fe504 (aq.) (50 mEx2). The mixture was dried over anhydrous sodium sulfate. The residue was applied onto a silica gel colunm with ethyl acetate/petroleum ether (1/3). This resulted in 3.68 g (90%) of methyl 4-bromo-2-cyanobenzoate as a white solid.
2.39 g	In 1-methyl-pyrrolidin-2-one; at 60℃; for 1h;	[0363] Preparation Example 75: Preparation of methyl 4-bromo-2-cyanobenzoate[0364][0365] To a mixture of methyl 4-bromo-2-iodobenzoate (3.52 g) described in Preparation Example 74 and coppercyanide (1.16 g) was added N-methylpyrrolidone (21 mL), and the mixture was stirred at 60C for 1 hr. The reactionmixture was cooled, a solution of saturated aqueous ammonium chloride solution and aqueous ammonia (1:1) wasadded, and the mixture was extracted with ethyl acetate. The organic layer was washed with a solution of saturatedaqueous ammonium chloride solution and aqueous ammonia (1:1), saturated aqueous ammonium chloride solution,and saturated brine. The organic layer was dried over sodium sulfate, and the solvent was evaporated to give the titlecompound (2.39 g).MS (ESI) m/z:240(M+H)+.

Reference： [1]Patent: US2018/215731,2018,A1 .Location in patent: Paragraph 1118; 1120
[2]Patent: EP2565182,2013,A1 .Location in patent: Paragraph 0363; 0364; 0365

3
[ 1223434-15-8 ]
[ 1223434-16-9 ]

Yield	Reaction Conditions	Operation in experiment
7.97 g		[0366] Preparation Example 76: Preparation of 4-bromo-2-cyanobenzoic acid[0367][0368] Methyl 4-bromo-2-cyanobenzoate (8.53 g) described in Preparation Example 75 was dissolved in dimethoxyethane(140 mL), a solution of lithium hydroxide 1 hydrate (2.24 g) in water (54 mL) was added dropwise underice-cooling, and the mixture was stirred at the same temperature for 30 min. To the reaction mixture was added dropwise1N hydrochloric acid (60 mL) under ice-cooling, saturated brine was added, and the mixture was extracted with ethylacetate. The organic layer was washed with saturated brine, dried over sodium sulfate, and the solvent was evaporatedto give the title compound (7.97 g).MS (ESI) m/z:226(M+H)+
808 mg	With water; lithium hydroxide; In methanol; at 20℃; for 4h;	A mixture of Compound II (980 mg), 2N aqueous lithium hydroxide solution (6.1 mL) and methanol (18 mL) was stirred at room temperature for 4 hours. The reaction mixture was concentrated under reduced pressure, and to the residue was added 1N aqueous sodium hydroxide solution, and the mixture was extracted with ethyl acetate. The aqueous layer was acidified with 4N hydrochloric acid, and then extracted with chloroform. The chloroform layer was dried over sodium sulfate, and then concentrated under reduced pressure to give Compound III (808 mg).

Reference： [1]Patent: EP2565182,2013,A1 .Location in patent: Paragraph 0366; 0367; 0368
[2]Patent: EP2612848,2013,A1 .Location in patent: Paragraph 0437; 0438; 0440

4
[ 135484-83-2 ]
copper(l) cyanide [ No CAS ]
[ 1223434-15-8 ]

Yield	Reaction Conditions	Operation in experiment
980 mg		To an ice-cooled mixture of Compound I (1.5 g) and 2N hydrochloric acid was added a mixture of sodium nitrite (540 mg) and water (6.5 mL), and the mixture was stirred for 1 hour. The reaction mixture was neutralized by the addition of sodium carbonate. Then, to an ice-cooled mixture of copper cyanide (759 mg), potassium cyanide (637 mg), ethyl acetate (8 mL) and water (4 mL) was added the reaction mixture of Compound I which was prepared above, and the mixture was stirred for 1 hour. The reaction mixture was filtered through Celite, and to the filtrate was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate = 10/0 to 8/2) to give Compound II (980 mg).

Reference： [1]Patent: EP2612848,2013,A1 .Location in patent: Paragraph 0437; 0438; 0439

5
[ 1223434-15-8 ]
C₁₈H₁₉BrN₂O₂ [ No CAS ]

Reference： [1]Patent: EP2612848,2013,A1

6
[ 1223434-15-8 ]
C₁₁H₇NO₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 94 - 102

7
[ 1223434-15-8 ]
C₁₆H₁₁NO₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 94 - 102

8
[ 1223434-15-8 ]
C₁₅H₉NO₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 94 - 102

9
[ 1223434-15-8 ]
C₂₀H₁₈N₂O₄ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 94 - 102

10
[ 1223434-15-8 ]
C₁₉H₁₇N₃O₄ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 94 - 102

11
[ 1223434-15-8 ]
[ 1066-54-2 ]
C₁₄H₁₅NO₂Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In tetrahydrofuran; at 60℃; for 5h;	General procedure: A mixture of V-01 (922 mg, 4.292 mmol), ethynyltrimethylsilane (506 mg, 5.153 mmol), Pd(PPh3)2Cl2 (150 mg, 0.214 mmol), CuI (25 mg, 0.131 mmol), TEA (1.73 g, 17.16 mmol) was dissolved in anhydrous THF (20 mL). The mixture was stirred at 60 for 5 h. The solvent was removed under reduced pressure. The residue was partitioned between ethyl ether and water. The organic layer was washed with water and brine, dried over anhydrous Na2SO4, filtered and then the filtrate was concentrated in vacuo. The residue was purified by silica gel chromatography with PE/EA (50/1-20/1) to give 0.9 g (90.4%) of V-13 as a brown oil.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 94 - 102

12
[ 1223434-15-8 ]
( 1S,4S,5R)-5-[[3-(2,6-dichlorophenyl)-5-(1-fluorocyclopropyl)-1,2-oxazol-4-yl]methoxy]-2-azabicyclo[2.2.1]heptane [ No CAS ]
methyl 2-cyano-4-[(1S,4S,5R)-5-[[3-(2,6-dichlorophenyl)-5-(1-fluorocyclopropyl)-1,2-oxazol-4-yl]methoxy]-2-azabicyclo[2.2.1]heptan-2-yl]benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54%	With potassium carbonate; In dimethyl sulfoxide; at 110℃;	To a 50 mL round-bottorn flask was added (1 S,4S,5R)-5-[[3-(2,6-dichlorophenyl)-5-( 1-Huorocyclopropyl)-1 ,2-oxazol-4-yl]methoxy ]-2-azabicyclo[2.2.1 ]heptane 24d (120 mg,0.30 mmol, 1.0 equiv.), methyl4-bromo-2-cyanobenzoate (55 mg, 0.23 mmol, 1.0 equiv.),pota;;;sium carbonate (83 mg, 0.60 mmol, 2.0 equiv.), and DMSO (1 mL). The resultingrnix ture was stirred at ll 0C overnight After cooling to room temperature, the mixture Vas30 diluted '.vith of ethyl acetate and added with H20. The pH value of the solution '.Vas adjusted to 6 using a lM hydrogen chloride aqueous solution. The aqueous mixture was extracted withethyl acetate (1 00 mL x 2). l11e combined organic extracts were ·washed with brine (50 mL x4), dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue waspurified by silica gel column chromatography eluting with ethyl acetate/petroleum ether (1 :3)5 to give methyl 2-cyano-4-[( l S,4S,5R)-5-UJ-(2,6-dichloropheny l)-5-(J -iluorocyclopropy l)L2-oxazol-4-yl]methoxy ]-2-azabicyclo[2.2.1]heptan-2-yl]benzoate 123a (90 mg, 54~~) as anoff-white solid.

Reference： [1]Patent: WO2018/39386,2018,A1 .Location in patent: Page/Page column 258; 259

13
[ 1223434-15-8 ]
rac-N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4-methylene-1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yl)piperazin-1-yl)methyl)piperidin-1-yl)benzamide [ No CAS ]