[ CAS No. 36057-46-2 ] {[proInfo.proName]}

Name: 36057-46-2|5-Bromo-3-methoxypyridine 2-carbonitrile|97%
Brand: Ambeed
SKU: A479301
Price: 36.0 USD
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Inaccessible (Haz class 6.1), International	USD 150+
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Quality Control of [ 36057-46-2 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 36057-46-2 ]

SDS Specification

Alternatived Products of [ 36057-46-2 ]

Product Details of [ 36057-46-2 ]

CAS No. :	36057-46-2	MDL No. :	MFCD11857636
Formula :	C₇H₅BrN₂O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	WIRVBLLSXJUOHZ-UHFFFAOYSA-N
M.W :	213.03	Pubchem ID :	44558090
Synonyms :

Calculated chemistry of [ 36057-46-2 ]

Physicochemical Properties

Num. heavy atoms :	11
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.14
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	43.14
TPSA :	45.91 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) :	-6.48 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.89
Log Po/w (XLOGP3) :	1.57
Log Po/w (WLOGP) :	1.72
Log Po/w (MLOGP) :	0.28
Log Po/w (SILICOS-IT) :	1.98
Consensus Log Po/w :	1.49

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.49
Solubility :	0.693 mg/ml ; 0.00325 mol/l
Class :	Soluble
Log S (Ali) :	-2.14
Solubility :	1.53 mg/ml ; 0.00717 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.1
Solubility :	0.17 mg/ml ; 0.000798 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.0

Safety of [ 36057-46-2 ]

Signal Word:	Danger	Class:	6.1
Precautionary Statements:	P264-P270-P301+P310+P330-P405-P501	UN#:	2811
Hazard Statements:	H301	Packing Group:	Ⅲ
GHS Pictogram:

Application In Synthesis of [ 36057-46-2 ]

* 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 [ 36057-46-2 ]
Downstream synthetic route of [ 36057-46-2 ]

[ 36057-46-2 ] Synthesis Path-Upstream 1~3

1
[ 886373-28-0 ]
[ 124-41-4 ]
[ 36057-46-2 ]

Yield	Reaction Conditions	Operation in experiment
95%	at 70℃; for 3 h; Inert atmosphere	5-bromo-3-methoxypicolinonitrile To a solution of 5-bromo-3-fluoropyridine-2-carbonitrile (2.00 g, 9.93 mmol) in THF (80 mL) was added sodium methoxide (2.68 g, 49.59 mmol) at room temperature. The resulting solution was then stirred for 3 h at 70° C. When the reaction was done, the pH value of the reaction mixture was adjusted to 7 with hydrogen chloride solution (3 M). The resulting mixture was extracted with ethyl acetate (100 mL*3). The organic phases were combined, washed with brine and dried over sodium sulfate. The solvent was removed under reduced pressure to yield 5-bromo-3-methoxypyridine-2-carbonitrile as a brown solid (2.00 g, 95percent). MS: m/z=213.0 [M+H]⁺.
75%	at 20℃; for 2 h;	Sodium methoxide (9.7 g, 0.18 mol) in methanol (50 ml) was added dropwise to a suspension of 5-bromo-3-fluoropyridine-2-carbonitrile (30 g, 0.15 mol) in methanol (150 ml) at room temperature. After completion of the dropwise addition, the mixture was reacted for 2 hours while the reaction solution became clear. A small amount of glacial acetic acid was added to the solution to adjust the pH to between 7 and 8, and ice water (300 ml) was added. The reaction solution was concentrated until a solid precipitated, and allowed to stand and cool for 2 hours so that the solid precipitated more thoroughly. The precipitated solid was filtered off and the filter cake was washed with water, collected and air dried at room temperature to obtain 5-bromo-3-methoxypyridine-2-carbonitrile as a white solid (24 g, 75percent yield).
69%	for 18 h; Heating / reflux	5-Bromo-2-cyano-3-methoxy-pyridine: Mix sodium methoxide (141 mg, 2.61 mmol) and 5-bromo-2- cyano-3-fluoro-pyridine (105 mg, 0.52 mmol) in THF (5 mL) and reflux for 18 h. Add pH 7 phosphate buffer solution and extract with EtOAc. Dry the EtOAc extracts over MgSO₄. Remove the drying agent and evaporate the filtrate. Purify the crude product using a silica gel chromatography and elute with EtOAc/hexane (0 to 30 percent) to give 77 mg (69percent yield) of S-bromo^-cyano-S-methoxy-pyridine.

Reference： [1] Patent: US2016/376283, 2016, A1, . Location in patent: Paragraph 1219; 1220
[2] Patent: EP3275864, 2018, A1, . Location in patent: Paragraph 0032; 0038; 0044; 0050; 0056; 0062
[3] Patent: WO2007/87488, 2007, A2, . Location in patent: Page/Page column 24

2
[ 573675-25-9 ]
[ 124-41-4 ]
[ 36057-46-2 ]

Yield	Reaction Conditions	Operation in experiment
70%	at 0℃; for 8 h; Reflux	To a stirred solution of 5-bromo-2-cyano-3-nitropyridene (5 g, 0.021 mol) in MeOH (50 mL) at 0°C was added 0.5M sodium methoxide (40 mL) and the RM was heated to reflux and stirred for 8 hr. Afterreaction completion the mixture was concentrated under reduced pressure to give crude 5-bromo-3-methoxypicolinonitrile. The crude was purified by CC (0-15percent EtOAc in PE) and concentrated at below45°C to give 5-bromo-3-methoxypicolinonitrile (3.4 g, 70percent), as a solid.

Reference： [1] Patent: WO2015/158427, 2015, A1, . Location in patent: Page/Page column 88

3
[ 67-56-1 ]
[ 573675-25-9 ]
[ 36057-46-2 ]

Yield	Reaction Conditions	Operation in experiment
78%	for 8 h; Reflux	To a solution of 5-bromo-3-nitro-pyridine-2-carbo-nitrile (2 g, 8.8 mmol) in MeOH (25 ml), 0.5 M NaOMe (in MeOH, 15 ml) was added at room temperature. The reaction mixture was heated to reflux and stirred for 8 hours at this temperature. After the reaction completion, the reaction mixture was concentrated under reduced pressure. The residue was purified via column chromatography (Ethyl acetate : n-Hexane = 1 : 4) and the target compound of 1.46 g was obtained. (78percent yield) ¹H NMR (300 MHz, CDCl₃): δ 8.318 (d, J= 1.5Hz, 1H), 7.523 (d, J= 1.5Hz, 1H), 3.973 (s, 3H), MS: m/z 215 [M+1]
78%	for 8 h; Reflux	To a solution of 5-bromo-3-nitro-pyridine-2-carbonitrile (2 g, 8.8 mmol) in MeOH (25 ml), 0.5 M NaOMe (in MeOH, 15 ml) was added at room temperature. The reaction mixture was heated to reflux and stirred for 8 hours at this temperature. After the reaction completion, the reaction mixture was concentrated under reduced pressure. The residue was purified via column chromatography (Ethyl acetate : n-Hexane = 1 : 4) and the target compound of 1.46 g was obtained. (78percentyield)

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 14, p. 3142 - 3145
[2] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 14, p. 3142 - 3145

[ 36057-46-2 ] Synthesis Path-Downstream 1~60

2
[ 886373-28-0 ]
[ 124-41-4 ]
[ 36057-46-2 ]

Yield	Reaction Conditions	Operation in experiment
95%	In tetrahydrofuran; at 70℃; for 3.0h;Inert atmosphere;	5-bromo-3-methoxypicolinonitrile To a solution of 5-bromo-3-fluoropyridine-2-carbonitrile (2.00 g, 9.93 mmol) in THF (80 mL) was added sodium methoxide (2.68 g, 49.59 mmol) at room temperature. The resulting solution was then stirred for 3 h at 70 C. When the reaction was done, the pH value of the reaction mixture was adjusted to 7 with hydrogen chloride solution (3 M). The resulting mixture was extracted with ethyl acetate (100 mL*3). The organic phases were combined, washed with brine and dried over sodium sulfate. The solvent was removed under reduced pressure to yield 5-bromo-3-methoxypyridine-2-carbonitrile as a brown solid (2.00 g, 95%). MS: m/z=213.0 [M+H]+.
75%	In methanol; at 20℃; for 2.0h;	Sodium methoxide (9.7 g, 0.18 mol) in methanol (50 ml) was added dropwise to a suspension of 5-bromo-3-fluoropyridine-2-carbonitrile (30 g, 0.15 mol) in methanol (150 ml) at room temperature. After completion of the dropwise addition, the mixture was reacted for 2 hours while the reaction solution became clear. A small amount of glacial acetic acid was added to the solution to adjust the pH to between 7 and 8, and ice water (300 ml) was added. The reaction solution was concentrated until a solid precipitated, and allowed to stand and cool for 2 hours so that the solid precipitated more thoroughly. The precipitated solid was filtered off and the filter cake was washed with water, collected and air dried at room temperature to obtain 5-bromo-3-methoxypyridine-2-carbonitrile as a white solid (24 g, 75% yield).
69%	In tetrahydrofuran; for 18.0h;Heating / reflux;	5-Bromo-2-cyano-3-methoxy-pyridine: Mix sodium methoxide (141 mg, 2.61 mmol) and 5-bromo-2- cyano-3-fluoro-pyridine (105 mg, 0.52 mmol) in THF (5 mL) and reflux for 18 h. Add pH 7 phosphate buffer solution and extract with EtOAc. Dry the EtOAc extracts over MgSO4. Remove the drying agent and evaporate the filtrate. Purify the crude product using a silica gel chromatography and elute with EtOAc/hexane (0 to 30 %) to give 77 mg (69% yield) of S-bromo^-cyano-S-methoxy-pyridine.

Reference： [1]Patent: US2016/376283,2016,A1 .Location in patent: Paragraph 1219; 1220
[2]Patent: EP3275864,2018,A1 .Location in patent: Paragraph 0032; 0038; 0044; 0050; 0056; 0062
[3]Patent: WO2007/87488,2007,A2 .Location in patent: Page/Page column 24

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[ 36057-46-2 ]
[ 1615720-26-7 ]