[ CAS No. 22282-96-8 ] {[proInfo.proName]}

Name: 22282-96-8|2-Bromo-6-methyl-5-nitropyridine|98%
Brand: Ambeed
SKU: A143446
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3d Animation Molecule Structure of 22282-96-8

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Quality Control of [ 22282-96-8 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 22282-96-8 ]

SDS Specification

Alternatived Products of [ 22282-96-8 ]

Product Details of [ 22282-96-8 ]

CAS No. :	22282-96-8	MDL No. :	MFCD03095219
Formula :	C₆H₅BrN₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	PCNVKBBKROTUNS-UHFFFAOYSA-N
M.W :	217.02	Pubchem ID :	24728014
Synonyms :

Calculated chemistry of [ 22282-96-8 ]

Physicochemical Properties

Num. heavy atoms :	11
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.17
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	45.72
TPSA :	58.71 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) :	-6.13 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.55
Log Po/w (XLOGP3) :	2.11
Log Po/w (WLOGP) :	2.06
Log Po/w (MLOGP) :	0.39
Log Po/w (SILICOS-IT) :	0.34
Consensus Log Po/w :	1.29

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.85
Solubility :	0.305 mg/ml ; 0.0014 mol/l
Class :	Soluble
Log S (Ali) :	-2.97
Solubility :	0.231 mg/ml ; 0.00106 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.65
Solubility :	0.484 mg/ml ; 0.00223 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	3.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.2

Safety of [ 22282-96-8 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P280-P305+P351+P338-P310	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 22282-96-8 ]

* 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 [ 22282-96-8 ]
Downstream synthetic route of [ 22282-96-8 ]

[ 22282-96-8 ] Synthesis Path-Upstream 1~5

1
[ 28489-45-4 ]
[ 22282-96-8 ]

Reference： [1] Journal of the American Chemical Society, 1955, vol. 77, p. 6053

2
[ 28489-45-4 ]
[ 22282-96-8 ]

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 5, p. 795 - 798

3
[ 22282-96-8 ]
[ 126325-47-1 ]

Yield	Reaction Conditions	Operation in experiment
86.7%	With hydrogenchloride; iron; ammonium chloride In ethanol; water at 65 - 80℃; for 3 h;	A suspension of 6-bromo-2-methyl-3-nitropyridine (XIV) (250 g, 1.15 mol, 1.00 eq) and NH4C1 (300 g, 5.61 mol, 4.88 eq) in EtOH (3.50 L) and water (150 mL) was heated with stirring to 65°C. To this mixture was added Fe (130 g, 2.33 mol, 2.02 eq) and HC1 (15.3 g, 419 mmol, 0.36 eq). The suspension was then heated to 80°C for another 3 h. The reaction was cooled to 25°C and filtered through a plug of Celite. The filtrate was concentrated under reduced pressure to yield a residue that was taken up in EtOAc (1 L x 3) and washed with brine. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to give 6-bromo-2-methylpyridin-3-amine (XV) as brown solid (373 g, 1.99 mol, 86.7percent yield) which was used for the next step without any purification. ‘H NMR (DM50-cl6, 400 MHz) ppm 6.01 (dd, J= 2.3, 7.9 Hz, 2H), 7.03 (d, J= 8.2 Hz, 1H); ESIMS found for C6H7BrN2 mlz 186.8 (M+H).
86.7%	With hydrogenchloride; iron; ammonium chloride In ethanol; water at 65 - 80℃; for 3 h;	A suspension of 6-bromo-2-methyl-3-nitropyridine (XIV) (250 g, 1.15 mol, 1.00 eq) and NH₄C1 (300 g, 5.61 mol, 4.88 eq) in EtOH (3.50 L) and water (150 mL) was heated with stirring to 65°C. To this mixture was added Fe (130 g, 2.33 mol, 2.02 eq) and HC1 (15.3 g, 419 mmol, 0.36 eq). The suspension was then heated to 80°C for another 3 h. The reaction was cooled to 25°C and filtered through a plug of Celite. The filtrate was concentrated under reduced pressure to yield a residue that was taken up in EtOAc (1 L x 3) and washed with brine. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to give 6-bromo-2-methylpyridin-3-amine (XV) as brown solid (373 g, 1.99 mol, 86.7percent yield) which was used for the next step without any purification. ^l NMR (DMSO- tf, 400 MHz) δ ppm 6.01 (dd, J = 2.3, 7.9 Hz, 2H), 7.03 (d, J = 8.2 Hz, 1H); ESIMS found for C₆H₇BrN₂ mlz 186.8 (M+H).
86.7%	With hydrogenchloride; iron; ammonium chloride In ethanol; water at 65 - 80℃; for 3 h;	A suspension of 6-bromo-2-methyl-3-nitropyridine (XIV) (250 g, 1.15 mol, 1.00 eq) and NH₄C1 (300 g, 5.61 mol, 4.88 eq) in EtOH (3.50 L) and water (150 mL) was heated with stirring to 65°C. To this mixture was added Fe (130 g, 2.33 mol, 2.02 eq) and HQ (15.3 g, 419 mmol, 0.36 eq). The suspension was then heated to 80°C for another 3 h. The reaction was cooled to 25°C and filtered through a plug of Celite. The filtrate was concentrated under reduced pressure to yield a residue that was taken up in EtOAc (1 L x 3) and washed with brine. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to give 6- bromo-2-methylpyridin-3-amine (XV) as brown solid (373 g, 1.99 mol, 86.7percent yield) which was used for the next step without any purification. NMR (DMSO-de, 400 MHz) δ ppm 6.01 (dd, J = 2.3, 7.9 Hz, 2H), 7.03 (d, J= 8.2 Hz, IH); ESIMS found for C₆H₇BrN₂ mlz 186.8 (M+H).

86.7%	Stage #1: With ammonium chloride In ethanol; water at 65℃; Stage #2: With hydrogenchloride; iron In water at 80℃; for 3 h;	A suspension of 6-bromo-2-methyl-3-nitropyridine (XIV) (250 g, 1.15 mol, 1.00 eq) and NH₄C1 (300 g, 5.61 mol, 4.88 eq) in EtOH (3.50 L) and water (150 mL) was heated with stirring to 65°C. To this mixture was added Fe (130 g, 2.33 mol, 2.02 eq) and HQ (15.3 g, 419 mmol, 0.36 eq). The suspension was then heated to 80°C for another 3 h. The reaction was cooled to 25°C and filtered through a plug of Celite. The filtrate was concentrated under reduced pressure to yield a residue that was taken up in EtOAc (1 L x 3) and washed with brine. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to give 6-bromo-2-methylpyridin-3-amine (XV) as brown solid (373 g, 1.99 mol, 86.7percent yield) which was used for the next step without any purification. NMR (DMSO- e, 400 MHz) δ ppm 6.01 (dd, J = 2.3, 7.9 Hz, 2H), 7.03 (d, J = 8.2 Hz, 1H); ESIMS found for C₆H₇BrN₂ mlz 186.8 (M+H).
65%	With hydrogenchloride; iron In ethanol; water at 100℃; for 6 h;	To a stirred solution of 6-bromo-2-methyl-3-nitropyridine (15 g, 69.12 mmol) in ethanol (280 mL) was added iron powder (57.9 g, 1036 mmol) followed by conc HCl (30 mL). The reaction mixture was stirred for 6 h at 100° C., after completion of reaction (monitored by TLC), reaction mixture was cooled to room temperature, filtered through celite. Filterate was basified with saturated NaHCO₃ solution, extracted with EtOAc. Organic layer was washed with water followed by brine, dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure. The crude product was used in next step without further purification to afford desired compound (5.6 g, 65percent) as an off-white solid.

Reference： [1] Patent: WO2017/23993, 2017, A1, . Location in patent: Paragraph 0615; 0616
[2] Patent: WO2017/24004, 2017, A1, . Location in patent: Paragraph 0610-0611
[3] Patent: WO2017/24025, 2017, A1, . Location in patent: Paragraph 0611
[4] Patent: WO2017/24003, 2017, A1, . Location in patent: Paragraph 0610; 0611
[5] Patent: US2016/347717, 2016, A1, . Location in patent: Paragraph 0593; 0594

4
[ 22282-96-8 ]
[ 110-46-3 ]
[ 1227628-78-5 ]

Yield	Reaction Conditions	Operation in experiment
5 g	Stage #1: With potassium acetate; acetic anhydride In chloroform at 10 - 65℃; for 2 h; Stage #2: With 18-crown-6 ether In chloroform at 65℃; for 16 h; Stage #3: With potassium carbonate; potassium hydroxide In methanol; chloroform; water at 23℃; for 3 h;	To a stirred solution of 6-bromo-2-methyl-3-nitropyridine (5 g, 26.73 mmol) in chloroform was added potassium acetate (3.14 g, 32.08 mmol) and acetic anhydride (10.9 g, 106 mmol) at 10° C., the contents were stirred at 65° C. temperature for 2 h. After completion of reaction (monitored by TLC), the reaction mixture was cooled to room temperature, isoamylnitrite (3.75 g, 32.06 mmol) was added drop wise over a period of 15 min, followed by 18-crown-6 (0.7 g, 2.67 mmol) was added, reaction mixture was stirred at 65° C. for 16 h. After completion of reaction (monitored by TLC), the reaction mixture was cooled to room temperature, methanol and water mixture 120 mL (1:1) was added to the reaction mixture followed by potassium carbonate (34.48 g, 24.99 mmol) and KOH (4.2 g, 74.97 mmol), reaction mixture was stirred for 3 h at room temperature. After completion of reaction, reaction mixture was added diluted with ethyl acetate and the organic layer was washed with water followed by brine. The organic layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to obtain this title compound (5 g) as an off-white solid.

Reference： [1] Patent: US2016/347717, 2016, A1, . Location in patent: Paragraph 0595; 0596

5
[ 22282-96-8 ]
[ 1227628-78-5 ]

Reference： [1] Patent: WO2017/23993, 2017, A1,
[2] Patent: WO2017/24004, 2017, A1,
[3] Patent: WO2017/24025, 2017, A1,
[4] Patent: WO2017/24003, 2017, A1,

[ 22282-96-8 ] Synthesis Path-Downstream 1~88

1
[ 22282-96-8 ]
[ 66799-59-5 ]

Yield	Reaction Conditions	Operation in experiment
87%	With sodium methansulfinate; In dimethyl sulfoxide; at 20℃; for 1.5h;	Example 3.3: Preparation of 2-Methyl-6-(methylsulfonyl)pyridin-3-amine (Method 2); Step 1: Preparation of 2-Methyl-6-(methylsulfonyl)-3-nitropyridine; A mixture of <strong>[22282-96-8]6-bromo-2-methyl-3-nitropyridine</strong> (100 g, 461 mmol) and sodium methanesulfinate (47.0 g, 461 mmol) in DMSO (300 mL) was stirred at room temperature for 1.5 h. The reaction mixture was poured into ice-water (1 L) and stirred until all the ice had melted. The ice-cold solution was filtered, and a dark purple solid was collected. The solid collected was <n="30"/>dissolved in ethyl acetate (1 L). The solution was treated with activated charcoal, filtered through Celite. The Celite cake was washed with ethyl acetate, and the filtrate was collected. The solvent was evaporated from the filtrate under reduced pressure to give the title compound (87.0 g, 87%) as a yellow solid. Exact mass calculated for C7H8N2O4S: 216.0, Found: LCMS m/z = 217.2 (M+H+).

Reference： [1]Patent: WO2008/5576,2008,A1 .Location in patent: Page/Page column 28-29

2
[ 22282-96-8 ]
[ 267876-26-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 795 - 798

3
[ 288-88-0 ]
[ 22282-96-8 ]
[ 1001067-60-2 ]

Yield	Reaction Conditions	Operation in experiment
72%	With potassium carbonate; In dimethyl sulfoxide; at 20℃; for 17h;	Step A: Preparation of 2-Methyl-3-nitro-6-(1H-1,2,4-triazol-1-yl)pyridine. A mixture of <strong>[22282-96-8]6-bromo-2-methyl-3-nitropyridine</strong> (5.0 g, 23 mmol), 1H-1,2,4-triazole (1.6 g, 23 mmol), and potassium carbonate (3.2 g, 23 mmol) in DMSO (10 mL) was stirred at room temperature for 17 h. The reaction mixture was poured into ice-water (1 L) and stirred until all the ice had melted. The ice-cold solution was filtered to give the title compound (3.4 g, 72%) as a dark purple solid. Exact mass calculated for C8H7N5O2: 205.1. Found: LCMS m/z=206.2 (M+H+).
	With potassium carbonate; In dimethyl sulfoxide; at 20℃; for 36h;	Step 1: 2-Methyl-3-nitro-6-[1,2,4]triazol-1-yl-pyridine; A mixture of <strong>[22282-96-8]2-bromo-6-methyl-5-nitropyridine</strong> (ECA International Corporation, Palatine, Ill., USA; 2 g, 9.2 mmol), 1,2,4-triazole (Aldrich Chemical Company, Inc., Milwaukee, Wis., USA 0.64 g, 9.2 mmol) and potassium carbonate (1.27 g, 9.2 mmol) in dimethylsulfoxide (4 mL) was stirred at room temperature for 1.5 days and then poured into a mixture of ice and water (400 mL). The resulting mixture was stirred until all of the ice melted to give a dark purple slurry. The solid was filtered off to give 2-methyl-3-nitro-6-[1,2,4]triazol-1-yl-pyridine (1.34 g, 71%) as a purple solid with a purity estimated at 93% by LC-MS. This was used directly in the next step without further purification.

Reference： [1]Patent: US2009/286816,2009,A1 .Location in patent: Page/Page column 14
[2]Patent: US2009/286812,2009,A1 .Location in patent: Page/Page column 20

4
[ 22282-96-8 ]
[ 95-92-1 ]
[ 1222175-24-7 ]

Yield	Reaction Conditions	Operation in experiment
14%		To a solution of potassium ethoxide (1.1 g, 12.7 mmol) in diethylether / ethanol (5:1, 100 ml) is added oxalic acid diethyl ester (1.7 ml, 12.7 mmol) in one portion, and the resulting solution is stirred at room temperature for 30 minutes. 6-Bromo-2- methyl-3-nitro-pyridine (2.5 g, 11.5 mmol) is added as a suspension in diethylether (30 ml) and the reaction is stirred for 16 hours at room temperature. The precipitate is filtered off and washed with cold diethylether. The precipitate is dissolved in glacial acetic acid and then the solvent is evaporated in vacuo to give the product as a brown solid 500 mg, 14% LC/MS ESI m/z (M+H)+ = 317.2.

Reference： [1]Patent: WO2010/45188,2010,A1 .Location in patent: Page/Page column 96; 97

5
[ 22282-96-8 ]
[ 1443732-79-3 ]

Reference： [1]Patent: US2013/158066,2013,A1

6
[ 22282-96-8 ]
[ 1443732-80-6 ]

Reference： [1]Patent: US2013/158066,2013,A1

7
[ 22282-96-8 ]
[ 1443732-64-6 ]

Reference： [1]Patent: US2013/158066,2013,A1

8
[ 22282-96-8 ]
[ 1443732-65-7 ]

Reference： [1]Patent: US2013/158066,2013,A1

9
[ 22282-96-8 ]
2-(2-chloro-6-fluorophenyl)-5-(6-chloro-4-methylpyridin-3-yl)-1H-pyrrolo[3,2b]pyridine [ No CAS ]

Reference： [1]Patent: US2013/158066,2013,A1

10
[ 22282-96-8 ]
[ 64-17-5 ]
[ 387-45-1 ]
[ 1443732-78-2 ]
1-(2-chloro-6-fluorophenyl)-2-(6-ethoxy-3-nitropyridin-2-yl)ethanol [ No CAS ]