[ CAS No. 156118-16-0 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}

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

2D 3D

Structure of 156118-16-0 * Storage: {[proInfo.prStorage]}

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	Inquiry	{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,1,item.pr_is_large_size_no_price) ]}	{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate,item.pr_is_large_size_no_price) ]}	{[ item.pr_usastock ]}		{[ item.pr_chinastock ]}	{[ item.pr_remark ]}	Login		Inquiry

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 [ 156118-16-0 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 156118-16-0 ]

SDS Specification

Alternatived Products of [ 156118-16-0 ]

Product Details of [ 156118-16-0 ]

CAS No. :	156118-16-0	MDL No. :	MFCD08277280
Formula :	C₆H₇BrN₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	MVDBPMJQCXZKRB-UHFFFAOYSA-N
M.W :	187.04	Pubchem ID :	19926094
Synonyms :		Chemical Name :	3-Amino-6-bromo-4-methylpyridine

Calculated chemistry of [ 156118-16-0 ] Expand+

Physicochemical Properties

Num. heavy atoms :	9
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.17
Num. rotatable bonds :	0
Num. H-bond acceptors :	1.0
Num. H-bond donors :	1.0
Molar Refractivity :	41.31
TPSA :	38.91 ?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) :	-6.33 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.61
Log Po/w (XLOGP3) :	1.56
Log Po/w (WLOGP) :	1.74
Log Po/w (MLOGP) :	0.92
Log Po/w (SILICOS-IT) :	1.78
Consensus Log Po/w :	1.52

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-2.48
Solubility :	0.625 mg/ml ; 0.00334 mol/l
Class :	Soluble
Log S (Ali) :	-1.99
Solubility :	1.93 mg/ml ; 0.0103 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.91
Solubility :	0.232 mg/ml ; 0.00124 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.84

Safety of [ 156118-16-0 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 156118-16-0 ]

* 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 [ 156118-16-0 ]

[ 156118-16-0 ] Synthesis Path-Downstream 1~12

1
[ 156118-16-0 ]
[ 929617-35-6 ]

Yield	Reaction Conditions	Operation in experiment
59%	With acetic acid; sodium nitrite; at 20℃;	To a solutionof 27(4.00 g, 21.4 mmol) in AcOH (300 ml) was added NaNO2 (1.48 g, 21.4mmol) and stirred overnight at roomtemperature. The reaction mixture was concentrated in vacuo. The residue was diluted with EtOAc and washed with saturatedNaHCO3 aqueous solution and brine. Theorganic layer was dried over anhydrous MgSO4 and reduced underpressure. The residue was purified bysilica gel column chromatography (0-50% EtOAc in hexanes) to afford 28 as a yellow solid (2.48 g, 59%yield).1H NMR (300 MHz, CDCl3): delta ppm7.86 - 7.90 (m, 1 H), 8.09 - 8.14 (m, 1 H), 8.83 - 8.88 (m, 1 H).MS ESI/APCI Dual m/z: 198 [M+H] .
		Step 2 [0611] To a suspension 6-bromo-4-methylpyridin-3 -amine (XV) (186 g, 994 mmol, 1.00 eq) and KOAc ( 1 15 g, 1.17 mol, 1.18 eq) in CHC13 (3.50 L) was added Ac20 (405 g, 3.97 mol, 3.99 eq) and the suspension was stirred at 25C for 1 h and then heated at 60-70C to reflux for an additional 2 h. After cooling the suspension to 25C, isopentyl nitrate (233 g, 1.99 mol, 2.00 eq) and 18-crown-6 (21 g, 79.5 mmol, 0.08 eq) was added and the suspension heated to reflux for 12 h. After cooling to 25C, the suspension was filtered and the filtrate was concentrated under reduced pressure to yield a residue that was treated with a suspension of potassium carbonate (450 g) in a solution of methanol and water (450 mL) at 0C for 3 h. The suspension was concentrated under reduced pressure to yield a residue that was extracted with EtOAc (1000 mL x 3) and washed with brine. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to give 5-bromo-lH-pyrazolo[3,4-c]pyridine (XVI) (200 g, crude) as yellow solid. The crude product was used for the next step without any purification. NMR (DMSO- tf, 400 MHz) delta ppm 7.96 (s, 1H), 8.15 (s, 1H), 8.86 (s, 1H); ESIMS found for C6H4BrN3 mlz 198.3 (M+H).
		Step 2 [0612] To a suspension 6-bromo-4-methylpyridin-3 -amine (XV) (186 g, 994 mmol, 1.00 eq) and KOAc (115 g, 1.17 mol, 1.18 eq) in CHC13 (3.50 L) was added Ac20 (405 g, 3.97 mol, 3.99 eq) and the suspension was stirred at 25C for 1 h and then heated at 60-70C to reflux for an additional 2 h. After cooling the suspension to 25C, isopentyl nitrate (233 g, 1.99 mol, 2.00 eq) and 18-crown-6 (21 g, 79.5 mmol, 0.08 eq) was added and the suspension heated to reflux for 12 h. After cooling to 25C, the suspension was filtered and the filtrate was concentrated under reduced pressure to yield a residue that was treated with a suspension of potassium carbonate (450 g) in a solution of methanol and water (450 mL) at 0C for 3 h. The suspension was concentrated under reduced pressure to yield a residue that was extracted with EtOAc (1000 mL x 3) and washed with brine. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to give 5-bromo-lH-pyrazolo[3,4-c]pyridine (XVI) (200 g, crude) as yellow solid. The crude product was used for the next step without any purification. NMR (DMSO- tf, 400 MHz) delta ppm 7.96 (s, 1H), 8.15 (s, 1H), 8.86 (s, 1H); ESIMS found for C6H4BrN3 mlz 198.3 (M+H).

To a suspension [156118-16-0]6-bromo-4-methylpyridin-3-amine (XV) (186 g, 994 mmol, 1.00 eq) and KOAc (115 g, 1.17 mol, 1.18 eq) in CHC13 (3.50 L) was added Ac20 (405 g, 3.97 mol, 3.99 eq) and the suspension was stirred at 25C for 1 h and then heated at 60-70C to reflux for an additional 2 h. After cooling the suspension to 25C, isopentyl nitrate (233 g, 1.99 mol, 2.00 eq) and 18-crown-6 (21 g, 79.5 mmol, 0.08 eq) was added and the suspension heated to reflux for 12 h. After cooling to 25C, the suspension was filtered and the filtrate was concentrated under reduced pressure to yield a residue that was treated with a suspension of potassium carbonate (450 g) in a solution of methanol and water (450 mL) at 0C for 3 h. The suspension was concentrated under reduced pressure to yield a residue that was extracted with EtOAc (1000 mL x 3) and washed with brine. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to give 5-bromo-1H-pyrazolo[3,4-cjpyndine (XVI) (200 g, cmde) as yellow solid. The cmde product was used for the next step without any purification. ?H NMR (DM5 O-d6, 400 MHz) ppm 7.96 (s, 1H), 8.15 (s, 1H), 8.86 (s, 1H); ESIMS found for C6H4BrN3 mlz 198.3

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 5258 - 5264
[2]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 3441 - 3446
[3]Bioorganic and Medicinal Chemistry,2007,vol. 15,p. 2441 - 2452
[4]Patent: WO2017/23984,2017,A1 .Location in patent: Paragraph 0611
[5]Patent: WO2017/23980,2017,A1 .Location in patent: Paragraph 0612
[6]Patent: WO2017/24026,2017,A1 .Location in patent: Paragraph 0614; 0616

2
[ 23056-47-5 ]
[ 156118-16-0 ]

Yield	Reaction Conditions	Operation in experiment
97.4%	With hydrogenchloride; iron; ammonium chloride; In ethanol; water; at 50 - 80℃; for 3h;	A suspension of 2-bromo-4-methyl-5-nitropyridine (XIV) (200 g, 921 mmol, 1.00 eq) and NH4C1 (240 g, 4.49 mol, 4.87 eq) in EtOH (3.50 L) and water (150 mL) was heated with stirring to 50C. To this mixture was added Fe (120 g, 2.15 mol, 2.33 eq) and HC1 (10.2 g, 279 mmol, 0.30 eq). The suspension was then heated to 80C for another 3 h. The reaction was cooled to 25C 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 Lx 3) and washed with brine. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to give 6- bromo-4-methylpyridin-3-amine (XV) as brown solid (167.9 g, 898 mmol, 97.4% yield) which was used for the next step without any purification. ?H NMR (CDC13, 400 MHz) ppm 2.15 (s, 3H), 3.44 (br s, 2H), 7.14 (s, 1H), 7.78 (s, 1H); ESIMS found for C6H7BrN2 mlz 186.8 (M+H).
97.4%	With hydrogenchloride; iron; ammonium chloride; In ethanol; water; at 50 - 80℃; for 3h;	A suspension of 2-bromo-4-methyl-5-nitropyridine (XIV) (200 g, 921 mmol, 1.00 eq) and NH4C1 (240 g, 4.49 mol, 4.87 eq) in EtOH (3.50 L) and water (150 mL) was heated with stirring to 50C. To this mixture was added Fe (120 g, 2.15 mol, 2.33 eq) and HC1 (10.2 g, 279 mmol, 0.30 eq). The suspension was then heated to 80C for another 3 h. The reaction was cooled to 25C 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 Lx 3) and washed with brine. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to give 6- bromo-4-methylpyridin-3-amine (XV) as brown solid (167.9 g, 898 mmol, 97.4% yield) which was used for the next step without any purification. ?H NMR (CDC13, 400 MHz) ppm 2.15 (s, 3H), 3.44 (br s, 2H), 7.14 (s, 1H), 7.78 (s, 1H); ESIMS found for C6H7BrN2 mlz 186.8 (M+H).
93%	With hydrogen; In tetrahydrofuran; water; at 20℃;	To a solutionof 2-bromo-4-methyl-5-nitropyridine (5.00 g, 23.0 mmol) in tetrahydrofuran (THF)(30 ml) was added Raney nickel (slurry in water). The reaction mixture washydrogenated (balloon) overnight at room temperature. The mixture was filteredthrough Celite, and concentrated under reduced pressure. The residue waspurified by silica gel column chromatography (0-50% EtOAc in hexanes) to afford27 as a yellow solid (4.02 g, 93%yield).1H NMR (300 MHz, CDCl3): delta ppm2.15 (d, J = 0.9 Hz, 3 H), 7.14 (s, 1 H), 7.78 (s, 1 H).

	With iron; ammonium chloride; In water; at 90℃; for 1.25h;	1.12. Synthesis of 6-bromo-4-methyl-pyridin-3-ylamine (Int.20) A mixture of NH4Cl (14.9 mmol) and iron powder (18.4 mmol) in H2O (5 mL) was stirred at 90 C. 2-bromo-4-methyl-5-nitropyridine (2.3 mmol) was added in portions. The mixture was stirred at 90 C. for 1 h and 15 min. The reaction was stopped and extracted with EtOAc. The organic layer was dried (Na2SO4) and concentrated to yield the desired product.
	With iron; ammonium chloride; In water; at 90℃; for 1.25h;	1.12. Synthesis of 6-bromo-4-methyl-pyridin-3-ylamine (mt. 20) 1002591 A mixture of NH4C1 (14.9 mmol) and iron powder (18.4 mmol) in H20 (5 mL) was stirred at90C. 2-bromo-4-methyl-5-nitropyridine (2.3 mmol) was added in portions. The mixture was stirred at90C for 1 h and 15 mm. The reaction was stopped and extracted with EtOAc. The organic layer wasdried (Na2SO4) and concentrated to yield the desired product.
	With iron; ammonium chloride; In water; at 90℃; for 1.25h;	A mixture of NH4C1 (14.9 mmol) and iron powder (18.4 mmol) in H20 (5 mE) was stirred at 90 C. 2-bromo-4- methyl-5-nitropyridine (2.3 mmol) was added in portions. The mixture was stirred at 90 C. for 1 h and 15 mm. The reaction was stopped and extracted with EtOAc. The organic layer was dried (Na2SO4) and concentrated to yield the desired product.
	With hydrogenchloride; iron; ammonium chloride; In ethanol; water; at 50 - 80℃; for 3h;	Step 1 [0610] A suspension of 2-bromo-4-methyl-5-nitropyridine (XIV) (200 g, 921 mmol, 1.00 eq) and NH4C1 (240 g, 4.49 mol, 4.87 eq) in EtOH (3.50 L) and water (150 mL) was heated with stirring to 50C. To this mixture was added Fe ( 120 g, 2.15 mol, 2.33 eq) and HC1 (10.2 g, 279 mmol, 0.30 eq). The suspension was then heated to 80C for another 3 h. The reaction was cooled to 25C 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-4-methylpyridin-3 -amine (XV) as brown solid (167.9 g, 898 mmol, 97.4% yield) which was used for the next step without any purification. l NMR (CDC , 400 MHz) delta ppm 2.15 (s, 3H), 3.44 (br s, 2H), 7.14 (s, 1H), 7.78 (s, 1H); ESIMS found for C6H7BrN2 mlz 186.8 (M+H).
	With hydrogenchloride; iron; ammonium chloride; In ethanol; water; at 50 - 80℃; for 3h;	Step 1 [0611] A suspension of 2-bromo-4-methyl-5-nitropyridine (XIV) (200 g, 921 mmol, 1.00 eq) and NH4C1 (240 g, 4.49 mol, 4.87 eq) in EtOH (3.50 L) and water (150 mL) was heated with stirring to 50C. To this mixture was added Fe (120 g, 2.15 mol, 2.33 eq) and HC1 (10.2 g, 279 mmol, 0.30 eq). The suspension was then heated to 80C for another 3 h. The reaction was cooled to 25C 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-4-methylpyridin-3 -amine (XV) as brown solid (167.9 g, 898 mmol, 97.4% yield) which was used for the next step without any purification. l NMR (CDC , 400 MHz) delta ppm 2.15 (s, 3H), 3.44 (br s, 2H), 7.14 (s, 1H), 7.78 (s, 1H); ESIMS found for C6H7BrN2 mlz 186.8 (M+H).

Reference： [1]Patent: WO2017/23975,2017,A1 .Location in patent: Paragraph 0610; 0611
[2]Patent: WO2017/24026,2017,A1 .Location in patent: Paragraph 0614; 0615
[3]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 3441 - 3446
[4]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 5258 - 5264
[5]Bioorganic and Medicinal Chemistry,2007,vol. 15,p. 2441 - 2452
[6]Patent: US2015/203455,2015,A1 .Location in patent: Paragraph 0455-0456
[7]Patent: WO2015/110378,2015,A1 .Location in patent: Paragraph 00259; 00312
[8]Patent: US9440929,2016,B2 .Location in patent: Page/Page column 58; 59
[9]Patent: WO2017/23984,2017,A1 .Location in patent: Paragraph 0610
[10]Patent: WO2017/23980,2017,A1 .Location in patent: Paragraph 0611

3
[ 156118-16-0 ]
[ 929617-31-2 ]