[ CAS No. 89488-30-2 ] {[proInfo.proName]}

Name: 89488-30-2|5-Bromo-3-methylpyridin-2(1H)-one|98%
Brand: Ambeed
SKU: A172876
Price: 8.0 USD
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Quality Control of [ 89488-30-2 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 89488-30-2 ]

SDS Specification

Alternatived Products of [ 89488-30-2 ]

Product Details of [ 89488-30-2 ]

CAS No. :	89488-30-2	MDL No. :	MFCD03427657
Formula :	C₆H₆BrNO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	HXPMRPRBABWPKL-UHFFFAOYSA-N
M.W :	188.02	Pubchem ID :	285436
Synonyms :

Calculated chemistry of [ 89488-30-2 ]

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 :	39.73
TPSA :	32.86 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.74 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.66
Log Po/w (XLOGP3) :	0.99
Log Po/w (WLOGP) :	1.45
Log Po/w (MLOGP) :	1.38
Log Po/w (SILICOS-IT) :	2.64
Consensus Log Po/w :	1.62

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.12
Solubility :	1.42 mg/ml ; 0.00754 mol/l
Class :	Soluble
Log S (Ali) :	-1.27
Solubility :	10.1 mg/ml ; 0.0539 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-3.17
Solubility :	0.126 mg/ml ; 0.000671 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.63

Safety of [ 89488-30-2 ]

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 [ 89488-30-2 ]

* 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 [ 89488-30-2 ]
Downstream synthetic route of [ 89488-30-2 ]

[ 89488-30-2 ] Synthesis Path-Upstream 1~6

1
[ 3430-21-5 ]
[ 89488-30-2 ]

Yield	Reaction Conditions	Operation in experiment
84%	With sodium nitrite In dichloromethane; sulfuric acid; water	EXAMPLE 11A 5-bromo-2-hydroxy-3-methylpyridine 2-Amino-5-bromo-3-methylpyridine (5.0 g, 26.7 mmol) in 2.6M H₂SO₄ (70 mL) was treated with sodium nitrite (5.0 g, 72.5 mmol) in water (10 mL) dropwise at 0° C. The mixture was allowed to warm to ambient temperature and stir for 1.5 hours. The mixture was filtered and the filtercake washed with cold water. The filtercake was dissolved in dichloromethane (100 mL), dried (MgSO₄), and concentrated to provide the title compound (4.2 g, 84percent yield). MS (DCI/NH₃) M/z 188/190 (M+H)⁺.
84%	With sulfuric acid; sodium nitrite In water at 0 - 20℃; for 1.5 h;	Sodium nitrite (5.0 g, 72.5 mmol) in water (10 mL) was added dropwise to a cooled (0 °C) mixture of 2-amino-5-bromo-3-methylpyridine (5.0 g, 26.7 mmol; Lancaster) in 2.6 M sulfuric acid (70 mL). The mixture was allowed to warm to ambient temperature, stir for 1.5 hours, filtered, and the filtercake was washed with cold water and air dried. The precipitate was dissolved in dichloromethane (100 mL), dried (MgSO4), and concentrated to provide the title compound as a solid (4.2 g, 84percent). MS (DCI/NH3) m/z 348 (M+H)+.

Reference： [1] Patent: US2002/19388, 2002, A1,
[2] Patent: EP1428824, 2004, A1, . Location in patent: Page 49
[3] Patent: WO2008/67644, 2008, A1, . Location in patent: Page/Page column 39

2
[ 89488-30-2 ]
[ 29241-60-9 ]

Yield	Reaction Conditions	Operation in experiment
78%	With trichlorophosphate In dichloromethane; N,N-dimethyl-formamide	EXAMPLE 11B 5-bromo-2-chloro-3-methylpyridine The product from Example 11A (4.1 g, 221.8 mmol) in DMF (40 mL) was treated with phosphorus oxychloride (10 g, 65.4 mmol) dropwise at 0° C. After heating at 120° C. for 2 hours, the mixture was cooled and poured onto ice/water. The mixture was made basic with NH₄OH, filtered, and the filtercake washed with ice water. The obtained solid was dissolved in dichloromethane (100 mL), washed with brine, and dried (MgSO₄). The dried solution was filtered through a pad of silica using dichloromethane and the filtrate concentrated to provide the title compound as a white solid (3.48 g, 78percent yield): ¹H NMR (CDCl₃, 300 MHz) δ 2.39 (s, 3H), 7.70 (m, 1H), 8.31, d, J=3 Hz, 1H).
78%	With trichlorophosphate In DMF (N,N-dimethyl-formamide) at 0 - 120℃; for 2 h;	The product from Example 49A (4.1 g, 221.8 mmol) in DMF (40 mL) was treated with phosphorous oxychloride (10 g, 65.4 mmol) dropwise at 0 °C. The resulting solution was heated at 120 °C for 2 hours, cooled and poured onto ice/H2O. The mixture was made basic with NH4OH. The precipitate was filtered, washed with ice water, dissolved in dichloromethane (100 mL), washed with brine, and dried (MgSO4). The solution was filtered through a pad of silica (dichloromethane) and concentrated to leave the title compound as a white solid (3.48 g, 78percent). MS (DCI/NH3) m/z 348 (M+H)+.

Reference： [1] Patent: US2002/19388, 2002, A1,
[2] Patent: EP1428824, 2004, A1, . Location in patent: Page 49

3
[ 89488-30-2 ]
[ 74-88-4 ]
[ 760207-87-2 ]

Reference： [1] Patent: WO2008/67644, 2008, A1, . Location in patent: Page/Page column 39-40

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[ 89488-30-2 ]
[ 74-88-4 ]
[ 760207-87-2 ]

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 24, p. 7512 - 7517

5
[ 124-38-9 ]
[ 89488-30-2 ]
[ 66909-27-1 ]

Reference： [1] Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 16, p. 6106 - 6122

6
[ 89488-30-2 ]
[ 1425045-01-7 ]

Reference： [1] Patent: US2018/44335, 2018, A1,

[ 89488-30-2 ] Synthesis Path-Downstream 1~88

1
[ 3430-21-5 ]
[ 89488-30-2 ]

Yield	Reaction Conditions	Operation in experiment
84%	With sodium nitrite; In dichloromethane; sulfuric acid; water;	EXAMPLE 11A 5-bromo-2-hydroxy-3-methylpyridine 2-Amino-5-bromo-3-methylpyridine (5.0 g, 26.7 mmol) in 2.6M H2SO4 (70 mL) was treated with sodium nitrite (5.0 g, 72.5 mmol) in water (10 mL) dropwise at 0 C. The mixture was allowed to warm to ambient temperature and stir for 1.5 hours. The mixture was filtered and the filtercake washed with cold water. The filtercake was dissolved in dichloromethane (100 mL), dried (MgSO4), and concentrated to provide the title compound (4.2 g, 84% yield). MS (DCI/NH3) M/z 188/190 (M+H)+.
84%	With sulfuric acid; sodium nitrite; In water; at 0 - 20℃; for 1.5h;	Sodium nitrite (5.0 g, 72.5 mmol) in water (10 mL) was added dropwise to a cooled (0 C) mixture of 2-amino-5-bromo-3-methylpyridine (5.0 g, 26.7 mmol; Lancaster) in 2.6 M sulfuric acid (70 mL). The mixture was allowed to warm to ambient temperature, stir for 1.5 hours, filtered, and the filtercake was washed with cold water and air dried. The precipitate was dissolved in dichloromethane (100 mL), dried (MgSO4), and concentrated to provide the title compound as a solid (4.2 g, 84%). MS (DCI/NH3) m/z 348 (M+H)+.
	With sulfuric acid; water; sodium nitrite; at 0 - 20℃; for 0.5h;	To a mixture of compound 4b1 (600 mg, 3.2 mmol) and concentrated H2SO4 (1.6 mL) and water (18.4 mL) is added drop wise a solution of NaNO2 (243.5 mg, 3.53 mmol) in water (1.6 mL) at 00C. After 30 min at room temperature the reaction is filtered and the resulting solid is washed with water and dried under high vacuum to give compound 4b2.

Reference： [1]Patent: US2002/19388,2002,A1
[2]Patent: EP1428824,2004,A1 .Location in patent: Page 49
[3]Patent: WO2008/67644,2008,A1 .Location in patent: Page/Page column 39

2
[ 89488-30-2 ]
[ 29241-60-9 ]

Yield	Reaction Conditions	Operation in experiment
78%	With trichlorophosphate; In dichloromethane; N,N-dimethyl-formamide;	EXAMPLE 11B 5-bromo-2-chloro-3-methylpyridine The product from Example 11A (4.1 g, 221.8 mmol) in DMF (40 mL) was treated with phosphorus oxychloride (10 g, 65.4 mmol) dropwise at 0 C. After heating at 120 C. for 2 hours, the mixture was cooled and poured onto ice/water. The mixture was made basic with NH4OH, filtered, and the filtercake washed with ice water. The obtained solid was dissolved in dichloromethane (100 mL), washed with brine, and dried (MgSO4). The dried solution was filtered through a pad of silica using dichloromethane and the filtrate concentrated to provide the title compound as a white solid (3.48 g, 78% yield): 1H NMR (CDCl3, 300 MHz) delta 2.39 (s, 3H), 7.70 (m, 1H), 8.31, d, J=3 Hz, 1H).
78%	With trichlorophosphate; In DMF (N,N-dimethyl-formamide); at 0 - 120℃; for 2.0h;	The product from Example 49A (4.1 g, 221.8 mmol) in DMF (40 mL) was treated with phosphorous oxychloride (10 g, 65.4 mmol) dropwise at 0 C. The resulting solution was heated at 120 C for 2 hours, cooled and poured onto ice/H2O. The mixture was made basic with NH4OH. The precipitate was filtered, washed with ice water, dissolved in dichloromethane (100 mL), washed with brine, and dried (MgSO4). The solution was filtered through a pad of silica (dichloromethane) and concentrated to leave the title compound as a white solid (3.48 g, 78%). MS (DCI/NH3) m/z 348 (M+H)+.

Reference： [1]Patent: US2002/19388,2002,A1
[2]Patent: EP1428824,2004,A1 .Location in patent: Page 49

3
[ 89488-30-2 ]
[ 74-88-4 ]
[ 760207-87-2 ]

Yield	Reaction Conditions	Operation in experiment
	With silver carbonate; In dichloromethane; at 20℃;	To a mixture of compound 4b2 (2 g, 10.6 mmol) and CH2CI2 (100 mL) is added Ag2CO3 (8.8 g, 31.9 mmol) and CH3I (7 mL, 112 mmol). The reaction mixture is stirred at room temperature overnight, then filtered through diatomaceous earth <n="41"/>(Celite). The filtrate is concentrated under reduced pressure to give compound4b3.

Reference： [1]Patent: WO2008/67644,2008,A1 .Location in patent: Page/Page column 39-40

4
[ 124-38-9 ]
[ 89488-30-2 ]
[ 66909-27-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 6106 - 6122

5
[ 89488-30-2 ]
[ 18162-48-6 ]
[ 1383847-26-4 ]

Yield	Reaction Conditions	Operation in experiment
100%	With triethylamine; In dichloromethane; at 20 - 25℃; for 4.0h;	Example 14i 5-Bromo-2-(tert-butyldimethylsilyloxy)-3-methylpyridine Triethylamine (29.4 mL, 211 mmol) was added to a suspension of <strong>[89488-30-2]5-bromo-2-hydroxy-3-methylpyridine</strong> (15.9 g, 84.6 mmol) and tert-butyldimethylchlorosilane (15.29 g, 101 mmol) in CH2Cl2 (280 mL). After 4 h at r.t. water was added and the phases were separated. The organic phase was washed once with water, dried (Na2SO4), filtered, concentrated and co-evaporated twice with toluene to give the title compound (25.8 g, quant. yield): 1H NMR (400 MHz, DMSO-d6) delta ppm 0.26-0.29 (m, 6H), 0.96 (s, 9H), 2.12 (s, 3H), 7.80 (dd, 1H), 8.03 (d, 1H); MS (ES+) m/z 302, 304 [M+H]+.

Reference： [1]Patent: US2012/165346,2012,A1 .Location in patent: Page/Page column 15-16

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[ 1383847-10-6 ]

Reference： [1]Patent: US2012/165346,2012,A1

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[ 1383847-12-8 ]

Reference： [1]Patent: US2012/165346,2012,A1

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[ 1383846-85-2 ]

Reference： [1]Patent: US2012/165346,2012,A1

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[ 1383846-86-3 ]

Reference： [1]Patent: US2012/165346,2012,A1

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[ 1383846-97-6 ]

Reference： [1]Patent: US2012/165346,2012,A1

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[ 1383846-98-7 ]

Reference： [1]Patent: US2012/165346,2012,A1

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[ 1383846-99-8 ]

Reference： [1]Patent: US2012/165346,2012,A1

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[ 1383847-00-4 ]

Reference： [1]Patent: US2012/165346,2012,A1

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[ 1383847-16-2 ]

Reference： [1]Patent: US2012/165346,2012,A1

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[ 1383847-25-3 ]

Reference： [1]Patent: US2012/165346,2012,A1

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Reference： [1]Patent: US2012/165346,2012,A1

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Reference： [1]Patent: US2012/165346,2012,A1

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Reference： [1]Patent: US2012/165346,2012,A1

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[ 1383847-31-1 ]

Reference： [1]Patent: US2012/165346,2012,A1

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[ 1400978-02-0 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 9346 - 9361,16

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[ 1400978-00-8 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 9346 - 9361,16

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[ 1400978-01-9 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 9346 - 9361,16

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[ 1400977-89-0 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 9346 - 9361,16

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[ 1383847-15-1 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 9346 - 9361,16

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[ 1400977-90-3 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 9346 - 9361,16

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[ 1400977-91-4 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 9346 - 9361,16

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[ 1383846-83-0 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 9346 - 9361,16

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[ 89488-30-2 ]
[ 75-03-6 ]
[ 916344-85-9 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 9346 - 9361,16

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[ 89488-30-2 ]
1,5-dimethyl-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid [2-benzylamino-4-(4-methyl-piperazin-1-yl)-phenyl]-amide [ No CAS ]

Reference： [1]Patent: WO2015/22332,2015,A1
[2]Patent: US2015/51208,2015,A1

30
[ 89488-30-2 ]
{3-benzylamino-4-[(1,5-dimethyl-6-oxo-1,6-dihydro-pyridine-3-carbonyl)-amino]-phenyl}-carbamic acid tert-butyl ester [ No CAS ]

Reference： [1]Patent: WO2015/22332,2015,A1
[2]Patent: US2015/51208,2015,A1

31
[ 89488-30-2 ]
1,5-dimethyl-6-oxo-1,6-dihydro-pyridine-3-carbonyl chloride [ No CAS ]

Reference： [1]Patent: WO2015/22332,2015,A1
[2]Patent: US2015/51208,2015,A1

32
[ 89488-30-2 ]
5-(1-benzyl-6-morpholin-4-yl-1H-imidazo[4,5-c]pyridin-2-yl)-1,3-dimethyl-1H-pyridin-2-one [ No CAS ]

Reference： [1]Patent: WO2015/22332,2015,A1
[2]Patent: US2015/51208,2015,A1

33
[ 89488-30-2 ]
1,5-dimethyl-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid (4-benzylamino-6-morpholin-4-yl-pyridin-3-yl)-amide [ No CAS ]

Reference： [1]Patent: WO2015/22332,2015,A1
[2]Patent: US2015/51208,2015,A1

34
[ 89488-30-2 ]
{4-benzylamino-5-[(1,5-dimethyl-6-oxo-1,6-dihydro-pyridine-3-carbonyl)-amino]-pyridin-2-yl}-carbamic acid tert-butyl ester [ No CAS ]

Reference： [1]Patent: WO2015/22332,2015,A1
[2]Patent: US2015/51208,2015,A1

35
[ 89488-30-2 ]
N-[1-benzyl-2-(1,5-dimethyl-6-oxo-1,6-dihydro-pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-6-yl]-acetamide [ No CAS ]

Reference： [1]Patent: WO2015/22332,2015,A1
[2]Patent: US2015/51208,2015,A1

36
[ 89488-30-2 ]
5-(6-amino-1-benzyl-1H-imidazo[4,5-c]pyridin-2-yl)-1,3-dimethyl-1H-pyridin-2-one [ No CAS ]

Reference： [1]Patent: WO2015/22332,2015,A1
[2]Patent: US2015/51208,2015,A1

37
[ 89488-30-2 ]
1,5-dimethyl-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid [ No CAS ]

Reference： [1]Patent: WO2015/22332,2015,A1
[2]Patent: US2015/51208,2015,A1
[3]Patent: WO2015/169962,2015,A1
[4]Patent: WO2019/145410,2019,A1

38
[ 89488-30-2 ]
[ 74-88-4 ]
[ 51417-13-1 ]

Yield	Reaction Conditions	Operation in experiment
98%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 16.0h;	5-Bromo-1,3-dimethyl-1H-pyridin-2-one B-1 To a suspension of <strong>[89488-30-2]5-bromo-2-hydroxy-3-methyl pyridine</strong> A1 (1.000 g; 5.053 mmol) and potassium carbonate (1.397 g; 10.105 mmol) in DMF (5.000 ml) is carefully added iodomethane (0.346 ml; 5.558 mmol). The reaction mixture is stirred overnight (16 h) at room temperature. The reaction mixture is then quenched with 10% ammonia solution (10 ml) and 30 ml water is added. It is extracted with 3*50 ml EtOAc. The combined organic layer is dried with Na2SO4, filtered and concentrated under reduced pressure to afford the product. Yield: 98% (1.0 g; 4.95 mmol) HPLC-MS: (M+H)+=202/204; tRet=0.65 min; method LCMS BAS1
98%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 16.0h;	5-Bromo- 1 ,3-dimethyl- 1H-pyridin-2-one B-i To a suspension of <strong>[89488-30-2]5-bromo-2-hydroxy-3-methyl pyridine</strong> Al (1.000 g; 5.053mmo 1) and potassium carbonate (1.397 g; 10.105 mmo 1) in DMF (5.000 ml) iscarefully added iodomethane (0.346 ml; 5.558 mmol). The reaction mixture is stirred overnight (1 6h) at room temperature. The reaction mixture is then quenched with 10% ammonia solution (10 ml) and 30 ml water is added. It is extracted with 3x50 ml EtOAc. The combined organic layer is dried with Na2SO4, filtered andconcentrated under reduced pressure to afford the product.Yield: 98% (1.0 g; 4.95 mmol)HPLC-MS: (M+H) = 202/204; tRet = 0.65 mm; method LCMS BAS1
98%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 16.0h;	5-Bromo- 1 ,3-dimethyl- lH-pyridin-2- ne B- 1 To a suspension of <strong>[89488-30-2]5-bromo-2-hydroxy-3-methyl pyridine</strong> Al (1.000 g; 5.053 mmol) and potassium carbonate (1.397 g; 10.105 mmol) in DMF (5.000 ml) is carefully added iodomethane (0.346 ml; 5.558 mmol). The reaction mixture is stirred overnight (16h) at room temperature. The reaction mixture is then quenched with 10% ammonia solution (10 ml) and 30 ml water is added. It is extracted with 3x50 ml EtOAc. The combined organic layer is dried with Na2S04, filtered and concentrated under reduced pressure to afford the product. Yield: 98% (1.0 g; 4.95 mmol) HPLC-MS: (M+H)+ = 202/204; tRet = 0.65 min; method LCMS BAS1

98%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;Inert atmosphere;	To a suspension of starting material A (1.00 g; 5.053 mmol) and potassium carbonate (1.397 g; 10.105 mmol) in DMF (5 ml_) is carefully added iodomethane (0.346 ml5.558 mmol). The reaction mixture is stirred overnight (16 h) at room temperature. The reaction mixture is then quenched with 10 % ammonia solution (10 ml_) and 30 ml_ water is added. It is extracted with 3 x 50 mL EtOAc. The combined organic layer is dried with Na2S04, filtered and concentrated under reduced pressure to afford the product. Yield: 98 % (1.0 g; 4.95 mmol) ( HPLC-MS: (M+H)+ = 202/204; tRet = 0.65 min; method LCMS BAS1
	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 16.0h;	5-Bromo-1,3-dimethyl-1H-pyridin-2-one C-1 To a suspension of <strong>[89488-30-2]5-bromo-2-hydroxy-3-methyl pyridine</strong> B1 (1.000 g; 5.053 mmol) and potassium carbonate (1.397 g; 10.105 mmol) in DMF (5.0 mL) is carefully added iodomethane (0.346 mL; 5.558 mmol). The reaction mixture is stirred at RT overnight (16 h). The reaction mixture is then quenched with 10% ammonia solution (10.0 mL) and water (30.0 mL) is added. The mixture is extracted with EtOAc (3*50.0 mL). The combined organic layer is dried with Na2SO4, filtered and concentrated under reduced pressure to afford the product. HPLC-MS: (M+H)+=202/204; tRet=0.65 min; method M1

Reference： [1]Patent: US2015/51208,2015,A1 .Location in patent: Paragraph 0179; 0180; 0181; 0182
[2]Patent: WO2015/22332,2015,A1 .Location in patent: Page/Page column 45
[3]Patent: WO2015/169962,2015,A1 .Location in patent: Page/Page column 36
[4]Patent: WO2019/145410,2019,A1 .Location in patent: Page/Page column 20; 24
[5]Patent: US2018/44335,2018,A1 .Location in patent: Paragraph 0417

39
[ 89488-30-2 ]
5-[1-benzyl-6-(4-methylpiperazin-1-yl)-1H-1,3-benzodiazol-2-yl]-1,3-dimethyl-1,2-dihydropyridin-2-one [ No CAS ]

Reference： [1]Patent: WO2015/22332,2015,A1
[2]Patent: US2015/51208,2015,A1

40
[ 89488-30-2 ]
5-(6-amino-1-benzyl-1H-benzoimidazol-2-yl)-1,3-dimethyl-1H-pyridin-2-one [ No CAS ]

Reference： [1]Patent: WO2015/22332,2015,A1
[2]Patent: US2015/51208,2015,A1

41
[ 89488-30-2 ]
N-[3-benzyl-2-(1,5-dimethyl-6-oxo-1,6-dihydro-pyridin-3-yl)-3H-benzoimidazol-5-yl]-acetamide [ No CAS ]

Reference： [1]Patent: WO2015/22332,2015,A1
[2]Patent: US2015/51208,2015,A1

42
[ 89488-30-2 ]
5-(1-benzyl-6-fluoro-1H-benzoimidazol-2-yl)-1,3-dimethyl-1H-pyridin-2-one [ No CAS ]

Reference： [1]Patent: WO2015/22332,2015,A1
[2]Patent: US2015/51208,2015,A1

43
[ 89488-30-2 ]
racemic 1,5-dimethyl-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid [6-chloro-4-(1-pyridin-2-yl-ethylamino)-pyridin-3-yl]-amide [ No CAS ]

Reference： [1]Patent: WO2015/22332,2015,A1
[2]Patent: US2015/51208,2015,A1

44
[ 89488-30-2 ]
racemic 5-[6-chloro-1-(1-pyridin-2-yl-ethyl)-1H-imidazo[4,5-c]pyridin-2-yl]-1,3-dimethyl-1H-pyridin-2-one [ No CAS ]

Reference： [1]Patent: WO2015/22332,2015,A1
[2]Patent: US2015/51208,2015,A1

45
[ 89488-30-2 ]
racemic 5-[6-cyclopropylmethoxy-1-(1-pyridin-2-yl-ethyl)-1H-imidazo[4,5-c]pyridin-2-yl]-1,3-dimethyl-1H-pyridin-2-one [ No CAS ]

Reference： [1]Patent: WO2015/22332,2015,A1
[2]Patent: US2015/51208,2015,A1

46
[ 89488-30-2 ]
1,5-dimethyl-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid methyl ester [ No CAS ]

Reference： [1]Patent: WO2015/22332,2015,A1
[2]Patent: WO2015/169962,2015,A1
[3]Patent: WO2019/145410,2019,A1

47
[ 89488-30-2 ]
C₂₁H₂₀FN₃O₂ [ No CAS ]

Reference： [1]Patent: WO2015/22332,2015,A1
[2]Patent: US2015/51208,2015,A1

48
[ 89488-30-2 ]
N-[3-[1-(cyclopropylmethyl)-5-methyl-6-oxopyridin-3-yl]-4-(2,4-difluorophenoxy)phenyl]ethanesulfonamide [ No CAS ]

Reference： [1]Patent: US2015/111885,2015,A1

49
[ 89488-30-2 ]
[ 7051-34-5 ]
5-bromo-1-(cyclopropylmethyl)-3-methylpyridin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	With potassium carbonate; In N,N-dimethyl-formamide; at 70℃; for 3.0h;	Potassium carbonate (1.32 g, 9.57 mmol) was added to 5-bromo-3-methyl-2-hydroxypyridine (600 mg, 3.19 mmol) and bromomethylcyclopropane (861 mg, 6.38 mmol) in DMF (6 mL). After heating at 70 C. for 3 h, EA extractive work up and silica gel chromatography (PE:EA=30:1?10:1), the title compound (510 mg, yield: 66.0%) was obtained as a white solid. 1H NMR: (CDCl3, 400 MHz) delta: 7.39 (d, J=2.0 Hz, 1H), 7.26 (d, J=2.0 Hz, 1H), 3.77 (d, J=6.8 Hz, 2H), 2.15 (s, 3H), 0.65-0.60 (m, 2H), 0.40-0.37 (m, 2H). LCMS: 242.1; 244.1 (M+H)+

Reference： [1]Patent: US2015/111885,2015,A1 .Location in patent: Paragraph 1040; 1041

50
[ 89488-30-2 ]
1-[2-(difluoromethoxy)benzyl]-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzimidazole [ No CAS ]
5-{1-[2-(difluoromethoxy)benzyl]-2-methyl-1H-benzimidazol-6-yl}-3-methylpyridin-2(1H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
2%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 105℃;	Example 509 5-{1-[2-(Difluoromethoxy)benzyl]-2-methyl-1H-benzimidazol-6-yl}-3-methylpyridin-2(1H)-one To Intermediate 57 (140 mg, 0.34 mmol) were added <strong>[89488-30-2]5-bromo-3-methylpyridin-2-ol</strong> (76 mg, 0.41 mmol), Pd(PPh3)4 (20 mg, 0.016 mmol), 2M aqueous Na2CO3 solution (2 mL) and 1,4-dioxane (10 mL). The reaction mixture was stirred at 105 C. for 4 h. Further Pd(PPh3)4 (20 mg, 0.016 mmol) and Na2CO3 solution (1 mL) were added and the reaction mixture was stirred at 105 C. overnight. The reaction mixture was cooled to ambient temperature, diluted with water (1 mL) and extracted with ethyl acetate (2*20 mL). The combined organic layers were concentrated in vacuo and the crude residue was purified by silica flash column chromatography (0-10% MeOH/DCM) and then by preparative HPLC to yield, after freeze-drying, the title compound (3 mg, 2%) as a white solid. deltaH (d6-DMSO) 11.59-11.25 (1H, br s), 7.72 (1H, d, J 1.4 Hz), 7.63-7.49 (3H, m), 7.40-7.33 (3H, m), 7.26 (1H, d, J 7.6 Hz), 7.16-7.11 (1H, m), 6.68-6.65 (1H, m), 5.52 (2H, s), 2.45 (3H, s), 2.00 (3H, s). LCMS (pH 3) 396.8, MH+, RT 1.33 minutes, 100% UV. LCMS (pH 10) 396.8, MH+, RT 1.66 minutes, 100% UV.

Reference： [1]Patent: US2015/152065,2015,A1 .Location in patent: Paragraph 0771

51
[ 89488-30-2 ]
N-[4-[1-(cyclopropylmethyl)-5-methyl-6-oxopyridin-3-yl]-5-(2,4-difluorophenoxy)pyrimidin-2-yl]methanesulfonamide [ No CAS ]

Reference： [1]Patent: US2015/111885,2015,A1

52
[ 89488-30-2 ]
1-(cyclopropylmethyl)-3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-one [ No CAS ]

Reference： [1]Patent: US2015/111885,2015,A1

53
[ 89488-30-2 ]
1-(cyclopropylmethyl)-5-[5-(2,4-difluorophenoxy)-2-methylsulfonylpyrimidin-4-yl]-3-methylpyridin-2-one [ No CAS ]

Reference： [1]Patent: US2015/111885,2015,A1

54
[ 89488-30-2 ]
2-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-3-((S)-2-methoxy-1-methylethyl)-5,7,7-trimethyl-5,7-dihydro-3H-imidazo[4,5-f]indol-6-one [ No CAS ]

Reference： [1]Patent: WO2015/169962,2015,A1

55
[ 89488-30-2 ]
1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid [6-((S)-2-methoxy-1-methylethylamino)-1,3,3-trimethyl-2-oxo-2,3-dihydro-1H-indol-5-yl]amide [ No CAS ]

Reference： [1]Patent: WO2015/169962,2015,A1

56
[ 89488-30-2 ]
1 ,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid [1-isopropyl-3,3-dimethyl-2-oxo-6-((S)-1-phenylethylamino)-2,3-dihydro-1H-indol-5-yl]amide [ No CAS ]

Reference： [1]Patent: WO2015/169962,2015,A1
[2]Patent: WO2019/145410,2019,A1

57
[ 89488-30-2 ]
2-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-5-isopropyl-7,7-dimethyl-3-((S)-1-phenylethyl)-5,7-dihydro-3H-imidazo[4,5-f]indol-6-one [ No CAS ]

Reference： [1]Patent: WO2015/169962,2015,A1
[2]Patent: WO2019/145410,2019,A1

58
[ 89488-30-2 ]
N-[5-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-2-methylphenyl]methanesulfonamide [ No CAS ]