[ CAS No. 846548-44-5 ] {[proInfo.proName]}

Name: 846548-44-5|(2,6-Dimethylpyridin-4-yl)boronic acid|97%
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Quality Control of [ 846548-44-5 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 846548-44-5 ]

CAS No. :	846548-44-5	MDL No. :	MFCD11042425
Formula :	C₇H₁₀BNO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	ALGDKINLACWIRM-UHFFFAOYSA-N
M.W :	150.97	Pubchem ID :	23546910
Synonyms :

Calculated chemistry of [ 846548-44-5 ]

Physicochemical Properties

Num. heavy atoms :	11
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.29
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	2.0
Molar Refractivity :	43.99
TPSA :	53.35 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.82 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	0.56
Log Po/w (WLOGP) :	-0.62
Log Po/w (MLOGP) :	-0.66
Log Po/w (SILICOS-IT) :	-0.34
Consensus Log Po/w :	-0.21

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.47
Solubility :	5.16 mg/ml ; 0.0342 mol/l
Class :	Very soluble
Log S (Ali) :	-1.25
Solubility :	8.44 mg/ml ; 0.0559 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.67
Solubility :	3.21 mg/ml ; 0.0213 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.68

Safety of [ 846548-44-5 ]

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 [ 846548-44-5 ]

* 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 [ 846548-44-5 ]
Downstream synthetic route of [ 846548-44-5 ]

[ 846548-44-5 ] Synthesis Path-Upstream 1~3

1
[ 5093-70-9 ]
[ 5419-55-6 ]
[ 846548-44-5 ]

Yield	Reaction Conditions	Operation in experiment
37%	Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78 - 20℃; for 1 h; Stage #2: With hydrogenchloride In tetrahydrofuran; hexane; water at 20℃; for 0.5 h;	A 2.5 M solution of n-BuLi in hexanes (0.26 mL, 0.65 mmol) was added to a THF solution (5 mL) of 4-bromo-2,6-dimethylpyridine (100 mg, 0.54 mmol) and triisopropylborate (149 µL, 0.65 mmol) at -78 ^oC. The reaction mixture was warmed up to rt and stirred for 1h. 1 N HCl was added and the reaction was stirred at rt for 30 minutes.1 N NaOH was added to basify and the mixture was extracted with EtOAc (3x). The combined organics were dried with Na₂SO₄, filtered and concentrated under vacuum, resulting in the title compound (30.0 mg, 0.20 mmol, 37percent) as white solid.
37%	With n-butyllithium In tetrahydrofuran; hexane at -78 - 20℃; for 1 h;	A 2.5 M solution of n-BuLi in hexanes (0.26 mL, 0.65 mmol) was added to a THF solution (5 mL) of 4-bromo-2,6-dimethylpyridine (100 mg, 0.54 mmol) and triisopropylborate (149 pL, 0.65 mmol) at -78 00. The reaction mixture was warmed up to rt and stirred for lh. 1 N HCI was added and the reaction was stirred at rt for 30 minutes. 1 N NaOH was added to basify and the mixture was extracted with EtOAc (3x). The combined organics were dried with Na2SO4, filtered and concentrated under vacuum, resulting in the title compound (30.0 mg, 0.20 mmol, 37percent) as white solid.

Reference： [1] Patent: WO2016/196644, 2016, A1, . Location in patent: Paragraph 243; 244
[2] Patent: WO2018/102452, 2018, A2, . Location in patent: Paragraph 227; 228

2
[ 5093-70-9 ]
[ 846548-44-5 ]

Reference： [1] Patent: WO2006/89054, 2006, A1, . Location in patent: Page/Page column 59; 61
[2] Patent: WO2005/19228, 2005, A1, . Location in patent: Page/Page column 62-64
[3] Patent: WO2008/156739, 2008, A1,

3
[ 13603-44-6 ]
[ 846548-44-5 ]

Reference： [1] Patent: WO2008/156739, 2008, A1,

[ 846548-44-5 ] Synthesis Path-Downstream 1~42

1
[ 846548-44-5 ]
[ 875126-15-1 ]
7-(2,6-dimethyl-pyridin-4-yl)-9-ethyl-1-thia-2,4a-diaza-cyclopenta[<i>b</i>]naphthalene-3,4-dione [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 39 - 42

2
[ 5093-70-9 ]
[ 846548-44-5 ]

Yield	Reaction Conditions	Operation in experiment
		Butyl lithium (2M in hexanes, 0.6 ml, 1.2 mmol) is added to a solution of 4- bromo-2, 6-lutidine (23, 0.2 g, 1 mmol) and triisopropyl borate (0.28 ml, 1.2 mmol) in solution of toluene (1.6 ml) and THF (0.4 ml) over 10 min at -40 C under helium. The reaction is stirred at -40 C for 30 minutes and then warmed to -20 C. 2N HCl (1 ml) is added to quench the reaction. The mixture is warmed to room temperature. The aqueous layer is collected and neutralized using 5M NaOH. NaCl (approximately 0.4 g) is added. The aqueous layer is extracted with THF (3x10 ml), and the extracts are evaporated to dryness, yielding white solid 4- (2,6-dimethylpyridyl) boronic acid (24). 1H NMR (300 MHz, DMSOd6) delta 2.5 (s, 6H), 7.34 (s, 2H). MS, m/z 152 (M+l).
	With n-butyllithium; Triisopropyl borate; In tetrahydrofuran; hexane; toluene; at -40℃; for 0.666667h;	Butyl lithium (2M in hexanes, 0. 6 ml, 1. 2 mmol) is added to a solution of 4- bromo-2, 6-lutidine (23, 0. 2 g, 1 mmol) and triisopropyl borate (0. 28 ml, 1. 2 mmol) in solution OF TOLUENE (1. 6 ml) and THF (0. 4 ml) over 10 min at-40 C under helium. The reaction is stirred at-40 C for 30 minutes and then warmed TO-20 C. 2N HCl (1 ml) is added to quench the reaction. The mixture is warmed to room temperature. The aqueous layer is collected and neutralized using 5M NAOH. NACL (approximately 0. 4 g) is added. The aqueous layer is extracted with THF (3X10 ml), and the extracts are evaporated to dryness, yielding white solid 4- (2, 6-dimethylpyridyl) boronic acid (24). 1H NMR (300 MHz, DMSO- d6) 5 2. 5 (s, 6H), 7. 34 (s, 2H). MS, m/z 152 (M+1).

Reference： [1]Patent: WO2006/89054,2006,A1 .Location in patent: Page/Page column 59; 61
[2]Patent: WO2005/19228,2005,A1 .Location in patent: Page/Page column 62-64
[3]Patent: WO2008/156739,2008,A1

3
[ 846548-44-5 ]
[ 846563-96-0 ]
9-cyclopropyl-7-(2,6-dimethyl-pyridin-4-yl)-6-fluoro-9H-isothiazolo[5,4-b]quinoline-3,4-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With water; sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 130℃; for 0.166667h;Sealed vessel; Microwave irradiation;	A mixture of tert-butyl 7-bromo-9-cyclopropyl-6-fluoro-3,4-dioxoisothiazolo[5,4- b]quinoline-2(3H,4H,9H)-carboxylate (8, 22 nig, 0.048 mmol), 4-(2,6-Dimethylpyridyl)boronic acid (5, 23 mg, 0.12 mmol) and Pd (PPh3)4 (4 mg) in a solution of DMF (1 ml) and IM NaHCO3 (0.22 ml) is sealed in a microwave reaction vessel with a stirrer. After filling with helium, the mixture is microwaved at 10OW, 130 C for 10 minutes. The reaction is followed by LC-MS. The reaction mixture is filtered and the filtrate evaporated to dryness. The residue is washed with a solution of methanol and ethyl ether (5:95) (3 x 3 ml), and dried in vacuum yielding pure product 25. 1H NMR (300 MHz, DMSO-Jtf) delta 1.1 - 1.3 (m, 4H, -CH2-), 1.53 (s, IH, -CH-), 2.47 (s, 6H, -CH3), 7.27 (s, 2H, Ar), 7.93, (d, IH, Ar), 8.2 (d, IH, Ar). 19F NMR (350 MHz, DMSO- d6) delta 125 (s, IF). MS, m/z 382 (M+l).
	With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In DMF (N,N-dimethyl-formamide); at 130℃; for 0.166667h;Microwave;	A mixture of tert-butyl 7-bromo-9-cyclopropyl-6-fluoro-3, 4- dioxoisothiazolo [5, 4-B] quinoline-2 (3H, 4H, 9H)-carboxylate (8, 22 mg, 0. 048 mmol), 4- (2, 6- Dimethylpyridyl) boronic acid (5, 23 mg, 0. 12 mmol) and Pd (PPh3) 4 (4 mg) in a solution of DMF (1 ml) and 1M NAHC03 (0. 22 ml) is sealed in a microwave reaction vessel with a stirrer. After filling with helium, the mixture is microwaved at 100W, 130 C for 10 minutes. The reaction is followed by LC-MS. The reaction mixture is filtered and the filtrate evaporated to dryness. The residue is washed with a solution of methanol and ethyl ether (5 : 95) (3 x 3 ml), and dried in vacuum yielding pure product 25. 1H NMR (300 MHz, DMSO-d6) 5 1. 1-1. 3 (m, 4H,-CH2-), 1. 53 (s, 1H,-CH-), 2. 47 (s, 6H,-CH3), 7. 27 (s, 2H, Ar), 7. 93, (d, 1H, Ar), 8. 2 (d, 1H, Ar). 19F NMR (350 MHz, DMSO-D6) 5 125 (s, 1F). MS, m/z 382 (M+1).

Reference： [1]Patent: WO2006/89054,2006,A1 .Location in patent: Page/Page column 59; 61
[2]Patent: WO2005/19228,2005,A1 .Location in patent: Page/Page column 62; 64

4
[ 846548-44-5 ]
[ 875126-15-1 ]
7-(2,6-dimethylpyridin-4-yl)-9-ethyl-1-thia-2,4a-diaza-cyclopenta[b]naphthalene-3,4-dione trifluoroacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 4; 7-(2,6-DIMETHYLPYRIDIN-4-YL)-9-ETHYL-1-THIA-2,4A-DIAZA- CYCLOPENTA[B]NAPHTHALENE-3,4-DIONE HYDROCHLORIDE (9); Tetrakis(triphenylphosphine)palladium(0) (25.9 mg, 0.022 mmol), 2,6-dimethyl- 4-pyridinylboronic acid (112.8 mg, 0.747 mmol), and a 1 M aqueous solution of sodium bicarbonate (2.3 mL, 2.3 mmol) are added sequentially under an atmosphere of argon, to a solution containing 7-chloro-9-ethyl-l-thia-2,4a-diazacyclopenta[b]naphthalene-3,4-dione (42.0 mg, 0.150 mmol) and dimethylformamide (4.0 mL). The resulting orange mixture is irradiated in a microwave for 15 min (110 C; 300 W) to give a red mixture. The solvent is evaporated under reduced pressure (~10 mm Hg, 50 0C), and the remaining solid washed with diethyl ether (3 x 15 mL). The product is extracted from this solid using hot dimethyl sulfoxide (5 x 2 mL) and purified by preparative HPLC. The purified product is isolated as the trifluoroacetate salt and converted to the hydrochloride salt by addition of a solution of hydrogen chloride (~1.25 M in methanol) followed by evaporation to give a deep red solid; this process is repeated twice.

Reference： [1]Patent: WO2006/74317,2006,A1 .Location in patent: Page/Page column 50-51

5
C₁₃H₂₂BNO₂ [ No CAS ]
[ 846548-44-5 ]

Yield	Reaction Conditions	Operation in experiment
		4-Bromo-2,6-dimethyl-pyridine (910 mg, 4.9 mmol) and triisoprqpyl borate (2.3 ml_, JO mmol). in THF. (10 mL) were cooled in a -78 C bath. BuLi (2.7 M, 7 ml_) was . added in drop wise. After 3 hrs, the bath was removed. The reaction was acidified with 1 N HCI till pH =1. The separated aqueous layer was neutralized with NaOH and subsequently extracted with ethyl acetate. A crude white solid was obtained (800mg) as the title compound.

Reference： [1]Patent: WO2008/156739,2008,A1 .Location in patent: Page/Page column 228

6
[ 846548-44-5 ]
[ 1321517-59-2 ]
[ 1321514-52-6 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 1898 - 1903

7
[ 846548-44-5 ]
[ 1391979-23-9 ]
[ 1392099-60-3 ]

Yield	Reaction Conditions	Operation in experiment
52%	With sodium carbonate;[1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); In 1-methyl-pyrrolidin-2-one; water; at 120℃; for 0.25h;microwave irradiation;	To a mixture of 100 mg (0.29 mmol) E-l, 52 mg (0.34 mmol) (2,6-dimethylpyridine-4-yl) boronic acid and 0.70 mL (1.4 mmol) of a 2 M aqueous solution of sodium carbonate in 0, 5 mL NMP i s added 12 mg ( 1 6 muiotaetaomicron ) [ 1 , r-bis(diphenylphosphino)ferrocene]- dichloropalladium(II) and the reaction mixture is stirred at 120C for 15 min under microwave irradiation. The product is purified with RP HPLC. Yield: 62.1 mg (52%). HPLC-MS: M+H = 422; tR = 1.03 min.
52%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1-methyl-pyrrolidin-2-one; water; at 120℃; for 0.25h;Microwave irradiation;	To a mixture of 100 mg (0.29 mmol) E-1, 52 mg (0.34 mmol) (2,6-dimethylpyridine-4-yl) boronic acid and 0.70 mL (1.4 mmol) of a 2 M aqueous solution of sodium carbonate in 0.5 mL NMP is added 12 mg (16 mumol) [1,1'-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) and the reaction mixture is stirred at 120 C. for 15 min. under microwave irradiation. The product is purified with RP HPLC. Yield: 62.1 mg (52%). HPLC-MS: M+H=422; tR=1.03 min

Reference： [1]Patent: WO2012/101184,2012,A1 .Location in patent: Page/Page column 71
[2]Patent: US2013/23533,2013,A1 .Location in patent: Paragraph 0302; 0303

8
[ 846548-44-5 ]
[ 1446819-44-8 ]
[ 1446819-51-7 ]

Yield	Reaction Conditions	Operation in experiment
89%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 75℃;Inert atmosphere;	A 25 mL round-bottom flask maintained with an inert atmosphere of nitrogen was charged with tert-butyl 4-[(4-bromo-2-methylphenyl)methyl]piperazine-l-carboxylate (368 mg, 1.00 mmol, 1.00 equiv), <strong>[846548-44-5](2,6-dimethylpyridin-4-yl)boronic acid</strong> (300 mg, 1.99 mmol, 1.99 equiv), Pd(PPh3)4 (1 16 mg, 0.100 mmol, 0.10 equiv), potassium carbonate (414 mg, 3.00 mmol, 3.01 equiv), dioxane (6 mL) and water (1 mL). The resulting solution was stirred overnight at 75 C. The reaction progress was monitored by LCMS. The reaction was then quenched by the addition of water (10 mL). The resulting solution was extracted with ethyl acetate (3 x 10 mL) and the organic layers were combined, washed with brine (2 x 10 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was chromatographed on a silica gel column with ethyl acetate/petroleum ether (1/1) to yield 350 mg (89% yield) of tert-butyl 4-[[4-(2,6-dimethylpyridin-4-yl)-2- methylphenyl]methyl]piperazine-l-carboxylate as yellow oil. LCMS (ESI, m/z): 396 [M+H]+.
89%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 75℃;Inert atmosphere;	Step 2: Preparation of tert-butyl 4-[[4-(2,6-dimethylpyridin-4-yl)-2- methylphenyl]methyl]piperazine-l-carboxylate [00304] A 25-mL round-bottom flask maintained with an inert atmosphere of nitrogen was charged with tert-butyl 4-[(4-bromo-2-methylphenyl)methyl]piperazine-l-carboxylate (368 mg, 1.00 mmol, 1.00 equiv), <strong>[846548-44-5](2,6-dimethylpyridin-4-yl)boronic acid</strong> (300 mg, 1.99 mmol, 1.99 equiv), Pd(PPh3)4 (116 mg, 0.100 mmol, 0.10 equiv), potassium carbonate (414 mg, 3.00 mmol, 3.01 equiv), dioxane (6 mL), and water (1 mL). The resulting solution was stirred overnight at 75 C. Reaction progress was monitored by LCMS. The reaction was then quenched by the addition of water (10 mL). The resulting solution was extracted with ethyl acetate (3 x 10 mL), and the organic layers were combined, washed with brine (2 x 10 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was chromatographed on a silica gel column with ethyl acetate/petroleum ether (1/1) to yield 350 mg (89% yield) of tert-butyl 4-[[4-(2,6-dimethylpyridin-4-yl)-2- methylphenyl]methyl]piperazine-l-carboxylate as a yellow oil. LCMS (ESI, m/z): 396 [M+H]+.

Reference： [1]Patent: WO2013/103973,2013,A1 .Location in patent: Paragraph 00372
[2]Patent: WO2013/142307,2013,A1 .Location in patent: Paragraph 00304

9
[ 846548-44-5 ]
8-bromo-4-methyl-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one [ No CAS ]
8-(2,6-dimethyl-pyridin-4-yl)-4-methyl-2-phenyl-4H-pyrazolo[1,5-a]quinazolin-5-one hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: Under inert atmosphere, a mixture of halide F, D, K or P (1.0 equiv.), boronic acid derivative R1-M G or J (1.5 equiv.), PdCI2(dppf)2 (0.1 equiv.) and aqueous Na2CO3 (1.2 M - 3.0 equiv.) in DMF (C=0.1 molL-1) was submitted to microwave irradiation (150C, 15 min, P< 70W). After cooling, the reaction mixture was filtered through a pad of celite. The pad was rinsed twice with DMSO (5 volume of DMF each time) and water was added to the filtrate (25 volume of DMF). The resulting precipitate was collected and purified by flash-chromatography. To a solution or suspension of the free base in MeOH, HCl in MeOH (1.25N, 5 equiv.) was added. The mixture was vigorously stirred, then concentrated. The residue was taken in Et2O. The resulting solid was collected, washed with Et2O and dried at 50C under reduced pressure with P2O5.

Reference： [1]Patent: WO2013/174822,2013,A1 .Location in patent: Page/Page column 72; 74; 88

10
[ 846548-44-5 ]
(R)-1-bromo-3-(4-chloro-3-methoxyphenyl)-6-methyl-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine [ No CAS ]
[ 1623763-83-6 ]

Yield	Reaction Conditions	Operation in experiment
388 mg	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 150℃; for 1h;Microwave irradiation;	(5) Synthesis of (R)-3-(4-chloro-3-methoxyphenyl)-1-(2,6-dimethylpyridin-4-yl)-6-methyl-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine A mixture of the compound obtained in Example 1-(4) (570 mg, 1.53 mmol), 2,6-dimethyl-pyridine-4-boronic acid (CAS No. 846548-44-5; 463 mg, 3.07 mmol), tetrakis(triphenylphosphine)palladium(0) (89 mg, 0.077 mg), an aqueous sodium carbonate solution (2 M, 2.3 mL) and DME (8 mL) was stirred under microwave irradiation at 150 C. for 1 hour. Water and ethyl acetate were added to the mixture. The organic layer was separated, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resultant residue was purified by silica gel column chromatography (n-heptane/ethyl acetate?ethyl acetate/methanol) to obtain a title compound (388 mg, 0.975 mmmol). 1H-NMR (400 MHz, CDCl3) delta (ppm): 1.27 (d, J=6.6 Hz, 3H), 2.56 (s, 6H), 3.19 (ddd, J=2.4, 10.6, 16.0 Hz, 1H), 3.37 (dd, J=3.9, 16.0 Hz, 1H), 3.63-3.70 (m, 1H), 3.75-3.82 (m, 1H), 3.94-4.01 (m, 1H), 3.97 (s, 3H), 4.19-4.28 (m, 2H), 6.93 (dd, J=2.0, 8.2 Hz, 1H), 7.18 (d, J=2.0 Hz, 1H), 7.21 (s, 2H), 7.46 (d, J=8.2 Hz, 1H). ESI-MS m/z 398 [M+H]+

Reference： [1]Patent: US2014/243316,2014,A1 .Location in patent: Paragraph 0351; 0360; 0361; 0362

11
[ 846548-44-5 ]
[ 1623767-01-0 ]
[ 1623763-89-2 ]

Yield	Reaction Conditions	Operation in experiment
750 mg	With dichloro bis((p-dimethylaminophenyl)-?-di-tert-butylphosphine)palladium(II); sodium carbonate; In water; N,N-dimethyl-formamide; at 130℃; for 2.5h;	(5) Synthesis of (R)-1-(2,6-dimethylpyridin-4-yl)-3-(3-methoxy-4-(trifluoromethyl)phenyl)-6-methyl-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine A mixture of the compound obtained in Example 7-(4) (900 mg, 2.22 mmol), 2,6-dimethyl-pyridine-4-boronic acid (402 mg, 2.67 mmol), (A-taPhos)2PdCl2 (79 mg, 0.111 mmol), an aqueous sodium carbonate solution (1 M, 5.55 mL) and DMF (20 mL) was stirred at 130 C. for 2.5 hours. The reaction mixture was cooled to room temperature, and then ethyl acetate and water were added to the mixture to separate the organic layer. The organic layer was washed with a saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate. The organic layer was concentrated under reduced pressure. The resultant residue was purified serially by silica gel column chromatography (n-heptane/ethyl acetate?ethyl acetate/methanol) and NH silica gel column chromatography (n-heptane/ethyl acetate) to obtain a title compound (750 mg, 1.74 mmol). 1H-NMR (400 MHz, CDCl3) delta (ppm): 1.28 (d, J=6.6 Hz, 3H), 2.56 (s, 6H), 3.20 (ddd, J=2.4, 10.5, 16.0 Hz, 1H), 3.38 (dd, J=4.3, 16.0 Hz, 1H), 3.64-3.71 (m, 1H), 3.76-3.84 (m, 1H), 3.96-4.05 (m, 1H), 3.97 (s, 3H), 4.20-4.31 (m, 2H), 7.03 (d, J=8.2 Hz, 1H), 7.21 (s, 2H), 7.28 (s, 1H), 7.67 (d, J=8.2 Hz, 1H). ESI-MS m/z 432 [M+H]+

Reference： [1]Patent: US2014/243316,2014,A1 .Location in patent: Paragraph 0425; 0436; 0437; 0438

12
[ 846548-44-5 ]
[ 1623767-13-4 ]
[ 1623763-96-1 ]

Yield	Reaction Conditions	Operation in experiment
104 mg	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 150℃; for 1h;Microwave irradiation;	(3) Synthesis of (R)-3-(4-(difluoromethoxy)-3-methylphenyl)-1-(2,6-dimethylpyridin-4-yl)-6-methyl-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine A mixture of the compound obtained in Example 14-(2) (135 mg, 0.349 mmol), 2,6-dimethyl-pyridine-4-boronic acid (73.7 mg, 0.488 mmol), tetrakis(triphenylphosphine)palladium(0) (20.1 mg, 0.017 mmol), an aqueous sodium carbonate solution (1 M, 0.697 mL), and DME (3.00 mL) was stirred under microwave irradiation at 150 C. for 1 hour. The reaction mixture was cooled to room temperature and then purified serially by silica gel column chromatography (n-heptane/ethyl acetate?ethyl acetate/methanol) and NH silica gel column chromatography (n-heptane/ethyl acetate) to obtain a title compound (104 mg, 0.252 mmol). 1H-NMR (400 MHz, CDCl3) delta (ppm): 1.26 (d, J=6.7 Hz, 3H), 2.35 (s, 3H), 2.55 (s, 6H), 3.14-3.22 (m, 1H), 3.32-3.39 (m, 1H), 3.63-3.70 (m, 1H), 3.74-3.82 (m, 1H), 3.94-4.01 (m, 1H), 4.19-4.26 (m, 2H), 6.55 (t, J=73.5 Hz, 1H), 7.18 (d, J=8.4 Hz, 1H), 7.21 (s, 2H), 7.28 (dd, J=2.3, 8.4 Hz, 1H), 7.46 (d, J=1.9 Hz, 1H). ESI-MS m/z 414 [M+H]+

Reference： [1]Patent: US2014/243316,2014,A1 .Location in patent: Paragraph 0494; 0500; 0501; 0502

13
[ 846548-44-5 ]
[ 1623767-31-6 ]
[ 1623764-09-9 ]

Yield	Reaction Conditions	Operation in experiment
21 mg	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 150℃; for 0.5h;Microwave irradiation;	(3) Synthesis of (S)-3-(4-(difluoromethoxy)-3-methylphenyl)-1-(2,6-dimethylpyridin-4-yl)-6-(fluoromethyl)-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine A mixture of the compound obtained in Example 27-(2) (28 mg, 0.069 mmol), 2,6-dimethyl-pyridine-4-boronic acid (20.9 mg, 0.138 mmol), tetrakis(triphenylphosphine)palladium(0) (8.0 mg, 0.0069 mmol), an aqueous sodium carbonate solution (1 M, 0.35 mL), and DME (0.70 mL) was stirred under microwave irradiation at 150 C. for 30 minutes. Ethyl acetate was added to the mixture, then the mixture was filtered through a silica gel pad (NH silica gel), and then the filtrate was concentrated under reduced pressure. The resultant residue was purified by silica gel thin layer chromatography (ethyl acetate) to obtain a title compound (21.0 mg, 0.049 mmol). 1H-NMR (400 MHz, CDCl3) delta (ppm): 2.35 (s, 3H), 2.56 (s, 6H), 3.21 (ddd, J=2.7, 11.3, 16.4 Hz, 1H), 3.41 (dd, J=3.9, 16.0 Hz, 1H), 3.70 (t, J=11.3 Hz, 1H), 3.83-3.94 (m, 1H), 4.05 (d, J=9.0, 14.8 Hz, 1H), 4.28-4.46 (m, 2H), 4.55 (ddd, J=5.1, 9.8, 46.5 Hz, 1H), 4.55 (d, J=14.8 Hz, 1H), 6.56 (t, J=73.4 Hz, 1H), 7.17-7.21 (m, 1H), 7.21 (s, 2H), 7.33 (d, J=2.1, 8.4 Hz, 1H), 7.47 (d, J=2.0 Hz, 1H). ESI-MS m/z 432 [M+H]+

Reference： [1]Patent: US2014/243316,2014,A1 .Location in patent: Paragraph 0584; 0590; 0591; 0592

14
[ 846548-44-5 ]
[ 1623767-34-9 ]
[ 1623764-11-3 ]

Yield	Reaction Conditions	Operation in experiment
17.3 mg	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 150℃; for 0.5h;Microwave irradiation;	(3) Synthesis of (S)-1-(2,6-dimethylpyridin-4-yl)-6-(fluoromethyl)-3-(3-methoxy-4-(trifluoromethyl)phenyl)-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine A mixture of the compound obtained in Example 29-(2) (26 mg, 0.061 mmol), 2,6-dimethyl-pyridine-4-boronic acid (18.6 mg, 0.123 mmol), tetrakis(triphenylphosphine)palladium(0) (7.1 mg, 0.0061 mmol), an aqueous sodium carbonate solution (1 M, 0.40 mL), and DME (0.80 mL) was stirred under microwave irradiation at 150 C. for 30 minutes. Ethyl acetate was added to the mixture, and then the mixture was filtered through a silica gel pad (NH silica gel) and concentrated under reduced pressure. The resultant residue was purified by silica gel thin layer chromatography (ethyl acetate) to obtain a title compound (17.3 mg, 0.038 mmol). 1H-NMR (400 MHz, CDCl3) delta (ppm): 2.57 (s, 6H), 3.21 (ddd, J=2.7, 11.3, 16.4 Hz, 1H) 3.42 (dd, J=4.1, 16.2 Hz, 1H), 3.71 (t, J=11.7 Hz, 1H), 3.87-3.99 (m, 1H), 3.97 (s, 3H), 4.07 (dd, J=9.0, 14.8 Hz, 1H), 4.28-4.47 (m, 2H), 4.57 (ddd, J=4.5, 9.6, 46.1 Hz, 1H), 4.62 (d, J=14.4 Hz, 1H), 7.10 (d, J=7.8 Hz, 1H), 7.21 (s, 2H), 7.26 (s, 1H), 7.67 (d, J=7.8 Hz, 1H). ESI-MS m/z 450 [M+H]+

Reference： [1]Patent: US2014/243316,2014,A1 .Location in patent: Paragraph 0599; 0605; 0606; 0607

15
[ 846548-44-5 ]
[ 1623767-38-3 ]
[ 1623767-39-4 ]

Yield	Reaction Conditions	Operation in experiment
175 mg	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 120℃; for 1h;Microwave irradiation;	(3) Synthesis of (R)-3-(3-chloro-4-(methoxymethoxy)phenyl)-1-(2,6-dimethylpyridin-4-yl)-6-methyl-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine A mixture of the compound obtained in Example 32-(2) (200 mg, 0.498 mmol), <strong>[846548-44-5]2,6-dimethylpyridine-4-boronic acid</strong> (120 mg, 0.797 mmol), tetrakis(triphenylphosphine)palladium(0) (43.2 mg, 0.0370 mmol), an aqueous sodium carbonate solution (2 M, 0.80 mL) and DME (1.7 mL) was stirred under microwave irradiation at 120 C. for 1 hour. The reaction mixture was cooled to room temperature and water and ethyl acetate were added to separate the organic layer. The resultant organic layer was washed with a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resultant residue was purified by NH silica gel column chromatography (n-heptane/ethyl acetate). The resultant was further purified by silica gel chromatography (ethyl acetate/methanol) to obtain a title compound (175 mg, 0.409 mmol). 1H-NMR (400 MHz, CDCl3) delta (ppm): 1.23-1.32 (m, 3H), 2.55 (s, 6H), 3.10-3.25 (m, 1H), 3.29-3.40 (m, 1H), 3.55 (s, 3H), 3.60-3.71 (m, 1H), 3.73-3.85 (m, 1H), 3.91-4.04 (m, 1H), 4.17-4.28 (m, 2H), 5.31 (s, 2H), 7.20 (s, 2H), 7.27 (d, J=8.6 Hz, 1H), 7.33 (dd, J=2.0, 8.6 Hz, 1H), 7.59 (d, J=2.0 Hz, 1H).

Reference： [1]Patent: US2014/243316,2014,A1 .Location in patent: Paragraph 0623; 0628; 0629

16
[ 846548-44-5 ]
[ 1623767-10-1 ]

Reference： [1]Patent: US2014/243316,2014,A1

17
[ 846548-44-5 ]
[ 1623763-95-0 ]

Reference： [1]Patent: US2014/243316,2014,A1

18
[ 846548-44-5 ]
[ 1623767-11-2 ]

Reference： [1]Patent: US2014/243316,2014,A1

19
[ 846548-44-5 ]
(4S)-7-chloro-N-(pyrazin-2-yl)-3,4-dihydro-1,4-methanopyrido[2,3-b][1,4]diazepine-5(2H)-carboxamide [ No CAS ]
(9S)-5-(2,6-dimethylpyridin-4-yl)-N-(pyrazin-2-yl)-1,6,8-triazatricyclo[7.2.1.0^2,7]dodeca-2,4,6-triene-8-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48.3%	With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); XPhos; In water; butan-1-ol; at 28 - 100℃; for 3h;Inert atmosphere;	Tripotassium phosphate (804 mg, 3.79 mmol) was added to a stirred solution of (4S)-7-chloro-N-(pyrazin-2-yl)-3,4-dihydro-1,4-methanopyrido[2,3-b][1,4]diazepine-5(2H)-carboxamide (600 mg, 1.894 mmol), <strong>[846548-44-5](2,6-dimethylpyridin-4-yl)boronic acid</strong> (343 mg, 2.273 mmol) in 1-butanol (10 mL), and water (1.667 mL) at 28 C. The reaction mixture was degassed for 15 min, was added Pd2(dba)3 (87 mg, 0.095 mmol), and X-phos (90 mg, 0.189 mmol). The reaction mixture was further degassed for 15 min, and the reaction mixture was stirred for 3 hr at 100 C. The reaction mixture was cooled to 28 C. and was partitioned between water (10 mL) and EtOAc (25 mL). Organic layer was separated and was dried over anhydrous Na2SO4, filtered and filtrate was evaporated to give crude as brown solid (TLC eluent: 10% MeOH in EtOAc; Rf=0.3; UV active). The crude was purified by column chromatography using (100-200 mesh) silica gel and was eluted with 5-10% MeOH in EtOAc to afford pure (4S)-7-(2,6-dimethylpyridin-4-yl)-N-(pyrazin-2-yl)-3,4-dihydro-1,4-methanopyrido[2,3-b][1,4]diazepine-5(2H)-carboxamide (355 mg, 0.916 mmol, 48.3% yield) as pale yellow solid, LCMS (m/z): 387.44 [M+H]+. 1H NMR (DMSO-d6, 400 MHz,): delta 13.77 (s, 1H), 9.43 (d, J=1.5 Hz, 1H), 8.53-8.28 (m, 2H), 7.91-7.59 (m, 4H), 5.51 (dd, J=6.0, 3.1 Hz, 1H), 3.25-2.81 (m, 4H), 2.56-2.46 (m, 6H), 2.26 (dddd, J=13.7, 9.9, 6.1, 3.7 Hz, 1H), 1.97 (dq, J=14.4, 7.5, 6.8 Hz, 1H).
48.3%	With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); XPhos; In water; butan-1-ol; at 28 - 100℃; for 3h;	Tripotassium phosphate (804 mg, 3.79 mmol) was added to a stirred solution of (4S)-7- chloro-N-(pyrazin-2-yl)-3,4-dihydro-l,4-methanopyrido[2,3-^][l,4]diazepine-5(2H)- carboxamide (600 mg, 1.894 mmol), <strong>[846548-44-5](2,6-dimethylpyridin-4-yl)boronic acid</strong> (343 mg, 2.273 mmol) in 1-butanol (10 mL), and water (1.667 mL) at 28 C. The reaction mixture was degassed for 15 min, was added Pd2(dba)3 (87 mg, 0.095 mmol), and X-phos (90 mg, 0.189 mmol). The reaction mixture was further degassed for 15 min, and the reaction mixture was stirred for 3 hr at 100 C. The reaction mixture was cooled to 28 C and was partitioned between water (10 mL) and EtOAc (25 mL). Organic layer was separated and was dried over anhydrous Na2S04, filtered and filtrate was evaporated to give crude as brown solid (TLC eluent: 10% MeOH in EtOAc; R = 0.3; UV active). The crude was purified by column chromatography using (100-200 mesh) silica gel and was eluted with 5-10% MeOH in EtOAc to afford pure (45)-7-(2,6-dimethylpyridin-4-yl)-N-(pyrazin-2- yl)-3,4-dihydro-l,4-methanopyrido[2,3-^][l,4]diazepine-5(2H)-carboxamide (355 mg, 0.916 mmol, 48.3 % yield) as pale yellow solid, LCMS (m/z): 387.44 [M+H]+.1H NMR (DMSO 400 MHz,): delta 13.77 (s, 1H), 9.43 (d, J = 1.5 Hz, 1H), 8.53 - 8.28 (m, 2H), 7.91 - 7.59 (m, 4H), 5.51 (dd, J = 6.0, 3.1 Hz, 1H), 3.25 - 2.81 (m, 4H), 2.56 - 2.46 (m, 6H), 2.26 (dddd, J= 13.7, 9.9, 6.1, 3.7 Hz, 1H), 1.97 (dq, J= 14.4, 7.5, 6.8 Hz, 1H).

Reference： [1]Patent: US2015/152108,2015,A1 .Location in patent: Paragraph 1091; 1092; 1093
[2]Patent: WO2016/79709,2016,A1 .Location in patent: Page/Page column 428

20
[ 5093-70-9 ]
[ 5419-55-6 ]
[ 846548-44-5 ]

Yield	Reaction Conditions	Operation in experiment
37%		A 2.5 M solution of n-BuLi in hexanes (0.26 mL, 0.65 mmol) was added to a THF solution (5 mL) of 4-bromo-2,6-dimethylpyridine (100 mg, 0.54 mmol) and triisopropylborate (149 muL, 0.65 mmol) at -78 oC. The reaction mixture was warmed up to rt and stirred for 1h. 1 N HCl was added and the reaction was stirred at rt for 30 minutes.1 N NaOH was added to basify and the mixture was extracted with EtOAc (3x). The combined organics were dried with Na2SO4, filtered and concentrated under vacuum, resulting in the title compound (30.0 mg, 0.20 mmol, 37%) as white solid.
37%	With n-butyllithium; In tetrahydrofuran; hexane; at -78 - 20℃; for 1h;	A 2.5 M solution of n-BuLi in hexanes (0.26 mL, 0.65 mmol) was added to a THF solution (5 mL) of 4-bromo-2,6-dimethylpyridine (100 mg, 0.54 mmol) and triisopropylborate (149 pL, 0.65 mmol) at -78 00. The reaction mixture was warmed up to rt and stirred for lh. 1 N HCI was added and the reaction was stirred at rt for 30 minutes. 1 N NaOH was added to basify and the mixture was extracted with EtOAc (3x). The combined organics were dried with Na2SO4, filtered and concentrated under vacuum, resulting in the title compound (30.0 mg, 0.20 mmol, 37%) as white solid.

Reference： [1]Patent: WO2016/196644,2016,A1 .Location in patent: Paragraph 243; 244
[2]Patent: WO2018/102452,2018,A2 .Location in patent: Paragraph 227; 228

21
[ 846548-44-5 ]
methyl 4-bromo-1-(4-(5-chloro-2-fluorophenyl)-5-(isopropylthio)thiazol-2-yl)-3-methyl-1H-pyrazole-5-carboxylate [ No CAS ]
1-(4-(5-chloro-2-fluorophenyl)-5-(isopropylthio)thiazol-2-yl)-4-(2,6-dimethylpyridin-4-yl)-3-methyl-1H-pyrazole-5-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
7%		In a 5 mL glass microwave vial equipped with a magnetic stirring bar and nitrogen flow at room temperature was placed methyl 4-bromo-1-(4-(5-chloro-2-fluorophenyl)-5- (isopropylthio)thiazol-2-yl)-3-methyl-1H-pyrazole-5-carboxylate (65.6 mg, 0.130 mmol), 2,6- dimethylpyridin-4-ylboronic acid (15.1 mg, 0.10 mmol) and Na2CO3 (53.0 mg, 0.50 mmol), nitrogen and vacuum cycles were performed (2x). Nitrogen gas was bubbled through a solution of dioxane/water (2 mL, 4:1) and then the solution was added to the microwave vial, followed by the addition of the catalyst Pd(PPh3)4 (11.6 mg, 0.01 mmol). The vial was capped and placed in an oil bath at 85 C for 16 h. LiOH (21.0 mg, 0.50 mmol) was added to the reaction mixture and stirred under microwave radiation at 120 oC for 10 min. The product was purified using a semi prep HPLC-MS (column X-Bridge 30x50, eluted with 30-50% MeCN/NH4CO2H 10 mM, pH 3.8/Flow 45 ml/min/11 min), resulting in the title compound (4.70 mg, 0.009 mmol, 7%) as white solid after lyophilization. 1H NMR (500 MHz, DMSO) delta 14.26 (s, 1H), 7.60 (ddd, J = 8.8, 4.3, 2.8 Hz, 1H), 7.54 (dd, J = 6.1, 2.7 Hz, 1H), 7.42 (t, J = 9.1 Hz, 1H), 7.13 (s, 2H), 3.28- 3.19 (m, J = 13.3, 6.6 Hz, 2H), 2.45 (s, 6H), 2.32 (s, 3H), 1.16 (d, J = 6.7 Hz, 6H); MS (m/z): 517.1 [M+1]+.
7%		In a 5 mL glass microwave vial equipped with a magnetic stirring bar and nitrogen flow at room temperature was placed methyl 4-bromo-1-(4-(5-chloro-2-fluorophenyl)-5- (isopropylthio)thiazol-2-yl)-3-methyl- 1 H-pyrazole-5-carboxylate (65.6 mg, 0.130 mmol), 2,6- dimethylpyridin-4-ylboronic acid (15.1 mg, 0.10 mmol) and Na2003 (53.0 mg, 0.50 mmol), nitrogen and vacuum cycles were performed (2x). Nitrogen gas was bubbled through a solution of dioxane/water (2 mL, 4:1) and then the solution was added to the microwave vial, followed by the addition of the catalyst Pd(PPh3)4 (11.6 mg, 0.01 mmol). The vial was capped and placed in an oil bath at 85 00 for 16 h. LiOH (21.0 mg, 0.50 mmol) was added to the reaction mixture and stirred under microwave radiation at 120 C for 10 mm. The product was purified using a semi prep HPLC-MS (column X-Bridge 30x50, eluted with 30-50% MeCN/NH4002H 10 mM, pH 3.8/Flow 45 mI/mm/li mm), resulting in the title compound (4.70 mg, 0.009 mmol, 7%) as white solid after lyophilization.[231] 1H NMR (500 MHz, DMSO) O 14.26 (5, 1H), 7.60 (ddd, J= 8.8, 4.3, 2.8 Hz, 1H), 7.54(dd, J= 6.1, 2.7 Hz, 1H), 7.42 (t, J= 9.1 Hz, 1H), 7.13(s, 2H), 3.28-3.19(m, J= 13.3,6.6 Hz, 2H), 2.45 (5, 6H), 2.32 (5, 3H), 1.16 (d, J= 6.7 Hz, 6H); MS (m/z): 517.1 [M+1].

Reference： [1]Patent: WO2016/196644,2016,A1 .Location in patent: Paragraph 245; 246
[2]Patent: WO2018/102452,2018,A2 .Location in patent: Paragraph 229; 230; 231

22
[ 846548-44-5 ]
[ 1110642-00-6 ]
(R)-3-((S)-1-(4-(2,6-dimethylpyridin-4-yl)phenyl)ethyl)-6-(3-hydroxypropyl)-6-phenyl-1,3-oxazinan-2-one [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 3649 - 3657

23
[ 846548-44-5 ]
[ 1110641-70-7 ]
(S)-3-((S)-1-(4-(2,6-dimethylpyridin-4-yl)phenyl)ethyl)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 3649 - 3657

24
[ 846548-44-5 ]
methyl 4-bromo-1-(4-(3,4-dichlorophenyl)-5-(isopropylthio)thiazol-2-yl)-3-methyl-1H-pyrazole-5-carboxylate [ No CAS ]
1-(4-(3,4-dichlorophenyl)-5-(isopropylthio)thiazol-2-yl)-4-(2,6-dimethylpyridin-4-yl)-3-methyl-1H-pyrazole-5-carboxylic acid [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 4471 - 4477

25
[ 13603-44-6 ]
[ 846548-44-5 ]

Reference： [1]Patent: WO2008/156739,2008,A1

26
[ 846548-44-5 ]
(R)-4-bromo-N-(1-(3-methoxyphenyl)ethyl)benzamide [ No CAS ]
(R)-4-(2,6-dimethylpyridin-4-yl)-N-(1-(3-methoxyphenyl)ethyl)benzamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 11074 - 11100

27
[ 846548-44-5 ]
6-bromo-7-phenyl-1,8-naphthyridin-2(1H)-one [ No CAS ]
6-(2,6-dimethylpyridin-4-yl)-7-phenyl-1,8-naphthyridin-2(1H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
15%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,4-dioxane; water; at 90℃; for 4h;Inert atmosphere;	To a stirred solution of 6-bromo-7-phenyl-1,8-naphthyridin-2(1H)-one (0.120 g, 0.40 mmol, 1.0 equiv) and <strong>[846548-44-5](2,6-dimethylpyridin-4-yl)boronic acid</strong> (0.073 g, 0.48 mmol, 1.2 equiv) in dioxane (2 mL) was added Na2CO3 (0.085 g, 0.80 mmol, 2.0 equiv) and 0.8 mL water. The reaction was purged with N2 for 5 min. To this reaction mixture was added Pd(dppf)Cl2-DCM complex (0.016 g, 5 mol %) and N2 was purged again for another 5 min. The reaction mixture was heated at 90 C. for 4 h. The reaction mixture was allowed to cool to RT and extracted using ethyl acetate (2*35 mL). The combined organic layers were washed (brine), dried (anhydrous Na2SO4) and concentrated under vacuum to get the solid residue which was purified by reverse phase column chromatography to get the desired product as off white solid (0.020 g, 15%). LCMS: 328 [M+1]+. 1H NMR (400 MHz, DMSO-d6) delta 12.28 (br. s., 1H), 8.22 (s, 1H), 8.00 (d, J=9.78 Hz, 1H), 7.26-7.44 (m, 5H), 6.86 (s, 2H), 6.63 (d, J=9.29 Hz, 1H), 2.32 (s, 6H)

Reference： [1]Patent: US2019/23702,2019,A1 .Location in patent: Paragraph 0465-0467

28
[ 846548-44-5 ]
6-bromo-7-phenyl-1H-1,8-naphthyridin-4-one [ No CAS ]
6-(2,6-dimethylpyridin-4-yl)-7-phenyl-1,8-naphthyridin-4(1H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
22%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,4-dioxane; water; at 90℃; for 4h;Inert atmosphere;	To a stirred solution of <strong>[846548-44-5](2,6-dimethylpyridin-4-yl)boronic acid</strong> (0.73 g, 0.48 mmol, 1.2 equiv) and 6-bromo-7-phenyl-1,8-naphthyridin-4(1H)-one (0.073 g, 0.40 mmol, 1.0 equiv) in dioxane (2 mL) was added Na2CO3 (0.085 g, 0.80 mmol, 2.0 equiv) and water 0.8 mL. The reaction was purged with N2 for 5 min. To this reaction mixture was added Pd(dppf)Cl2.DCM (0.016 g, 5 mol %) and N2 was re-purged for another 5 min. The reaction mixture was heated at 90 C. for 4 h. The reaction mixture was allowed to cool to RT and extracted using ethyl acetate (2*35 mL). The combined organic layers were washed (brine), dried (anhydrous Na2SO4) and concentrated under vacuum to get the solid residue which was purified by reverse phase column chromatography to get the desired product as off white solid (0.030 g, 22%). LCMS: 328 [M+1]+ 1H NMR (400 MHz, DMSO-d6) delta 12.37 (d, J=5.38 Hz, 1H), 8.39 (s, 1H), 7.93-8.05 (m, 1H), 7.27-7.47 (m, 5H), 6.89 (s, 2H), 6.15 (d, J=7.34 Hz, 1H), 2.33 (s, 6H).

Reference： [1]Patent: US2019/23702,2019,A1 .Location in patent: Paragraph 0250-0253

29
[ 846548-44-5 ]
(R)-tert-butyl ((5-bromoisochroman-1-yl)methyl)(methyl)carbamate [ No CAS ]
(R)-tert-butyl (5-(2,6-dimethylpyridin-4-yl)isochroman-1-yl)methyl(methyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; for 10h;Reflux;	To a solution of (R)-tert-buty (5-bromoisochroman-l-yl)methyl(methyl)carbamate (500 mg, 1.4 mmol, 1.0 eq.) in dioxane/thO (30 mL, 5: 1) was added 2,6-dimethylpyridin-4- ylboronic acid (423 mg, 2.8 mmol, 2.0 eq.), K2CO3 (580 mg, 4.2 mmol, 3.0 eq.) and (1206) Pd(PPh3)4 (161 mg, 0.14 mmol, 0.1 eq.), then stirred at reflux for 10 h, monitored by LC-MS. The mixture was concentrated, then purification by silica gel column (P.E:EA = 3: 1) to afforded (R)-tert-buty (5-(2,6-dimethylpyridin-4-yl)isochroman-l- yl)methyl(methyl)carbamate (500 mg, Yield: 93%), MS (ESI): mlz 283 [M -100 + H]+.

Reference： [1]Patent: WO2019/28165,2019,A1 .Location in patent: Paragraph 0769-0770

30
[ 846548-44-5 ]
(R)-tert-butyl ((5-bromoisochroman-1-yl)methyl)(methyl)carbamate [ No CAS ]
(R)-1-(5-(2,6-dimethylpyridin-4-yl)isochroman-1-yl)-N-methylmethanamine dihydrochloride [ No CAS ]

Reference： [1]Patent: WO2019/28165,2019,A1

31
[ 846548-44-5 ]
(S)-tert-butyl ((5-bromoisochroman-1-yl)methyl)(methyl)carbamate [ No CAS ]
(S)-tert-butyl (5-(2,6-dimethylpyridin-4-yl)isochroman-1-yl)methyl(methyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; for 10h;Reflux;	To a solution of ( (1211) Pd(PPh3)4 (161 mg, 0.14 mmol, 0.1 eq.), then stirred at reflux for 10 h, monitored by LC-MS. The reaction mixture was concentrated to dry, the residue was purified by silica gel column (P.E:EA = 3: 1) to afford (S)-tert-bu y (5-(2,6-dimethylpyridin-4-yl)isochroman-l- yl)methyl(methyl)carbamate (500 mg, Yield: 93%), MS (ESI): mlz 283 [M -100 + H]+.

Reference： [1]Patent: WO2019/28165,2019,A1 .Location in patent: Paragraph 0773-0774

32
[ 846548-44-5 ]
(S)-tert-butyl ((5-bromoisochroman-1-yl)methyl)(methyl)carbamate [ No CAS ]
(S)-1-(5-(2,6-dimethylpyridin-4-yl)isochroman-1-yl)-N-methylmethanamine dihydrochloride [ No CAS ]

Reference： [1]Patent: WO2019/28165,2019,A1

33
[ 846548-44-5 ]
5-bromo-2-(methylthio)-6-phenylpyrimidin-4-amine [ No CAS ]
5-(2,6-dimethylpyridin-4-yl)-2-(methylthio)-6-phenylpyrimidin-4-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
20%	With [1,1?-bis(di-cyclohexylphosphino)ferrocene]dichloropalladium (II); caesium carbonate; In water; tert-butyl alcohol; at 120℃; for 2h;	[l,l?~bis(dieyelohexylphosphino)ferrocenejdichloropalladium(ii) (510 mg, 10 mol%) was added to a mixture of 5-bromo-2-(methylthio)-6-phenylpyrimidin-4-amine (prepared in Example 15, Step 2) (2.0 g, 6.8 mmol), <strong>[846548-44-5](2,6-dimethylpyridin-4-yl)boronic acid</strong> (1.5 g, 10 mmol), and cesium carbonate (4.4 g, 14 mmol) in /erf-butanol (25 mL) and water (5.0 mL). The mixture was purged with nitrogen, and then stirred at 120 C for 2 h. The reaction mixture was cooled to room temperature and filtered through a Ceiite plug. The filtrate was concentrated under reduced pressure and purified by flash chromatography on a silica gel column eluting with 0-100% EtO Ac/hexanes to give the desired product (440 mg, 20%). LC- MS calculated for CI8HI9N4S (M+H)+: m/z = 323.1; found 323.1.

Reference： [1]Patent: WO2019/168847,2019,A1 .Location in patent: Page/Page column 173; 174

34
[ 846548-44-5 ]
ethyl 8-bromo-5-(2,4-dimethoxybenzylamino)-7-phenylimidazo[1,2-c]pyrimidine-2-carboxylate [ No CAS ]
ethyl 5-(2,4-dimethoxybenzylamino)-8-(2,6-dimethylpyridin-4-yl)-7-phenylimidazo[1,2-c]pyrimidine-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	With [1,1?-bis(di-cyclohexylphosphino)ferrocene]dichloropalladium (II); caesium carbonate; In water; tert-butyl alcohol; at 120℃; for 1.5h;	[l, -bis(dicyclohexylphosphino)ferrocene]dichloropalladium(II) (400 mg, 10 moi%) was added to a mixture of ethyl 8-bromo-5-((2,4-dimethoxybenzyl)amino)-7- phenylimidazo[l,2-c]pyrimidine-2-carboxyiate (prepared in Example 15, Step 4) (2.7 g, 5.3 mmol), (2,6-dimetliylpyridin-4-yl)boronic acid (1.2 g, 7.9 mmol), and cesium carbonate (3.4 g, 11 mmol) in /en'-butanol (20 mL) and water (3.8 mL). The mixture was purged with nitrogen, and then stirred at 120 C for 1.5 h. The reaction mixture was cooled to room temperature, filtered through a Celite plug with DCM and concentrated under reduced pressure. The resulting material was purified by column chromatography eluting with 0-20% MeOH/DCM to give the desired product (2.8 g, 99%). LC-MS calculated for C3JH32N5O4 (M+H)+: m/z = 538.2; found 538.3.

Reference： [1]Patent: WO2019/168847,2019,A1 .Location in patent: Page/Page column 171

35
[ 846548-44-5 ]
N-(5-bromo-2-cyclopropyl-4-(2,4-difluorophenoxy)phenyl)ethanesulfonamide [ No CAS ]
N-(2-cyclopropyl-4-(2,4-difluorophenoxy)-5-(2,6-dimethylpyridin-4-yl)phenyl)ethanesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 100℃; for 4h;Inert atmosphere;	N-(5-Bromo-2-cyclopropyl-4-(2,4-difluorophenoxy)phenyl)ethanesulfonamide (0.060 g, 0.14 mmol), (2,6-di) Methylpyridin-4-yl)boronic acid (0.042 g, 0.28 mmol), Potassium carbonate (0.038 g, 0.28 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (0.01 g, 0.014 mmol) dissolved in dioxane (4 mL) and water (1 mL), nitrogen was replaced three times, heated to 100 C, and reacted for four hours. After the reaction was completed, it was cooled to room temperature. The reaction was diluted with ethyl acetate (20mL), filtered through Celite, Celite with ethyl acetate (20mL), dried combined organic phases, the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, spin-dry The crude product was separated with a preparative plate (petroleum ether: ethyl acetate = 3:1) to give N-(2-cyclopropyl-4-(2,4-difluorophenoxy)-5-(2,6- Methylpyridin-4-yl)phenyl)ethanesulfonamide (0.06 g, pale yellow oil, yield: 70%).

Reference： [1]Patent: CN110041253,2019,A .Location in patent: Paragraph 0930-0933

36
[ 846548-44-5 ]
N-(5-bromo-2-cyclopropyl-4-(2,4-difluorophenoxy)phenyl)methanesulfonamide [ No CAS ]
N-(2-cyclopropyl-4-(2,4-difluorophenoxy)-5-(2,6-dimethylpyridin-4-yl)phenyl)methanesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 100℃; for 4h;Inert atmosphere;	N-(5-bromo-2-cyclopropyl-4-(2,4-difluorophenoxy)phenyl)methanesulfonamide (0.040 g, 0.10 mmol), (2,6-di) Methylpyridin-4-yl)boronic acid (0.10 g, 0.19 mmol), potassium carbonate (0.026 g, 0.19 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride ( 0.007 g, 0.01 mmol) was dissolved in dioxane (4 mL) and water (1 mL), replaced with nitrogen three times, heated to 100 C, and reacted for four hours. After the reaction was completed, it was cooled to room temperature. The reaction was diluted with ethyl acetate (20 mL), filtered through celite, celite washed with ethyl acetate (20 mL), the combined organic phases were washed with saturated brine (15mL * 3) The organic phase was dried over anhydrous sodium sulfate , filtration, spin-drying, and the crude product was separated with a preparative plate ( petroleum ether: ethyl acetate = 3:1) to give N-(2-cyclopropyl-4-(2,4-difluorophenoxy)-5- (2,6-Dimethylpyridin-4-yl)phenyl)methanesulfonamide (0.02 g, pale yellow oil, yield: 47%).

Reference： [1]Patent: CN110041253,2019,A .Location in patent: Paragraph 0939; 0946-0949

37
[ 846548-44-5 ]
1-(4-bromo-5-(2,4-difluorophenoxy)-2-nitrophenyl)-1H-pyrazole [ No CAS ]
4-(2-(2,4-difluorophenoxy)-5-nitro-4-(1H-pyrazol-1-yl)phenyl)-2,6-dimethylpyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 90℃; for 14h;	1-(4-Bromo-5-(2,4-difluorophenoxy)-2-nitrophenyl)-1H-pyrazole (0.050 g, 0.126 mmol, (2,6-di) at room temperature Methylpyridin-4-yl)boronic acid (0.038 g, 0.25 mmol), potassium carbonate (0.035 g, 0.25 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride ( 0.010 g, 0.013 mmol) was dissolved in dioxane (6 mL) and water (2 mL), replaced with nitrogen three times, heated to 90 C, and reacted for fourteen hours. After the reaction was completed, it was cooled to room temperature. The reaction was diluted with ethyl acetate (20 mL), filtered through celite, celite washed with ethyl acetate (20 mL), the combined organic phases were washed with saturated brine (10mL * 3) The organic phase was dried over anhydrous sodium sulfate , filtration, spin-drying, and the crude product was separated using a preparative plate ( petroleum ether: ethyl acetate = 5:1) to give 4-(2-(2,4-difluorophenoxy)-5-nitro-4-( 1H-Pyrazol-1-yl)phenyl)-2,6-lutidine (0.025 g, colorless oil, yield: 47%).

Reference： [1]Patent: CN110041253,2019,A .Location in patent: Paragraph 0955; 0962-0965

38
[ 846548-44-5 ]
tert-butyl 4-(4-bromo-5-(2,4-difluorophenoxy)-2-nitrophenyl)-3,6-dihydropyridine-1(2H)-carboxylate [ No CAS ]
tert-butyl 4-(5-(2,4-difluorophenoxy)-4-(2,6-dimethylpyridin-4-yl)-2-nitrophenyl)-3,6-dihydropyridine-1(2H)-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 20℃;	tert-butyl 4-(4-bromo-5-(2,4-difluorophenoxy)-2-nitrophenyl)-3,6-dihydropyridine-1(2H)-carboxylate(0.12 g, 0.23 mmol), (2,6-Dimethylpyridin-4-yl)boronic acid (0.071 g, 0.47 mmol), potassium carbonate (0.065 g, 0.47 mmol) and [1,1'-bis(diphenylphosphino)ferrocene Palladium dichloride (0.017 g, 0.023 mmol) was dissolved in dioxane (6 mL) and water (2 mL). After the reaction was completed, it was cooled to room temperature. The reaction was diluted with ethyl acetate (20 mL), filtered through celite, celite washed with ethyl acetate (20 mL), the combined organic phase was washed with saturated brine (10mL * 3), dried over anhydrous sodium sulfate, filtered , spin dry, the crude product was separated by preparative plate (petroleum ether: ethyl acetate = 1:1) to give tert-butyl 4-(5-(2,4-difluorophenoxy)-4-(2,6-dimethylpyridin-4-yl)-2-nitrophenyl)-3,6-dihydropyridine-1(2H)-carboxylate (0.08 g, colorless oil, yield: 63%).

Reference： [1]Patent: CN110041253,2019,A .Location in patent: Paragraph 0979; 0986-0989

39
[ 846548-44-5 ]
N-(5-bromo-4-(2,4-difluorophenoxy)-2-methylphenyl)ethanesulfonamide [ No CAS ]
N-(4-(2,4-difluorophenoxy)-5-(2,6-dimethylpyridin-4-yl)-2-methylphenyl)ethanesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 20℃;	N-(5-bromo-4-(2,4-difluorophenoxy)-2-methylphenyl)ethanesulfonamide (0.060 g, 0.15 mmol), (2,6-dimethyl) Pyridin-4-yl)boronic acid (0.054 g, 0.35 mmol), potassium carbonate (0.041 g, 0.30 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (0.011 g, 0.015 mmol) was dissolved in dioxane (6 mL) and water (2 mL). After the reaction was completed, it was cooled to room temperature. The reaction solution was extracted with ethyl acetate (20mL) was diluted, filtered through celite, celite washed with ethyl acetate (20mL), the combined organic phases, The organic phase was washed with saturated brine (15 mL*3), dried over anhydrous sodium sulfate, filtered, and evaporated. ,4-difluorophenoxy)-5-(2,6-dimethylpyridin-4-yl)-2-methylphenyl)ethanesulfonamide (0.03 g, pale yellow oil, yield: 47 %).

Reference： [1]Patent: CN110041253,2019,A .Location in patent: Paragraph 1007; 1021-1024

40
[ 846548-44-5 ]
N-(5-bromo-4-(2,4-difluorophenoxy)-2-methoxyphenyl)ethanesulfonamide [ No CAS ]
N-(4-(2,4-difluorophenoxy)-5-(2,6-dimethylpyridin-4-yl)-2-methoxyphenyl)ethanesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
59%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 20℃;	N-(5-bromo-4-(2,4-difluorophenoxy)-2-methoxyphenyl)ethanesulfonamide (0.12 g, 0.28 mmol), (2,6-di) Methylpyridin-4-yl)boronic acid (0.10 g, 0.68 mmol), potassium carbonate (0.079 g, 0.57 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride ( 0.021 g, 0.028 mmol) was dissolved in dioxane (6 mL) and water (2 mL). After the reaction was completed, it was cooled to room temperature. The reaction was diluted with ethyl acetate (20 mL), filtered through celite, celite washed with ethyl acetate (20 mL), the combined organic phase was washed with saturated brine (15mL * 3), dried over anhydrous sodium sulfate, filtered , spin dry, the crude product was separated by preparative plate to obtain N-(4-(2,4-difluorophenoxy)-5-(2,6-dimethylpyridin-4-yl)-2-methoxybenzene Ethyl sulfonamide (petroleum ether: ethyl acetate = 2:1) gave (0.075 g, pale yellow solid, yield: 59%).

Reference： [1]Patent: CN110041253,2019,A .Location in patent: Paragraph 1030; 1047-1050

41
[ 846548-44-5 ]
[ 105512-81-0 ]
4-(3-(2,6-dimethylpyridin-4-yl)phenyl)thiazol-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60.45%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate In 1,4-dioxane at 75℃; for 4h;	60.1 Step 1: Preparation of 4-(3-(2,6-dimethylpyridin-4-yl)phenyl)thiazol-2-amine (Intermediate C) To a solution of 4-(3-bromophenyl)thiazol-2-amine (600 mg, 2.35 mmol) and (2,6-dimethyl-4- pyridyl) boronic acid (532.56 mg, 3.53 mmol) in dioxane/ H2O=4/1 (10 mL) was added K3PO4 (1.50 g, 7.06 mmol) and [1,1-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) (229.91 mg, 352.76 mmol). The mixture was stirred at 75 °C under N2 for 4 h. The reaction mixture was diluted with H2O (20 mL) and extracted with EtOAc (20 mL x 2). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, Petroleum ether / EtOAc = 1/0 to 1:1) and concentrated in vacuum to give Intermediate C (400 mg, 1.42 mmol, 60.45% yield) as a yellow solid. LCMS (ESI) m/z [M+H]+ =282.0; 1H NMR (400 MHz, Methanol-d4) d 8.11 (m, 1H), 7.83-7.81 (m, 1H), 7.61 (m, 1H), 7.50-7.48 (m, 1H), 7.42 (s, 2H), 6.96 (s, 1H), 2.56 (s, 6H).

Reference： [1]Current Patent Assignee: FOGHORN THERAPEUTICS INC - WO2020/160180, 2020, A1 Location in patent: Page/Page column 173-174

42
[ 846548-44-5 ]
[ 1219741-50-0 ]
6-(2,6-dimethyl-4-pyridyl)-3-methyl-1H-indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With [2-(2-aminophenyl)phenyl]-chloro-palladium-dicyclohexyl-[3-(2,4,6-triisopropylphenyl)phenyl]phosphane; Cs₂CO₃ In 1,4-dioxane; lithium hydroxide monohydrate at 110℃; for 2h; Inert atmosphere;	Preparation of Intermediate I-5 6-(2,6-dimethyl-4-pyridyl)-3-methyl-1H-indole: To 250 ml RBF was added 6- bromo-3-methyl-1H-indole (4.00 g, 19.0 mmol), 2,6-dimethyl-4-pyridyl)boronic acid (3.20 g, 20.9 mmol), XPhos Pd G2 (748 mg, 0.95 mmol), 10:1 dioxane and water (100 ml) and cesium carbonate (15.50 g, 47.6 mmol). The solution was degassed by bubbling argon for 30 seconds, then heated at 110 °C for 2 hours. The reaction mixture was cooled, filtered through Celite (eluent: EtOAc), and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: EtOAc / Hex) to provide the desired product. ES/MS: 237.2 (M+H+).

Reference： [1]Current Patent Assignee: GILEAD SCIENCES INC - WO2022/140326, 2022, A1 Location in patent: Paragraph 0614

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H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 846548-44-5 ] {[proInfo.proName]}

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[ 846548-44-5 ] Synthesis Path-Upstream 1~3

[ 846548-44-5 ] Synthesis Path-Downstream 1~42

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Organoboron

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Pyridines

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