[ CAS No. 458532-97-3 ] {[proInfo.proName]}

Name: 458532-97-3|(3-Fluoropyridin-4-yl)boronic acid|95%
Brand: Ambeed
SKU: A214394
Rating: 97 (32 reviews)

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Quality Control of [ 458532-97-3 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 458532-97-3 ]

Product Details of [ 458532-97-3 ]

CAS No. :	458532-97-3	MDL No. :	MFCD03788558
Formula :	C₅H₅BFNO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	QUHSESYLMZVXCN-UHFFFAOYSA-N
M.W :	140.91	Pubchem ID :	2779353
Synonyms :

Calculated chemistry of [ 458532-97-3 ]

Physicochemical Properties

Num. heavy atoms :	10
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	4.0
Num. H-bond donors :	2.0
Molar Refractivity :	34.02
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) :	-7.26 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	-0.14
Log Po/w (WLOGP) :	-0.68
Log Po/w (MLOGP) :	-0.93
Log Po/w (SILICOS-IT) :	-0.72
Consensus Log Po/w :	-0.49

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.0
Solubility :	14.0 mg/ml ; 0.0992 mol/l
Class :	Very soluble
Log S (Ali) :	-0.53
Solubility :	41.9 mg/ml ; 0.298 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.17
Solubility :	9.57 mg/ml ; 0.0679 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.85

Safety of [ 458532-97-3 ]

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

Application In Synthesis of [ 458532-97-3 ]

* 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 [ 458532-97-3 ]
Downstream synthetic route of [ 458532-97-3 ]

[ 458532-97-3 ] Synthesis Path-Upstream 1~2

1
[ 458532-97-3 ]
[ 22282-73-1 ]

Yield	Reaction Conditions	Operation in experiment
75%	With copper(ll) sulfate pentahydrate; ellagic acid In methanol at 60℃; for 8 h; Green chemistry	General procedure: In a typical reaction, 10 molpercent CuSO4·5H2O, (0.049 g, 0.2 mmol)and 6.7 molpercent EA (20 mg) were mixed in methanol followed by2 mmol of phenylboronic acid. This reaction mixture was kept ina preheated oil bath by maintaining the temperature at 60 °C andstirred under atmospheric pressure. After completion of the reac-tion, modified by TLC, the mixture was washed twice with hot ethylacetate to remove the reactant and product. The hot ethyl acetatewas removed from the reaction mixture and the resulting crudeproduct was purified by a column chromatography using silicagel 260 mesh (pet ether:ethyl acetate) ratio (25:75). The recov-ered catalyst was reused for the next run. All the products werecharacterized by1H and13C NMR spectra.

Reference： [1] Journal of Molecular Catalysis A: Chemical, 2014, vol. 395, p. 500 - 505

2
[ 372-47-4 ]
[ 458532-97-3 ]

Reference： [1] Tetrahedron, 2002, vol. 58, # 22, p. 4369 - 4373

[ 458532-97-3 ] Synthesis Path-Downstream 1~48

1
[ 372-47-4 ]
[ 458532-97-3 ]

Reference： [1]Tetrahedron,2002,vol. 58,p. 4369 - 4373

2
[ 52522-99-3 ]
[ 458532-97-3 ]
[ 952402-66-3 ]

Yield	Reaction Conditions	Operation in experiment
93%	With sodium carbonate;palladium diacetate; triphenylphosphine; In propan-1-ol; for 1.5h;Heating / reflux;	Preparation 66: 5-(3-Fluoro-pyridin-4-yl)-2,4-dimethoxy-pyrimidine (Prep66); <n="98"/>5-lodo-2,4-dimethoxy-pyrimidine (commercially avaialble from Matrix, 905 mg, 3.4 mmol) was dissolved in degassed n-PrOH (24 ml) and then 3-fluoropyridine-4-boronic acid (715 mg, 5.1 mmol), Na2CO3 (721 mg, 6.8 mmol), PPh3 (84 mg, 0.34 mmol) and Pd(OAc)2 (40 mg) were added. The suspension was stirred at reflux for 1.5 hours. The solvent was evaporated under vacuum and the crude was partitioned between water and ethyl acetate.The organic phase was dried (Na2SO4) and evaporated. The crude was purified by flash chromatography with DCM-MeOH 98-2 and by SCX cartridge washing with MeOH and then collecting the product with MeOH-NH4OH (95-5) to give 750 mg of the title compound (93percent yield).MS (ES) (mlz): 236.2 [M+H]+.

Reference： [1]Patent: WO2007/113232,2007,A1 .Location in patent: Page/Page column 95-96

3
[ 2891-10-3 ]
[ 458532-97-3 ]
7-(3-fluoro-4-pyridinyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;bis-triphenylphosphine-palladium(II) chloride; In water; N,N-dimethyl-formamide; at 150℃; for 0.08333330000000001h;Microwave irradiation;	Example 17, Step 3: 7-(3-fluoropyridin-4-yl)-5-phenyl-2,3-dihydro-1H-1,4- benzodiazepine. A 5mL microwave tube was charged with 7-bromo-5-phenyl-2,3-dihydro-1/-/-1 ,4- benzodiazepine (50mg), dimethylformamide (3.5mL), <strong>[458532-97-3]3-fluoro-4-pyridylboronic acid</strong> (2 equiv), potassium carbonate (2 equiv), bis(triphenylphosphine)-palladiurndich loride (10 mol percent), and water (0.7mL). The mixture was heated in a microwave at 1500C for 5 min, then cooled and concentrated to dryness. The residue was taken up in ethyl acetate and filtered through a Celite pad. The filtrate was concentrated to dryness and the residue was triturated in diethyl ether. The resulting solids were collected on filter then purified using preparative thin-layer chromatography. The plates were eluted with 12.5percent methanol in chloroform, and the desired band was collected to provide 7-(3-fluoropyridin-4-yl)-5-phenyl-2,3-dihydro-1/-/-1 ,4-benzodiazepine as a EPO <DP n="53"/>yellow powder. H1 NMR (d6-dmso): 8.45 (d, 1 H), 8.32 (d, 1 H), 7.52 (d, 1 H), 7.46 (m, 2H), 7.36-7.42 (m, 4H), 7.21 (s, 1 H), 6.91 (d, 1 H), 6.78 (br t, 1 H), 3.96 (m, 2H), 3.60 (m, 2H).

Reference： [1]Patent: WO2006/44753,2006,A2 .Location in patent: Page/Page column 51-52

4
[ 887374-79-0 ]
[ 458532-97-3 ]
(4-chloro-3-fluoro-benzyl)-(3'-fluoro-[3,4']bipyridinyl-5-yl)-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,2-dimethoxyethane; water; at 90℃;	Synthesis of (4-Chloro-3-fluoro-benzyl)-(3'-fluoro-[3Lambda4'] bipyridinyl-5-yl)-amine; EPO <DP n="41"/>To a solution of (5-Bromo-pyridin-3-yl)-(4-chloro-3-fluoro-benzyl)-amine (lOOmg, 0.32mmol) in DME/H2O (3: 1) (8ml) was added under a nitrogen atmosphere the boronic acid (83mg, 0.47mmol) and NaHCO3 (53mg, 0.64mmol). Pd(dppf)CI2 (26mg, 0.03mmol) was then added to the reaction mixture and heated at 9O0C stirring overnight. The reaction mixture was diluted with ethyl acetate, washed with water, dried (MgSO4), evaporated and purified on silica gel by flash chromatography eluting with DCM:MeOH (95:5) to give the desired product (31mg). IH (400MHz, CDCI3) 4.35-4.42 (IH, bs, NH), 4.40-4.42 (2H, m), 7.05-7.20 (2H, m, Ar), 7.34-7.41 (2H, m, Ar), 8.11-8.12 (2H, m, Ar), 8.21 (IH, s, Ar), 8.47-8.49 (IH, m, Ar), 8.55 (IH, s, Ar); m/z: 332 (M + l).

Reference： [1]Patent: WO2006/51311,2006,A1 .Location in patent: Page/Page column 39-40

5
[ 1044920-83-3 ]
[ 458532-97-3 ]
tert-butyl 4-[6-(4-chlorophenyl)-5-(3-fluoropyridin-4-yl)pyrazin-2-yl]piperazine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 100℃; for 16.0h;Product distribution / selectivity;	EXAMPLE 13. GENERAL PROCEDURE FOR THE SUZUKI REACTION OF ARYL BORONIC ACIDS WITH tert-BUTYL-4-[5-BROMO-6-(4-CHLOROPHENYL)-PYRAZIN-2-YL]-PIPERAZINE-l-CARBOXyLATEArylboronic acid (0.21 mmol) is added to a solution of tert-butyl-4-[5-bromo-(6- chlorophenyl)-pyrazin-2-yl]-piperazine-l-carboxylate (80 mg, 0.18 mmol) in a mixture of dioxane (3 mL), water (0.5 mL) and 2N sodium carbonate solution (0.18 mL, 0.36 mmol). The solution is degassed by bubbling nitrogen through the solution for 2 min and is then charged with Pd(PPh3)4 (10 mg, 5 mol percent). After addition, the reaction mixture is stirred at 100°C for 16 h. The reaction mixture is cooled to rt and then diluted with ether (10 mL) and water (5 mL). The organic layer is separated and the aqueous layer is extracted with ether (2 x 5 mL). The combined organic layers are dried over anhydrous MgSO4 and the solvents are removed in vacuo. Purification by PTLC gives the corresponding arylation product; .EXAMPLE 14. SYNTHESIS OF tert-BUTYL-4-[6-(4-CHLOROPHENYL)-5-(3-FLUOROPYRIDIN-4-YL)- PYRAZIN-2-YL]-PlPERAZINE-l-CARBOXYLATE; This compound is prepared as described in Example 13, using <strong>[458532-97-3]3-fluoropyridine-4-boronic acid</strong>, and is obtained as a pale yellow solid; IH NMR (CDCl3, 300 MHz): delta 8.47 (IH, d, J = 5 Hz), 8.35(IH, d, J = 2 Hz), 8.20 (IH, s), 7.66 (IH, m), 7.50 (2H, m), 7.34 (IH, d, J = 8 Hz), 7.28 (IH, d, J = 8 Hz), 3.75 (4H, m), 3.61 (4H, m), 1.50 (9H, s). LC-MS: m/z for C24H25ClFN5O2 expected 469.2 (35Cl),471.2 (37Cl); found 470.3 (MH+), 472.3 (MH+).

Reference： [1]Patent: WO2006/113704,2006,A2 .Location in patent: Page/Page column 68

6
[ 881678-18-8 ]
[ 458532-97-3 ]
[ 928325-11-5 ]

Yield	Reaction Conditions	Operation in experiment
27%	With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 80℃; for 3.0h;	Reference Example 170 tert-butyl[5-(3-fluoropyridin-4-yl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]methyl}methylcarbamate; tert-Butyl[5-bromo-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]methyl}methylcarbamate (215 mg), <strong>[458532-97-3](3-fluoropyridin-4-yl)boronic acid</strong> hydrate (120 mg), sodium hydrogencarbonate (126 mg) and tetrakis(triphenylphosphine)palladium (87 mg) were added to a degassed mixture of 1,2-dimethoxyethane (8 mL) and water (2 mL), and the mixture was stirred under a nitrogen atmosphere at 80° C. for 3 hr. The reaction mixture was allowed to cool, a saturated aqueous sodium hydrogencarbonate solution was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (eluent: hexane-ethyl acetate=1:1) to give the title compound as a pale-yellow oil (yield 60 mg, 27percent). 1H-NMR (CDCl3) delta: 1.47 (9H, s), 2.61 (3H, s), 4.24 (2H, s), 6.35 (1H, s), 7.22-7.26 (1H, m), 7.35-7.40 (2H, m), 7.71-7.75 (1H, m), 8.47 (1H, d, J=4.8 Hz), 8.50 (1H, d, J=1.3 Hz), 8.70 (1H, d, J=2.1 Hz), 8.81 (1H, dd, J=4.8, 1.6 Hz).
	With tetrakis(triphenylphosphine) palladium(0); sodium hydrogencarbonate; In 1,2-dimethoxyethane; water; at 80℃; for 6.0h;	A degassed mixture of compound 19h (215 mg, 0.50 mmol),<strong>[458532-97-3](3-fluoropyridin-4-yl)boronic acid</strong> (120 mg, 0.76 mmol), tetrakis(triphenylphosphine)palladium (87 mg, 0.075 mmol) and NaHCO3(126 mg, 1.50 mmol) in DME (8 mL) and water (2 mL) was stirredat 80 C for 6 h. After cooling to room temperature, the reactionmixture was diluted with a solution of NaHCO3, and extracted withEtOAc. The extract was washed with brine, dried over anhydrousMgSO4, and concentrated under reduced pressure. The residuewas purified by basic silica gel column chromatography (n-hexane/EtOAc = 1/1), and then the obtained a pale yellow oil (60 mg)was dissolved in MeOH (5 mL). 4 mol/L HCl/EtOAc (1.5 mL) wasadded to the solution, and the mixture was stirred at 70 C for30 min, and then concentrated in vacuo. A solution of NaHCO3was added to the residue and the mixture was extracted withEtOAc. The extract was washed with brine, dried over anhydrousMgSO4, and concentrated under reduced pressure. The residuewas dissolved in EtOAc (5 mL), and a solution of fumaric acid(19 mg, 0.164 mmol) in MeOH (1 mL) was added to the solution.The resulting crystals were collected by filtration and rinsed withEtOAc to obtain 26f (45 mg, 19percent) as colorless crystals: mpH. Nishida et al. / Bioorganic & Medicinal Chemistry 25 (2017) 3298?3314 3311201 C; 1H NMR (DMSO-d6) d 2.37 (3H, s), 3.78 (2H, s), 6.49 (2H, s),6.64 (1H, d, J = 1.5 Hz), 7.30?7.33 (1H, m), 7.62?7.66 (1H, m), 7.77(1H, d, J = 1.5 Hz), 7.94?7.98 (1H, m), 8.49?8.51 (1H, m), 8.64 (1H,d, J = 1.5 Hz), 8.69 (1H, d, J = 2.3 Hz), 8.90 (1H, dd, J = 4.9 Hz,1.5 Hz), 3H not detected. Anal. Calcd for C20H19FN4O6S: C, 51.94;H, 4.14; N, 12.12. Found: C, 51.73; H, 4.13; N, 12.15.

Reference： [1]Patent: US2007/60623,2007,A1 .Location in patent: Page/Page column 48
[2]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 3298 - 3314

7
C₁₇H₁₉BrN₄O [ No CAS ]
[ 458532-97-3 ]
C₂₂H₂₂FN₅O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,2-dimethoxyethane; water; at 120℃; for 0.2h;Microwave irradiation;	A solution of compound 112 (150 mg; 0.4 mmol), 3-fluoro-4-pyridineboronic acid (169 mg; 1.2 mmol), [1,1'-bis(diphenylphosphino) ferrocene]dichloropalladium(II) (82 mg; 0.1 mmol) and Na2CO3 (254 mg; 2.4 mmol) in 2 mL DME/water (4:1) was placed in a microwave vial, degassed and heated to 120 0C for 12 minutes in an EMRY microwave apparatus. The reaction mixture was cooled to room temperature, then partitioned between ethyl acetate (20 mL) and 10 mL of water (10 mL). The organic layer was separated, dried and concentrated in vacuo and the resulting residue was purified using flash chromatography to provide Compound 113A. MH+ 392

Reference： [1]Patent: US2007/167435,2007,A1 .Location in patent: Page/Page column 62

8
[ 458532-97-3 ]
[ 216661-83-5 ]
C₁₈H₁₃FN₄O [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 4388 - 4392

9
[ 1210419-58-1 ]
[ 458532-97-3 ]
C₃₀H₂₄F₂N₆O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine;tetrakis(triphenylphosphine) palladium(0); In ethanol; toluene; at 120℃; for 0.333333h;microwave irradiation;	A solution of 3-amino-6-bromo-N-(4-((1R,3S)-3-(1,3-dioxoisoindolin-2-yl)cyclohexyl)pyridin-3-yl)-5-fluoropicolinamide (1.0 equiv), 3-fluoropyridin-4-yl-boronic acid (3.0 equiv.), tetrakistriphenylphosphine (0.2 equiv.) and triethylamine (3.0 equiv.) in 1:1 EtOH/toluene (0.1 M) was heated at 120° C. with microwave irradiation for 1200 seconds. Upon cooling, removal of the volatiles in vacuo, the Suzuki product was directly purified by reverse phase HPLC. The product fraction was lyophilized and the resulting phthalimide group was deprotected as described in Method 9 yielding, after RP HPLC purification and lyophilization, 5-amino-N-(4-((1R,3S)-3-aminocyclohexyl)-pyridin-3-yl)-3,3'-difluoro-2,4'-bipyridine-6-carboxamide as the TFA salt. LCMS (m/z): 425.1 (MH+); LC Rt=2.08 min.

Reference： [1]Patent: US2010/56576,2010,A1 .Location in patent: Page/Page column 87

10
[ 1221403-74-2 ]
[ 458532-97-3 ]
[ 1221403-66-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 1758 - 1762

11
[ 1221403-80-0 ]
[ 458532-97-3 ]
[ 1221403-54-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 1758 - 1762

12
[ 281225-12-5 ]
[ 458532-97-3 ]
[ 1257425-67-4 ]

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 8421 - 8439

13
[ 1279106-50-1 ]
[ 458532-97-3 ]
[ 1279106-51-2 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; toluene; at 100℃; for 18.0h;Inert atmosphere;	To a solution of 5-(5-Methyl-2-pyridin-2-yl-thiazol-4-yl)-2-trifluoromethanesulfonyloxy-indole-1-carboxylic acid ethyl ester (70 mg, 0.137 mmol) and <strong>[458532-97-3]3-fluoropyridine-4-boronic acid</strong> (21 mg, 0.150 mmol) in toluene (1.5 mL) and EtOH (1 mL) was added sat. NaHCO3 (0.67 mL).This mixture was purged with nitrogen (20 min) and then Pd(PPh3)4 (10 mol percent, 16 mg) was added.After stirring at 100° C. for 18 h, the mixture was filtered through Celite, and EtOAc (60 mL) was added.The organic phase was washed with brine, dried over Na2SO4, concentrated, and the crude material purified by column chromatography (33-66percent EtOAc-Hexane) to give 2-(3-Fluoro-pyridin-4-yl)-5-(5-methyl-2-pyridin-2-yl-thiazol-4-yl)-indole-1-carboxylic acid ethyl ester (8 mg).

Reference： [1]Patent: US2011/71150,2011,A1 .Location in patent: Page/Page column 51-52

14
[ 1279106-50-1 ]
[ 458532-97-3 ]
[ 1279103-49-9 ]

Reference： [1]Patent: US2011/71150,2011,A1

15
[ 1147077-78-8 ]
[ 458532-97-3 ]
2-amino-8-((3-fluoropyridin-4-yl)methyl)-4-phenyl-5H-indeno-[1,2-d]pyrimidin-5-one di-hydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 1402 - 1417

16
[ 1257055-94-9 ]
[ 458532-97-3 ]
[ 1376449-85-2 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,2-dimethoxyethane; water; at 100℃; for 16.0h;Sealed tube; Inert atmosphere;	In a sealed tube under argon atmosphere, to a solution of 2-(6-bromopyridin- 2-yl)-quinazoline (150 mg, 0.52 mmol) in dimethoxyethane (8 ml) 3-fluoro-4-pridine boronic acid is added followed by a 3M aq solution of sodium carbonate (0.7 ml). The mixture is degassed for 5 min, then (diphenylphosphinoferrocenyl)palladium dichloride, dicloromethane complex (43 mg, 0.05 mmol) is added. The tube is sealed and the mixture is stirred at 100°C for 16 hours. Subsequently, the mixture is cooled and poured into water, then extracted with ethyl acetate and washed with 2M solution of sodium hydroxyde. The collected organic fractions were washed with a 10percent sol of ammonia, with brine, dried over anhydrous sodium sulphate, filtered and evaporated to dryness. The remainder is purified by flash chromatography on silica gel, using a gradient of cyclohexane / ethyl acetate 100 : 1 to 1 : 100 as eluent to obtain 2-(3'- fluoro-[2,4']bipyridinyl-6-yl)-quinazoline (Compound Tl .1.176). 1H- MR (CDC13): delta = 7.72 (t, 1H), 7.94 - 8.08 (m, 4H), 8.20 - 8.30 (m, 2H), 8.55-8.62 (m, 2H), 8.74 (dd, 1H), 9.62 (s, 1H) MS: m/z = 303 (M+l). according to the same procedure, starting from 2-(6-bromo-5-methylpyridin-2-yl)- quinazoline (150 mg, 0.52 mmol) and 2-methoxy- 5 -pyridine boronic acid after purification 2-(6'-methoxy-3-methyl-[2,3']bipyridinyl-6-yl)-quinazoline was obtained (Compound Tl .1.137). 1H- MR (CDC13): delta = 2.50 (s, 3H), 4.02 (s, 3H), 6.89 (d, 1H), 7.65 (t, 1H), 7.80 (d, 1H), 7.91 - 8.02 (m, 3H), 8.20 (d, 1H), 8.47 (d, 1H), 8.55 (d, 1H), 9.61 (s, 1H) MS: m/z = 329 (M+l).

Reference： [1]Patent: WO2012/69601,2012,A1 .Location in patent: Page/Page column 56-57

17
[ 1438887-25-2 ]
[ 458532-97-3 ]
[ 1438881-78-7 ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; at 150℃; for 0.25h;Microwave irradiation;	Synthesis of N* 1 *-[2-(3-fluoro-pyridin-4-yl)-5,6,7,8-tetrahydro-benzo[4,5]thieno[2,3- d]pyrimidin-4-yl] -ethane- 1 ,2-diamine [97]A microwave vial was charged with [2-(2-chloro-5,6,7,8-tetrahydro- benzo[4,5]thieno[2,3-d]pyrimidin-4-ylamino)-ethyl]-carbamic acid tert-butyl ester [AA- 49] (80mg, 0.210 mmol), <strong>[458532-97-3]3-fluoropyridine-4-boronic acid</strong> hydrate (38mg, 0.24 mmol), tetrakis (triphenyl phosphine) palladium (12 mg, 0.01 mmol), Na2CC"3 (2M in water, 300mu1, 0.6 mmol) and EtOH (1ml). The reaction was heated to 150°C for 15 minutes under microwave irradiation. The mixture was then filtered through a plug of silica, washed with methanol and the filtrate was concentrated under reduced pressure. To a solution of the crude product in DCM (2 ml) was added TFA (2 ml) and the mixture was stirred at room temperature for 1 hour. After completion the mixture was loaded onto a SCX-2 cartridge and washed with methanol. The product was released from the cartridge using a solution of 2M ammonia / methanol. The ammonia / methanol eluent was concentrated under reduced pressure and the crude product was purified by preparative HPLC (method A) to yield to the title compound. LCMS method: 2, RT: 2.41 min, MI: 344 [M+l].

Reference： [1]Patent: WO2013/78126,2013,A1 .Location in patent: Page/Page column 207-208

18
[ 1443253-24-4 ]
[ 458532-97-3 ]
[ 1443253-17-5 ]

Yield	Reaction Conditions	Operation in experiment
31.2%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; at 100℃; for 0.333333h;Microwave irradiation;	General procedure: 5-Bromo-1-octyl-1H-indole (20) and (5-bromo-1-octyl-1H-indol-3-ylmethyl)ethylamine (21) were prepared as previously described [10]. To a suspension of 21 (0.8 mmol), the substituted phenyl, pyridine or pyrimidine boronic acid (1.25 mmol) and tetrakis(triphenylphosphine) palladium(0) (0.05 mmol) in dry 1,4-dioxane (3 mL) in a microwave reaction tube (20 mL) was added K2CO3 solution (2 mL, 1.5 mM) and subjected to microwave heating (20 min, 100 °C) with stirring. The resulting dark colored solution was extracted with ethyl acetate (25 mL x 2), the combined organic layers were washed consecutively with water and brine, and dried (anhydrous Na2SO4). The organic solvent was removed in vacuo and the residue purified by column chromatography with CHCl3-methanol as eluting solvents.

Reference： [1]European Journal of Medicinal Chemistry,2013,vol. 63,p. 378 - 386

19
[ 1494218-39-1 ]
[ 458532-97-3 ]
[ 1494218-42-6 ]

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 9586 - 9600

20
[ 1586045-04-6 ]
[ 458532-97-3 ]
[ 1586040-76-7 ]

Yield	Reaction Conditions	Operation in experiment
		Example 240 N-(5-((2S,5R,6S)-5-amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-2-(3-fluoropyridin-4-yl)thiazole-4-carboxamide 240 Following the procedure for Example 101 starting from tert-butyl ((3S,4R,7S)-7-(4-(2-bromothiazole-4-carboxamido)-1-methyl-1H-pyrazol-5-yl)-3-fluorooxepan-4-yl)carbamate (Intermediate 99), and replacing 3,6-dihydro-2H-pyran-4-boronic acid pinacol ester with <strong>[458532-97-3](3-fluoropyridin-4-yl)boronic acid</strong> gave 240. 1H NMR (400 MHz, DMSO-d6) delta 10.09 (s, 1H), 8.87 (d, J=2.4 Hz, 1H), 8.73-8.64 (m, 2H), 8.23 (dd, J=6.4, 5.0 Hz, 1H), 7.78 (s, 1H), 5.04-4.77 (m, 2H), 4.25-4.09 (m, 1H), 4.06-3.92 (m, 1H), 3.78 (s, 3H), 3.27-3.20 (m, 1H), 2.19-2.08 (m, 1H), 1.91-1.76 (m, 3H), 1.69-1.59 (m, 1H). LCMS (ES+) m/z 435 (M+1).

Reference： [1]Patent: US2014/88117,2014,A1 .Location in patent: Page/Page column

21
[ 458532-97-3 ]
[ 1586040-76-7 ]

Reference： [1]Patent: US2014/88117,2014,A1

22
[ 458532-97-3 ]
[ 1521192-57-3 ]

Yield	Reaction Conditions	Operation in experiment
		Intermediate 113 2-(3-fluoropyridin-4-yl)thiazole-4-carboxylic acid Following the procedure of Intermediate 104, replacing 2,6-difluoro-4-methoxyphenylboronic acid with <strong>[458532-97-3](3-fluoropyridin-4-yl)boronic acid</strong> gave the title compound.

Reference： [1]Patent: US2014/88117,2014,A1 .Location in patent: Page/Page column

23
[ 458532-97-3 ]
[ 22282-73-1 ]

Yield	Reaction Conditions	Operation in experiment
75%	With copper(ll) sulfate pentahydrate; ellagic acid; In methanol; at 60℃; under 760.051 Torr; for 8h;Green chemistry;	General procedure: In a typical reaction, 10 mol% CuSO4·5H2O, (0.049 g, 0.2 mmol)and 6.7 mol% EA (20 mg) were mixed in methanol followed by2 mmol of phenylboronic acid. This reaction mixture was kept ina preheated oil bath by maintaining the temperature at 60 C andstirred under atmospheric pressure. After completion of the reac-tion, modified by TLC, the mixture was washed twice with hot ethylacetate to remove the reactant and product. The hot ethyl acetatewas removed from the reaction mixture and the resulting crudeproduct was purified by a column chromatography using silicagel 260 mesh (pet ether:ethyl acetate) ratio (25:75). The recov-ered catalyst was reused for the next run. All the products werecharacterized by1H and13C NMR spectra.

Reference： [1]Journal of Molecular Catalysis A: Chemical,2014,vol. 395,p. 500 - 505

24
[ 46064-79-3 ]
[ 458532-97-3 ]
methyl 3-amino-4-(3-fluoropyridin-4-yl)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 50 - 80℃; for 8.0h;Inert atmosphere;	Methyl 3-amino-4-bromobenzoate (4 g, 17.39 mmol), (3-fluoropyridin-4- yl)boronic acid (5.5 g, 39.0 mmol), dioxane (10 mL), water (2 mL) and potassium carbonate (8.41 g, 60.9 mmol) were taken in a dried two neck RB (25mL) and purged with nitrogen for 10 minutes. To this mixture was added PdCi2(dppf) (1.27 g, 1.74 mmol) at 50 °C. The mixture was flushed with nitrogen and heated at 80 °C for 8 h. The reaction mixture was cooled to room temperature, then was diluted with the DCM. The organic phase was washed with the water, dried over sodium sulphate. The crude compound was purified by silica gel chromatography (ethyl acetate/petroleum ether, (30-65percent) to afford 2.9 g (68percent) of the title compound. LC-MS (ESI) m/z: 241.0 [M+H]+; XH NMR (400 MHz, chloroform-d) delta ppm 8.60 (d, J=1.57 Hz, 1 H) 8.52 (dd, J=4.86, 1.10 Hz, 1H) 7.48 - 7.52 (m, 2 H) 7.35 - 7.39 (m, 1H) 7.19 (d, J=7.78 Hz, 1H) 3.93 (s, 3 H) 3.79 - 3.84 (m, 2 H).

Reference： [1]Patent: WO2015/2926,2015,A1 .Location in patent: Page/Page column 103

25
[ 458532-97-3 ]
3-(3-methoxyphenyl)-N-(9H-pyrido[3,4-b]indol-7-yl)propanamide [ No CAS ]

Reference： [1]Patent: WO2015/2926,2015,A1

26
[ 458532-97-3 ]
9H-pyrido[3,4-b]indole-7-carboxylic acid [ No CAS ]

Reference： [1]Patent: WO2015/2926,2015,A1

27
[ 458532-97-3 ]
2-(trimethylsilyl)ethyl 9H-pyrido[3,4-b]indol-7-ylcarbamate [ No CAS ]

Reference： [1]Patent: WO2015/2926,2015,A1

28
[ 458532-97-3 ]
9H-pyrido[3,4-b]indol-7-amine [ No CAS ]

Reference： [1]Patent: WO2015/2926,2015,A1

29
N-(3-bromo-5-(5-(1-methyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-1-yl)-phenyl)acetamide [ No CAS ]
[ 458532-97-3 ]
N-(3-(3-fluoropyridin-4-yl)-5-(5-(1-methyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-1-yl)phenyl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
21%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,2-dimethoxyethane; water; at 90℃; for 2.0h;Inert atmosphere;	d) A solution of the compound of Example 277(c) (0.1 g, 0.243 mmol) in 1,2-dimethoxyethane (4 ml) was degassed by N2 bubbling for 5 min. (3-Fluoropyridin-4-yl)-boronic acid (0.041 g, 0.292 mmol, 1.2 eq.) was added and the mixture was degassed for another 5 min. Pd(dppf)Cl2 (0.020 g, 0.024 mmol, 0.1 eq.) and aqueous sodium carbonate (0.077 g, 0.731 mmol, 3.0 eq.) were added and the procedure of Example 1(d) was followed. The crude residue of the product was purified by preparative HPLC to give the product in 21percent yield. 1H NMR (300 MHz, DMSO-d6): delta 10.5 (s, 1H), 8.97 (s, 1H), 8.75 (s, 1H), 8.59 (d, 1H), 8.24 (s, 1H), 8.20 (s, 1H), 8.01 (s, 1H), 7.97 (d, 2H), 7.80-7.65 (m, 4H), 3.89 (s, 3H), 2.13 (s, 3H); LC-MS (ESI): Calculated mass: 426.16; Observed mass: 427.1 [M+H]+ (rt: 0.20 min).

Reference： [1]Patent: US2015/11548,2015,A1 .Location in patent: Paragraph 0654

30
[ 1023620-72-5 ]
[ 458532-97-3 ]
7-tert-butoxycarbonylamino-4-(3-fluoro-4-pyridyl)-5,7,8,9-tetrahydrobenzocyclohepten-6-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In 1,2-dimethoxyethane;Inert atmosphere;	General procedure: General procedure (a): a mixture of bromoacetamide 2a or 10a, arylboronic acid (1.5 equiv), CsF (2.2 equiv) and Pd(PPh3)4 or PEPPSI-iPr (0.1?0.15 equiv) in dry 1,2-dimethoxyethane (DME, 3 mL) was stirred under Ar at 85 °C for 16 h. The reaction mixture was diluted with AcOEt, washed with brine and dried over MgSO4. The solvent was evaporated and the residue purified by flash chromatography (cyclohexane/AcOEt). General procedure (b): same procedure with K2CO3 (1.5 equiv) as base and in DME and H2O as reaction solvent 5/1. General procedure (c): same procedure with K2CO3 (3 equiv) as base and in DME and H2O as reaction solvent 4/1. The reaction mixture was then heated at 125 °C under microwave irradiation for 30 min. General procedure (d): same procedure with K2CO3 (4 equiv) as base, and in DME and H2O as reaction solvent 4/1. The reaction mixture was then heated at 125 °C under microwave irradiation for 30 min. 6.4.1.27 7-tert-Butoxycarbonylamino-4-(3-fluoro-4-pyridyl)-5,7,8,9-tetrahydrobenzocyclohepten-6-one (33a) Mixture 65/35 of two rotamers M and m. Colorless solid. Mp 184-185 °C. IR (KBr): 3437, 1724, 1671, 1548, 1412, 1281, 1164, 796 cm-1. 1H NMR (CDCl3, 400 MHz): 8.55 (s, 1H, H-2', M+m); 8.51 (m, 1H, H-6', M+m); 7.43 (m, 1H, H-5', M+m); 7.32 (m, 2H, H-2 and H-3, M+m); 7.19 (m, 1H, H-1, M+m); 5.42 (br s, 1H, NH, M); 5.36 (br s, 1H, NH, m); 4.59 (m, 1H, H-7, M); 4.44 (m, 1H, H-7, m); 3.78 (d, 1H, Ha-5, M); 3.69 (d, 1H, Ha-5, m); 3.59 (d, 1H, Hb-5, m); 3.49 (d, 1H, Hb-5, M); 3.13 (m, 2H, CH2-9, m); 3.00 (m, 2H, CH2-9, M); 2.73 (m, 1H, Ha-8, M); 2.63 (m, 1H, Ha-8, m); 1.54 (m, 1H, Hb-8, M+m); 1.44 (s, 9H, tBu, M+m). J(5a,5b) = 15.6 Hz. 13C NMR (CDCl3, 100 MHz): 204.7 (C(6)); 158.1 (NCO2); 155.45 (C(3')); 155.34 (C(9a)); 146.3 (C(6')); 141.8 (C(4)); 140.7 (C(4')); 139.0 (C(2')); 131.3 (C(4a)); 130.6 (C(2)); 129.6 (C(1)); 128.2 (C(3)); 126.9 (C(5')); 80.3 (CMe3); 61.2 (C(7)); 44.1 (C(5)); 34.8 (C(8)); 31.8 (C(9)); 28.8 (CMe3). 19F NMR (CDCl3, 282 MHz): -128.52 (s, m); -129.79 (s, M). HR-MS (ESI-QTof) calcd for C21H24FN2O3 [M+H]+: 371.1766; found: 371.1772.

Reference： [1]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 3192 - 3207

31
hexanoic acid [1-acetyl-4-(4-bromophenyl)-4-methyl-1,2,3,4-tetrahydroquinolin-6-yl]amide [ No CAS ]
[ 458532-97-3 ]
hexanoic acid {1-acetyl-4-[4-(3-fluoropyridin-4-yl)phenyl]-4-methyl-1,2,3,4-tetrahydroquinolin-6-yl}amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
19%	With bis-triphenylphosphine-palladium(II) chloride; potassium phosphate tribasic heptahydrate; triphenyl-arsane; In 1,4-dioxane; water; for 5.0h;Inert atmosphere; Reflux;	Example 14Hexanoic acid { 1 -acetyl-4-[4-(3-fluoro-pyridin-4- yl)-phenyl]-4-methyl-1 ,2,3,4-tetrahydro-quinolin-6-yl}-amideA stirred solution of the compound described in Example 9 (50 mg, 0.11 mmol), <strong>[458532-97-3]3-fluoropyridine-4-boronic acid</strong> (42 mg, 0.30 mmol), potassium phosphate tribasic heptahydrate (44 mg, 0.13 mmol), bis(triphenylphosphine)palladium(II) chloride (4.6 mg, 6.6 tmol), triphenylarsine (2.3 mg, 7.6 tmol) and H20 (0.5 ml) in dioxane (3 ml), under N2 atmosphere,was heated to reflux for 5 hours. The reaction mixture was then cooled to ambient temperature, quenched with aqueous NaHCO3 and diluted with EtOAc. The organic layer was washed with H20 and brine, dried (Na2SO4) and concentrated under reduced pressure. The crude product was purifiedby column chromatography on silica, followed by preparative HPLC. Freeze-drying afforded the title compound (10 mg, 19percent). Data: (mlz)=474.5 (M+H).

Reference： [1]Patent: US9174940,2015,B2 .Location in patent: Page/Page column 29; 30

32
[ 57135-09-8 ]
[ 458532-97-3 ]
2-((3-fluoropyridin-4-yl)thio)thiazolo[5,4-b]pyridine [ No CAS ]

Reference： [1]European Journal of Organic Chemistry,2016,vol. 2016,p. 1963 - 1967

33
4-[1-[2-methylsulfanyl-6-(3-pyridyl)pyrimidin-4-yl]-4-piperidyl]morpholine [ No CAS ]
[ 458532-97-3 ]
4-(1-(2-(3-fluoropyridin-4-yl)-6-(pyridin-3-yl)pyrimidin-4-yl)piperidin-4-yl)morpholine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 6101 - 6120

34
(1S,8R)-12-bromo-15-oxatetracyclo[6.6.1.0^2,7.0^9,14]pentadeca-2,4,6,9,11,13-hexaene-4-carboxylic acid [ No CAS ]
[ 458532-97-3 ]
(1R,8S)-12-(3-fluoropyridin-4-yl)-15-oxatetracyclo-[6.6.1.0^2,7.0^9,14]pentadeca-2,4,6,9,11,13-hexaene-4-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 80℃; for 3.0h;	Step 5: Into a 50-mL round-bottom flask, was placed a mixture of (1 S,8R)-12-bromo-1 5-oxatetracyclo [6.6.1.027, ue? 14j pentadeca-2,4,6,9, 11,1 3-hexaene-4-carboxylic acid (INT4a1;158.0 mg, 0.50 mmol, 1.00 equiv), dioxane (8.0 mL), 1120 (0.8 mL), (3-fluoropyridin-4- vl)boronic acid (212 mg, 1.50 mmol, 3.00 equiv), Pd(PPh3)4 (18.3 mg, 0.02 mmol, 0.05 equiv) and sodium carbonate (159.0 mg, 1.50 mmol, 3.00 equiv). The resulting mixture was stirred for 3 h at 80 °C then it was cooled to RT and concentrated. The crude product waspurified by silica gel column chromatography eluting with DCM/MeOH (5/1) to afford 140.0 mg (84percent) of (1 R,8S)- 12-(3-fluoropyridin-4-yl)- 1 5-oxatetracyclo[6. 6.1. 02?7.09?4jpentadeca- 2,4,6,9,1 1,13-hexaene-4-carboxylic acid as an off-white solid.

Reference： [1]Patent: WO2016/201052,2016,A1 .Location in patent: Page/Page column 321

35
[ 458532-97-3 ]
4-[(1R,8S)-12-carboxy-15-oxatetracyclo-[6.6.1.0^2,7.0^9,14]pentadeca-2,4,6,9,11,13-hexaene-4-yl]-3-fluoropyridin-1-ium-1-olate [ No CAS ]

Reference： [1]Patent: WO2016/201052,2016,A1

36
[ 458532-97-3 ]
4-[(1R,8S)-12-[(6-amino-4-cyclopropyl-2-methylpyridin-3-yl)methyl]-carbamoyl}-15-oxatetracyclo-[6.6.1.0^2,7.0^9,14]pentadeca-2,4,6,9,11,13-hexaene-4-yl]-3-fluoropyridin-1-ium-1-olate [ No CAS ]

Reference： [1]Patent: WO2016/201052,2016,A1

37
[ 881678-18-8 ]
[ 458532-97-3 ]
1-[5-(3-fluoropyridin-4-yl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine fumarate [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 3298 - 3314

38
[ 1400689-72-6 ]
[ 458532-97-3 ]
[ 1400686-82-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 3101 - 3106

39
C₁₀H₆BrN₃ [ No CAS ]
[ 458532-97-3 ]
ACI-2698 [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
24%	With tetrakis(triphenylphosphine) palladium(0); cesium fluoride; In methanol; 1,2-dimethoxyethane; at 150℃; under 9000.9 Torr; for 0.5h;Microwave irradiation; Sealed tube; Inert atmosphere;	In a 5 mL microwave tube was added the title compound from Preparative Example A (0.05 g, 0.202 mmol) and <strong>[458532-97-3](3-fluoropyridin-4-yl)boronic acid</strong> (0.0398 g, 0.282 mmol) in dimethoxyethane (Ratio: 2, Volume: 1.344 mL) and methanol (Ratio: 1 , Volume: 0.672 mL). Cesium fluoride (0.0306 g, 0.202 mmol) was added and the resulting suspension was degassed for 5 minutes with argon. Then, tetrakis(triphenylphosphine)palladium(0) (0.0419 g, 0.036 mmol) was added, the tube was sealed and the reaction mixture was heated at 150°C in Biotage Initiator microwave for 30 minutes (p = 12 bar). The reaction mixture was diluted with ethyl acetate and washed with water and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The residue was purified by chromatography on silica (10 g HP-SIL) using a Biotage Isolera system employing a dichloromethane/methanol gradient (100/0 -> 80/20) to afford the title compound F-3b as a light brown solid (0.013 g, 24 percent). (0207) 1H-NMR (400 MHz, DMSO-d6) delta = 9.46 (s, 1 H), 8.82 (d, 1 H), 8.77 (d, 1 H), 8.63 (d, 1 H), 8.56 (d, 1H), 8.09 (dd, 1 H), 7.91 (dd, 1 H), 7.54 (d, 1 H) (0208) MS (ESI); m/z = 265.16 [M+H]+

Reference： [1]Patent: WO2018/15549,2018,A1 .Location in patent: Page/Page column 33; 34

40
(S)-7-bromo-8-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-5,6-dihydronaphthalen-2-ol [ No CAS ]
[ 458532-97-3 ]
8-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-7-(3-fluoro-4-pyridyl)-5,6-dihydronaphthalen-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
36%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 70℃; for 2.0h;	To a solution of 7-bromo-8-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-5,6- dihydronaphthalen-2-ol (Intermediate Ig1 , 150 mg, 336.06 muetaetaomicronIota) in dioxane (1 .6 ml), was added 3-fluoropyridin-4-yl boronic acid (52.09 mg, 369.66 muetaiotaomicronIota), Cs2C03 (0.8 ml of a 1 .5 N aqueous solution, 1.20 mmol), and Pd(dppf)CI2 (12.94 mg, 16.80 muetaiotaomicronIota). The reaction mixture was heated at 70°C for 2 hours. Water was added, and the reaction mixture was extracted with EtOAc. The organic phase was dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography eluting with a gradient of diisopropyl ether and MeOH (95/5 and 90/10; V:V) to give 56 mg (36percent) of 8-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-7-(3- fluoro-4-pyridyl)-5,6-dihydronaphthalen-2-ol.

Reference： [1]Patent: WO2018/91153,2018,A1 .Location in patent: Page/Page column 228

41
[ 2178-24-7 ]
[ 458532-97-3 ]
C₁₅H₁₄FNO₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 138 - 142

42
[ 458532-97-3 ]
C₁₃H₁₀FNO₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 138 - 142

43
[ 458532-97-3 ]
C₁₃H₁₁FN₂O [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 138 - 142

44
(S)-tert-butyl (1-(6-bromo-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl)ethyl)carbamate [ No CAS ]
[ 458532-97-3 ]
(S)-tert-butyl (1-(6-(3-fluoropyridin-4-yl)-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl)ethyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
9%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 90℃; for 1.0h;Microwave irradiation;	A suspension of compound 19 (100 mg, 0.27 mmol), 3-Fluoropyridine-4-boronic acid (75 mg, 0.53 mmol), PdCl2(dppf) (20 mg, 0.03 mmol), Cs2C03 (261 mg, 0.80 mmol) in 1,4- dioxane (4 mL) and H20 (1 mL) was microwaved at 90 °C for lh, LC-MS showed that the start materials was consumed up, the reaction was repeated once at the same scale, same amount, the combined two batches were poured into a mixture of DCM (60 mL) and H20 (50 mL), the organic layer was separated and washed with brine, dried over anhydrous Na2S04, concentrated in vacuo, the residue was purified by column (EtOAc/Hex 1/5 to 1/1) to give compound 20 (20 mg, 9percent yield) as a light yellow solid. MS (ESI) (M/Z): [M+H]+ =391.1; 1H NMR (400 MHz, CDC13) delta 11.09 (s, 1H), 8.66 (d, = 2.5 Hz, 1H), 8.55 (d, = 5.0 Hz, 1H), 7.89 (s, 1H), 7.66 - 7.60 (m, 1H), 4.81 (s, 1H), 1.64 (s, 3H), 1.47 (d, = 11.3 Hz, 9H).

Reference： [1]Patent: WO2018/217439,2018,A1 .Location in patent: Page/Page column 29; 32

45
(R)-4-bromo-N-(1-(3-methoxyphenyl)ethyl)benzamide [ No CAS ]
[ 458532-97-3 ]
[ 1127308-67-1 ]

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

46
C₁₈H₂₁ClIN₃O₂Si [ No CAS ]
[ 458532-97-3 ]
C₂₃H₂₄ClFN₄O₂Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,2-dimethoxyethane; water; for 1.0h;Reflux;	General procedure: S2 (1.0 g, 2 mmol), phenylboronic acid (0.24 g, 2 mmol),Pd(dppf)Cl2 (0.293 g, 0.4 mmol), K2CO3 (0.552 g, 4 mmol), 20 mL1,2-dimethoxy-ethane, and 5mL ofwaterwere added to a flask. The reaction was stirred and heated to reflux for 1 h. After cooling, thesolution was concentrated under vacuum and the residue wasdiluted with brine and extracted with ethyl acetate three times. Thecombined organic layers were dried with anhydrous sodium sulfateand filtered. The solvent was removed under reduced pressure. Theresidue was purified by silica flash chromatography to yield S3(0.3 g, 33%).

Reference： [1]European Journal of Medicinal Chemistry,2019,vol. 173,p. 167 - 183

47
5-chloro-N-(2,2,2-trifluoroethyl)pyrazine-2-carboxamide [ No CAS ]
[ 458532-97-3 ]
5-(3-fluoropyridin-4-yl)-N-(2,2,2-trifluoroethyl)pyrazine-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44.5%	With di-tert-butyl[dichloro({di-tert-butyl[4-(dimethylamino)phenyl]phosphaniumyl})palladio][4-(dimethylamino)phenyl]phosphanium; potassium acetate; In water; acetonitrile; at 20 - 80℃; for 9.0h;Inert atmosphere;	The 5-chloro-N- (2,2,2-trifluoroethyl) pyrazine-2-carboxamide (2.98 g, 12.44 mmol) prepared in Synthesis Example 2-1 was dissolved in acetonitrile (30 mL) Then, <strong>[458532-97-3]3-fluoropyridine-4-boronic acid</strong> (2.98 g, 21.15 mmol) was added at room temperature under a nitrogen atmosphere.Then, an aqueous solution of potassium acetate (3.66 g, 37.3 mmol) dissolved in water (3 mL) is added, and then [4- (N, N-dimethylamino) phenyl] di-tert-butylphosphine dichloropalladium ( II) (0.88 g, 1.24 mmol) was added, and the mixture was heated and stirred at 80 ° C. for 9 hours.After completion of the reaction, water is added, and the mixture is extracted twice with ethyl acetate, and the extracted ethyl acetate layer is dried over anhydrous magnesium sulfate, filtered and then acetic acidEthyl was distilled off under reduced pressure with an evaporator.The resulting crude product is purified by silica gel chromatography to give 5- (3-fluoropyridin-4-yl) -N- (2,2,2-trifluoroethyl) pyrazine-2-carboxamide (1.66 g) , 44.5percent, yellow solid).

Reference： [1]Patent: JP2019/94290,2019,A .Location in patent: Paragraph 0253

48
4-((5-chloro-1-toluenesulfonyl-1H-benzo[d]imidazol-2-yl)methyl)cyclohex-1-en-1-yl trifluoromethanesulfonate [ No CAS ]
[ 458532-97-3 ]
5-chloro-2-((4-(3-fluoropyridin-4-yl)cyclohex-3-en-1-yl)methyl)-1H-benzo[d]imidazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
18%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 100℃; for 3.0h;Inert atmosphere;	4-((5-chloro-1-toluenesulfonyl-1H-benzo[d]imidazol-2-yl)methyl)cyclohex-1-en-1-yl trifluoromethanesulfonate 20d ( 800 mg, 1.46 mmol), <strong>[458532-97-3](3-fluoropyridin-4-yl)boronic acid</strong> (247 mg, 1.75 mmol),[1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (107 mg, 0.146 mmol), potassium carbonate (302 mg, 2.19 mmol), water (5 ml) and 1,4-dioxane (20 ml) were mixed, then heated to 100 C under a nitrogen atmosphere and stirring was continued for 3 hours. After cooling to room temperature, the solvent was removed under reduced pressure, the residue was purified by silica gel column chromatography (dichloromethane / methanol = 19/1), To give the target product 5-chloro-2-((4-(3-fluoropyridin-4-yl)cyclohex-3-en-1-yl)methyl)-1H-benzo[d]imidazole 22a (90mg, Yellow solid), Yield: 18%.

Reference： [1]Patent: CN109956927,2019,A .Location in patent: Paragraph 0270-0271

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[ 458532-97-3 ] Synthesis Path-Upstream 1~2

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Organoboron

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Pyridines

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