Name: 872041-86-6|(5-Fluoropyridin-3-yl)boronic acid|95%
Brand: Ambeed
SKU: A113732
Price: 5.0 USD
Availability: InStock
Rating: 96 (27 reviews)

1
[ 872041-86-6 ]
[ 1097633-59-4 ]
[ 1097633-60-7 ]

Yield	Reaction Conditions	Operation in experiment
27%	With potassium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,1-dimethoxyethylene; ethanol; water; at 130℃; for 0.25h;Microwave irradiation 2450 MHz;	-(3-bromophenyl)-l-[4-(methylsulfonyl)phenyl]-lH-isoindol-3-amine (88.3 mg, 0.2 mmol), <strong>[872041-86-6](5-fluoropyridin-3-yl)boronic acid</strong> (89.2 mg, 0.4 mmol), [1,1'- bis(diphenylphosphino)ferrocene]palladium(II) chloride dichloromethane adduct (16 mg, 0.02 mmol), potassium carbonate (83 mg, 0.6 mmol) in dimethoxyethene, water and ethanol 6:3:1 (3 mL) was irradiated under an argon atmosphere in a microwave at 130 0C for 15 min. When cooled to room temperature the mixture was filtered and dimethyl sulfoxide (1.0 mL) was added. The residue was concentrated in vacuo and purified by preparative etaPLC to give 24.5 mg (27 % yield) of the title compound. 1H NMR (400 MHz, DMSO-J6) delta ppm 8.65 (s, 1 H), 8.53 - 8.62 (m, 1 H), 7.88 - 7.99 (m, 2 H), 7.77 - 7.88 (m, 3 H), 7.56 - 7.72 (m, 4 H), 7.42 - 7.56 (m, 4 H), 6.88 (br s, 2 H), 3.16 (s, 3 H), acetate 1.91 (1.5 H); MS (AP) m/z 456 [M-I]+.

Reference： [1]Patent: WO2009/5470,2009,A1 .Location in patent: Page/Page column 36

2
[ 872041-86-6 ]
[ 1138159-32-6 ]
5-[2-chloro-9-(2-methoxy-1-methyl-ethyl)-9H-purin-6-yl]-3-fluoropyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 80℃; for 3h;	A solution of 9-sec-butyl-2,6-dichloro-9H-purine (0.312mmol), 3- fluoropyridine-5-boronic acid (0.312mmol) and 1 ,1'-bis(diphenylphosphino) ferrocene palladium (II) chloride, complexed with dichloromethane, (0.031 mmol) were taken up in a mixture of peroxide free dioxane (4ml) and a 2M aqueous solution of sodium carbonate (0.816mmol) was added. The reaction mixture was degassed and purged with nitrogen. This reaction mixture was then stirred on an oil bath maintained at 8O0C for 3h. Conversion was monitored by LC/MS for the disappearance of the starting purine.The reaction mixture was cooled to room temperature and the solvents removed under reduced pressure. The residue was taken up in ethyl acetate and water. The organic phase was separated and the aqueous layer further extracted with 3x100 ml portions of ethyl acetate. The organics were dried over sodium sulfate and the solvents removed under vacuum to give 5-[2- chloro-9-(2-methoxy-1 -methyl-ethyl)-9H-purin-6-yl]-pyridin-2-ylamine. This was taken up in dimethyl acetamide (5ml) and morpholine (O.deltammol) was added to the solution. The reaction mixture was then heated on an oil bath maintained at 940C for 12h. Conversion was monitored by LC-MS. The crude material was directly loaded onto a preparative HPLC column and purified by chromatography to give compound (134) (2.98mg). MS (m/z): 370.23 [MH]+.

Reference： [1]Patent: WO2009/45174,2009,A1 .Location in patent: Page/Page column 103

3
[ 407-20-5 ]
[ 872041-86-6 ]

Yield	Reaction Conditions	Operation in experiment
87.4%		To a 700 L low temperature reactor were added 3-bromo-5-fluoropyridine (2a) (25 Kg, 142 moles, 1.0 equiv.), THF (222.5 Kg) and isopropyl borate (28 Kg, 149.3 moles, 1.05 equiv.). The resulting mixture was cooled to -90 0C ~ -80 0C while stirred. Then n-BuLi (40.2 Kg, 2.5 M, 142 moles, 1.0 equiv.) was added dropwise (2Kg/h) maintaining the temperature below -87 0C. After the addition was complete, the mixture was maintained at -88 - 83 0C for 2.5 h. When the reaction was deemed complete by HPLC analysis, it was quenched by addition of 9 % aqueous HCl (7.7 Kg). The mixture was transferred to a 1000 L glass-lined reactor and the temperature returned to -20 ~ -10 0C. Additional HCl solution (122.3 Kg) was then added until pH was adjusted to 1-2 maintaining the temperature at 0-10 0C. The mixture was then held for 0.5 h in order to allow layers to separate. The organic <n="38"/>layer was separated and washed with saturated brine (38 Kg). It was stirred for 0.5 h and then held again for 0.5 h to allow layer separation. The aqueous layer was separated and the combined aqueous layers were extracted with EtOAc twice (51+25 Kg). The organic phase was separated and pH was adjusted to a value of 6 by using 30 % aqueous NaOH solution (27.4 Kg). At this pH a solid precipitated out. The slurry was filtered by centrifuge and allowed to dry in a tray dryer at 40-45 0C. Title compound 2b was obtained as a white solid (17.5 Kg, 87.4 %, purity: 98.6 % AUC using method B)

Reference： [1]Patent: WO2009/61875,2009,A2 .Location in patent: Page/Page column 36-37

4
[ 872041-86-6 ]
[ 1350178-74-3 ]
[ 1346803-68-6 ]

Yield	Reaction Conditions	Operation in experiment
14%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 90℃; for 16h;Inert atmosphere;	Example 53 3-(5-Difluoromethoxy-4,6-dimethyl-pyridin-2-yl)-7-fluoro-3-(5'-fluoro-[2,3']bipyridinyl-4-yl)-3H-isoindol-1-ylamine A mixture of 3-(2-chloro-pyridin-4-yl)-3-(5-difluoromethoxy-4,6-dimethyl-pyridin-2-yl)-7-fluoro-3H-isoindol-1-ylamine 1 (0.14 g, 0.32 mmol), <strong>[872041-86-6]5-fluoropyridine-3-boronic acid</strong> (0.068 g, 0.485 mmol), Pd(PPh3)4 (0.065 g, 0.056 mmol), aqueous Na2CO3 (2M, 1 mL, 2 mmol) in DME (4 mL) was degassed for 15 minutes using nitrogen and then heated in a sealed tube at 90 C. for 16 hours. The reaction mixture was cooled to room temperature, diluted with EtOAc (20 mL) and washed with saturated NaHCO3 solution (10 mL) and H2O (20 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC to afford the title compound (22 mg, 14%). 1H NMR (400 MHz, CDCl3) delta ppm 8.92 (br. s., 1H) 8.61 (d, 1H) 8.48 (br. s., 1H) 8.00 (d, 2H) 7.85 (s, 1H) 7.54-7.61 (m, 1H) 7.51 (s, 1H) 7.40 (d, 1H) 7.16 (t, 1H) 6.36 (s, 1H) 2.51 (s, 3H) 2.30 (s, 3H). MS (ES+) m/z 494.18 [M+1]+.

Reference： [1]Patent: US2010/125082,2010,A1 .Location in patent: Page/Page column 49

5
[ 872041-86-6 ]
[ 1231307-83-7 ]
[ 1231304-56-5 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of tert-butyl 2-(((ls,4s)-4-((4-iodo-5-(methylthio)-3-phenyl-lH-pyrazol-l- yl)methyl)cyclohexyl)methoxy)acetate (500 mg, 0.898 mmol) in dioxane (5 mL) was added 5- fluoropyridin-3-ylboronic acid (127 mg, 0.898 mmol) followed by Pd(PPh3)4 (51.9 mg, 0.045 mmol) and K2CO3 (248 mg, 1.797 mmol) at room temperature. The reaction was heated under microwave irradiation at 120 0C for 1.5 h. The reaction mixture was extracted with ethyl acetate and the organic extracts were concentrated under reduced pressure. The residue was treated with 4.0 M HCl (11.23 mL, 44.9 mmol) in dioxane for 5 h. The mixture was concentrated under reduced pressure and the residue was purified by EtaPLC to give the title compound as a solid. The solid was dissolved in acetonitrile (ImL) and water (2 mL) and added 1.0 eq. of NaOH in H2O (1 mL). The mixture was concentrated under reduced pressure to give the sodium salt of the title compound (210 mg). LCMS mlz = 470.2 [M+H]+; 1H NMR (400 MHz, DMSO-^6) delta ppm 1.39-1.58 (m, 8H), 1.74-1.80 (m, IH), 2.20 (s, 3H), 2.21-2.31 (m, IH), 3.31 (d, J= 7.0 Hz, 2H), 3.73 (s, 2H), 4.32 (d, J= 7.5 Hz, 2H), 6.65-7.40 (m, 5H), 7.76-7.70 (m, IH), 8.34 (s, IH), 8.55 (s, IH).

Reference： [1]Patent: WO2010/68242,2010,A1 .Location in patent: Page/Page column 119

6
[ 939793-16-5 ]
[ 872041-86-6 ]
[ 1225218-22-3 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hexamethyldisilazane;nickel(II) iodide; trans-2-aminocyclohexanol hydrochloride; In isopropyl alcohol; at 80℃; for 5h;	In a glove box, a suspension of nickel iodide (37.5 mg, 0.120 mmol), trans-2- aminocyclohexanol hydrochloride (18.2 mg, 0.120 mmol), (5-fluoropyridin-3-yl)boronic acid (282 mg, 2.00 mmol) and sodium bis(trimethylsilyl)amide (367 mg, 2.00 mmol) in isopropyl alcohol (3.30 mL) was allowed to stir for 5 min. i-4a (250 mg, 0.460 mmol) was added, and the resulting mixture was heated to 80 C for 5 h. The reaction mixture was cooled to rt, poured into satd. aq. NH4Cl and extracted with EtOAc. The combined organics were washed with brine, dried (sodium sulfate) and concentrated in vacuo. Purification of the crude residue by flash chromatography on silica gel (gradient elution; 10%-80% EtOAc/hexanes as eluent) afforded the title compound i^b. mlz (ES) 267 (MH)+. 1H NMR (500 MHz, CDCl3): delta 8.39 (d, 1H, J = 2.1 Hz), 8.37 (m, 1H), 7.31 (m, 1H), 3.88 (m, 1H), 3.64 (m, 1H), 3.24-3.52 (m, 3H), 2.35 (m, 1H), 2.01 (m, 1H), 1.51 (s, 9H).
		Step B: Preparation of fers-butyl 3 -(5 -fluoropyridin-3-yl)pyrrolidine-l -carboxylate (i-5b)In a glove box, a suspension of nickel iodide (37.5 mg, 0.120 mmol), trans~2~ aminocyclohexanol hydrochloride (18.2 mg, 0.120 mmol), (5-fiuoropyridin-3-yl)boronic acid (282 mg, 2,00 mmol) and sodium bis(trimethylsilyl)amide (367 mg, 2.00 mmol) in isopropyl alcohol (3.30 mL) was allowed to stir for 5 min. i-5a (250 mg, 0.460 mmol) was added, and the resulting mixture was heated to 80 C for 5 h. The reaction mixture was cooled to rt, poured into satd. aq. NH4Cl and extracted with EtOAc. The combined organics were washed with brine, dried (sodium sulfate) and concentrated in vacuo. Purification of the crude residue by flash chromatography on silica gel (gradient elution; 10%-80% EtOAc/hexanes as eluent) afforded the title compound i^5b. m/z (ES) 267 (MH)+. 1H NMR (500 MHz, CDCl3): delta 8.39 (d, 1H, J = 2.1 Hz), 8.37 (m, 1H), 7.31 (m, 1H), 3.88 (m, 1H), 3.64 (m, 1H), 3.24-3.52 (m, 3H), 2.35 (m, 1H), 2.01 (m, 1H), 1.51 (s, 9H).

Reference： [1]Patent: WO2010/51245,2010,A1 .Location in patent: Page/Page column 38-39
[2]Patent: WO2010/77624,2010,A1 .Location in patent: Page/Page column 37

7
[ 20870-90-0 ]
[ 872041-86-6 ]
[ 1194452-13-5 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;bis(triphenylphosphine)palladium(II)-chloride; In 1,2-dimethoxyethane; ethanol; water; at 150℃; for 0.166667h;Microwave irradiation;	To a solution of 5-fluoropyridine-3-boroniotac acid (CASNo. 872041-86-6, 80mg, 0 57mmol) in 1 ,2-dimethoxyethane (0 7 mL) was added water (0.3 mL) and ethanol (0,2 mL). The solution was then charged with sodium carbonate (60 mg, 0.57mmol), 5-bromo-1-methyl- 1 ,3-dihydro-mdol-2-one (CASNo. 20870-90-0, 132 mg, 0.57 mrnol), and diotachlorobis(triphenylphosphiotane)palladium (II) (CASNo. 13965-03-2, 20.3 mg, 0 029 mmol) The reaction vessel was sealed and is heated by microwave irradiation at 150 C for 10 minutes. The reaction mixture was cooled to room temperature, filtered and concentrated. The resulting residue was partially punfied by semi-preparative reverse phase HPLC (20 to 90% acetonitrile/water w/ 0.1% TFA) Final purification was accomplished via silica gel flash chromatography (methanol-dichloromethane. 0 to 7%) to afford 5-(5-fluoro-pyriotadin-3-yl)-1-methyl-1 3-dihydro-iotandol-2-one; MS. (ES+) m/z 243 (M+Hr; 1H NMR (400 MHz, DMSO-Cf6) delta ppm 3 18 (s, 3 H) 3,64 (s, 2 H), 7 13 (d, J-7.% Hz1 1 H), 7,73 - 7 77 (m, 2 H)1 8.03 (d, J=9 7 Hz, 1 H), 8 53 (d, J=2 7 Hz, 1 H), 8.79 (s, 1 H),

Reference： [1]Patent: WO2010/130794,2010,A1 .Location in patent: Page/Page column 54

8
[ 872041-86-6 ]
[ 138647-49-1 ]
[ 1137950-22-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In acetonitrile; at 80℃; for 12h;	Referential Example 3-18 Synthesis of tert-butyl 5-fluoro-3',6'-dihydro-3,4'-bipyridine-1'(2'H)-carboxylate To an acetonitrile solution (10 ml) of the compound (1.23 g) obtained in Referential Example 3-1, <strong>[872041-86-6](5-fluoropyridin-3-yl)boronic acid</strong> (262 mg), tetrakistriphenylphosphine palladium (107 mg) and a 0.4 M aqueous sodium carbonate solution (10 ml) were added and the resultant mixture was stirred at 80 C. for 12 hours. After adding water, the liquid reaction mixture was extracted with ethyl acetate. The organic layer was washed with water and a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate. Then, the organic layer was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (hexane:ethyl acetate-100:0 to 75:25). Thus, the title compound (445 mg) was obtained as a mixture with piperidone. ESI-MS Found: m/z 279[M+Na]+

Reference： [1]Patent: US2010/324049,2010,A1 .Location in patent: Page/Page column 30

9
[ 872041-86-6 ]
[ 1262441-51-9 ]
[ 1262440-04-9 ]

Yield	Reaction Conditions	Operation in experiment
		To a mixture of 3-iodo-6-methyl-2-[1-(9H-purin-6-ylamino)propyl]-4H-pyrido[1,2-a]pyrimidin-4-one (0.030 g, 0.065 mmol) and <strong>[872041-86-6](5-fluoropyridin-3-yl)boronic acid</strong> (Combi-Blocks, 11.0 mg, 0.0780 mmol) in 1,4-dioxane (0.5 mL) was added a 1 M solution of sodium carbonate (8.27 mg, 0.0780 mmol) in water (0.077 mL) and tetrakis(triphenylphosphine)palladium (0) (3.76 mg, 0.00325 mmol). The reaction mixture was heated at 100 C. overnight. After cooling to rt, the mixture was diluted with EtOAc, washed with water, brine, dried over MgSO4, and concentrated. The residue was purified on RP-HPLC at pH 10 conditions (XBridge C18 column, eluding with a gradient of acetonitrile/water containing 0.15% NH4OH) to provide the desired product. LCMS calculated for C22H20FN8O (M+H)+: m/z=431.2; Found: 431.3.

Reference： [1]Patent: US2011/15212,2011,A1 .Location in patent: Page/Page column 24-25

10
[ 872041-86-6 ]
[ 1259520-31-4 ]
[ 1259520-32-5 ]

Yield	Reaction Conditions	Operation in experiment
	With cesium fluoride;copper(l) iodide; bis(tri-tert-butylphosphine)palladium(0); In 1,2-dimethoxyethane; at 100℃; for 3h;	A mixture of 2-acetyl-6-fluoroquinolin-3-yl trifluoromethanesulfonate (561 mg, 1.66 mmol), <strong>[872041-86-6]5-fluoropyridin-3-ylboronic acid</strong> (258 mg, 1.83 mmol), bis(tri-t-butylphosphine)palladium (0) (85 mg, 166 mumol), cesium fluoride (758 mg, 4.99 mmol) and copper(I) iodide (63 mg, 333 mumol) in DME (10 mL) was heated at 100 C. for 3 h, and then cooled to rt, and filtered. The filtrates were collected washed with EtOAc and concd. Purification of the residue by flash chromatography over silica gel, gradient elution, 0-60% EtOAc in hexane, gave 1-(6-fluoro-3-(5-fluoropyridin-3-yl)quinolin-2-yl)ethanone. Mass Spectrum (ESI) m/e=285.0 (M+1).

Reference： [1]Patent: US2010/331306,2010,A1 .Location in patent: Page/Page column 26

11
[ 872041-86-6 ]
[ 1189730-32-2 ]
[ 1259380-35-2 ]

Yield	Reaction Conditions	Operation in experiment
49%		To a sealed Biotage microwave vial was added DME (3 mL) and 2 drops of H2O and the system was sparged with argon for 10 minutes. A second vial was charged with 4-64 (0.08 g, 0.177 mrnol), 5-iluoropyridin-3-ylboromc acid (0.030 g, 0.212 mmol), Na2CO3 (0.037g, 0.354 mmol) and Pd(PPh3)4 (0.02Og, 0.017 mmol). The tube was sealed with a Teflon septum and the DME/H2O mixture above (3 mL) was added. The reaction mixture was sparged with argon for another 5 minutes then heated to 85 C for 12 hours. The reaction was cooled to room temperature and filtered through a thin pad of silica gel and filter agent. The solvent was concentrated and the crude product was purified by silica gel CombiFlash chromatography (eluting with 0 - 10% MeOH in dichloromethane). The material was then purified by semi prep HPLC and lyophilteed from aq. HC1/CH3CN to give compound 5-12 (0.043 g, 0.085 mmol, 49%) as an off white solid. MS (ESI): 469 (M+H)+

Reference： [1]Patent: WO2010/151595,2010,A1 .Location in patent: Page/Page column 78

12
[ 872041-86-6 ]
[ 1260432-26-5 ]
[ 1260432-28-7 ]

Yield	Reaction Conditions	Operation in experiment
64%	With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; water; at 130℃; for 0.25h;Sealed tube; Microwave irradiation;	2-(3-Bromophenyl)-2-(4-methoxy-3-methylphenyl)-5-methyl-2H-imidazol-4-amine (300 mg, 0,81 mmol), <strong>[872041-86-6]5-fluoropyridin-3-ylboronic acid</strong> (300 mg, 2,13 mmol), [1,1'- Bis(diphenylphosphino)ferrocene]palladium(II) chloride (33,1 mg, 0,04 mmol), 2M aqueous potassium carbonate (1,209 mL, 2,42 mmol) and dioxane (4 mL) were mixed in a vial and heated in a microwave reactor at 130 0C for 15 min. The mixture was diluted with MeOH (5 mL), filtered and purified by preparative HPLC. The product was partitioned between saturated aqueous NaHCO3 and DCM. The organic layer was concentrated to give 199 mg of the title compound (64% yield): 1H NMR (500 MHz, DMSO-J6) delta ppm 8.65 (s, 1 H), 8.57 (d, 1 H), 7.92 (dt, 1 H), 7.81 (s, 1 H), 7.49 - 7.67 (m, 2 H), 7.24 - 7.46 (m, 3 H), 6.79 (d, 1 H), 6.60 (br. s., 2 H), 3.70 (s, 3 H), 2.23 (s, 3 H), 2.07 (s, 3 H); MS (ES) m/z 389 [M+ 1]+.

Reference： [1]Patent: WO2011/2407,2011,A1 .Location in patent: Page/Page column 91

13
[ 872041-86-6 ]
[ 1312684-52-8 ]
[ 1312684-65-3 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 100℃;	To a mixture of 2-(l-azidoethyl)-l-bromonaphthalene (0.080 g, 0.29 mmol) and (5- fluoropyridin-3-yl)boronic acid (49.0 mg, 0.348 mmol) in 1 ,4-dioxane (2 mL) was added a 1 M solution of sodium carbonate in water (0.34 mL) and tetrakis(triphenylphosphine)palladium(0) (16.7 mg, 0.0145 mmol). The reaction mixture was heated at 100 C overnight. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed with water and brine, dried over MgS04, and then concentrated. The residue was purified on silica gel, eluting with 0 to 50% EtOAc in hexane, to give the desired product. LCMS calculated for Ci7Hi4FN4(M+H)+: m/z = 293.1 ; found: 293.0.

Reference： [1]Patent: WO2011/75630,2011,A1 .Location in patent: Page/Page column 71-72

14
[ 872041-86-6 ]
[ 1338484-01-7 ]
[ 1338484-00-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 110℃; for 2h;Microwave irradiation;	A solution of <strong>[872041-86-6]5-fluoropyridin-3-ylboronic acid</strong> (0.096 g, 0.68 mmol), (S)-benzyl 1-(6-fluoro-3-iodoimidazo[1,2-a]pyridin-2-yl)ethylcarbamate (0.200 g, 0.455 mmol), sodium carbonate (0.145 g, 1.366 mmol), and 1,1'-bis(diphenylphosphino)ferrocene palladium (II) chloride, 1:1 complex with DCM (0.019 g, 0.023 mmol) in dioxane (2.53 mL) and water (0.50 mL) was stirred at 110 C. under microwave irradiation for 2 h. Purification by MPLC (eluted with a gradient of 10-60% EtOAc in hexanes) afforded crude (S)-benzyl 1-(6-fluoro-3-(5-fluoropyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)ethylcarbamate as an off-white foam. LC-MS (ESI) m/z 409.1 [M+H]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 431 - 447
[2]Patent: US2011/245257,2011,A1 .Location in patent: Page/Page column 78

15
[ 872041-86-6 ]
[ 1338485-30-5 ]
[ 1338485-31-6 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine;copper diacetate; In dichloromethane; at 20℃; for 1368h;	To a flask was added (S)-tert-butyl 1-(5,6-difluoro-1H-benzo[d]imidazol-2-yl)-ethylcarbamate (0.506 g, 1.70 mmol), <strong>[872041-86-6]5-fluoropyridine-3-boronic acid</strong> (0.480 g, 3.40 mmol), DCM (22.7 mL) and pyridine (0.28 mL, 3.4 mmol), and copper (II) acetate (0.464 g, 2.55 mmol). The mixture was stirred at rt for 57 days. The mixture was then partitioned with satd. aq. ammonium chloride solution (50 mL) and DCM (50 mL). The organic layer was washed with satd. aq. ammonium chloride solution (1×50 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 0% to 20% EtOAc in hexane, to provide a mixture of (S)-tert-butyl 1-(5,6-difluoro-1-(5-fluoropyridin-3-yl)-1H-benzo[d]imidazol-2-yl)ethylcarbamate and (5)-tert-butyl 1-(5,6-difluoro-1-(5-fluoropyridin-3-yl)-1H-benzo[d]imidazol-2-yl)ethylcarbamate as a solid: LC-MS (ESI) m/z 393.1 [M+H]+.

Reference： [1]Patent: US2011/245257,2011,A1 .Location in patent: Page/Page column 106

16
[ 872041-86-6 ]
[ 1354290-08-6 ]
5,7-difluoro-N-(5'-fluoro-6-morpholino-3,3'-bipyridin-4-yl)-3-methyl-2-(pyridin-2-yl)quinolin-4-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate; tricyclohexylphosphine;tris-(dibenzylideneacetone)dipalladium(0); In 1,4-dioxane; water; at 90℃; for 19h;	N-(5-bromo-2-morpholinopyridin-4-yl)-5,7-difluoro-3-methyl-2-(pyridin-2-yl)- quinolin-4-amine (58.8 mg, 0.11 mmol), <strong>[872041-86-6]5-fluoropyridin-3-ylboronic acid</strong> (32.3 mg, 0.23 mmol), tricyclohexylphosphine (5.6 mg, 0.02 mmol), and tris(dibenzyl- ideneacetone)dipalladium (0) (8.7 mg, 9.5 muiotaetaomicron) were added to a flask then degassed and backfilled with argon. To the flask, 1,4-dioxane (3.0 mL) and aq. 1.3M potassium phosphate tribasic (0.18 mL, 0.23 mmol) were added by syringe. The resulting reaction was heated to 90 C and monitored with TLC and LC-MS. After 19 h, the reaction was cooled to rt then poured into water. After extracting twice with EtOAc and twice with DCM, the combined organic extractions were dried over anhydrous magnesium sulfate. After filtration and concentration, the residue was purified on silica gel (0-40% of a premixed solution of 89:9: 1 DCM: MeOH: ammonium hydroxide in DCM) to afford a film that was triturated with MeOH to afford a solid as 5,7-difluoro-N-(5'-fluoro-6-morpholino-3,3'-bipyridin- 4-yl)-3-methyl-2-(pyridin-2-yl)quinolin-4-amine. 1H NMR (500 MHz, DMSO- d6) delta ppm 8.71 (1 H, d, J=4.2 Hz), 8.54 (2 H, m), 8.21 (1 H, s), 8.02 (1 H, td, J=7.7, 1.7 Hz), 7.94 (2 H, m), 7.74 (2 H, m), 7.57 (2 H, m), 5.68 (1 H, s), 3.61 (4 H, t, J=4.8 Hz), 3.27 (4 H, m), 2.26 (3 H, s). Mass Spectrum (pos.) m/e: 529.2 (M+H)+.

Reference： [1]Patent: WO2012/3283,2012,A1 .Location in patent: Page/Page column 161-162

17
[ 626-05-1 ]
[ 872041-86-6 ]
[ 1256039-51-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 90℃; for 2h;	4.2. 6-Bromo-5'-fluoro-[2,3']bipyridyl; Added to a solution of 2.00 g (8.44 mmol) of 2,6-dibromo-pyridine in 80 ml of a 4/1 mixture of toluene and ethanol, are 1.18 g (8.44 mmol) of <strong>[872041-86-6]5-fluoropyridine-3-boronic acid</strong>, 0.48 g (0.42 mmol) of Pd(PPh3)4 and 25 ml of a 1M aqueous solution of sodium carbonate. The mixture is stirred at 90 C. for 2 hours.It is allowed to return to room temperature, the aqueous phase is extracted several times with ethyl acetate. The combined organic phases are dried over sodium sulphate, filtered and evaporated to dryness. The residue thus obtained is purified on a silica gel column, eluting with a 99/1 to 97/3 mixture of dichloromethane and methanol. 0.80 g of product is thus obtained in the form of a white solid.Melting point ( C.): 122-124 C.LC-MS: M+H=2531H NMR (DMSO) delta (ppm): 9.10 (s, 1H), 8.72 (s, 1H), 8.30 (d, 1H), 8.20 (d, 1H), 7.92 (t, 1H), 7.75 (s, 1H).

Reference： [1]Patent: US2012/136026,2012,A1 .Location in patent: Page/Page column 7

18
[ 872041-86-6 ]
[ 1382996-41-9 ]
[ 1382993-90-9 ]

Yield	Reaction Conditions	Operation in experiment
		Step 6. N-{1-[5-Chloro-3-(5-fluoropyridin-3-yl)-2-methoxy-4-methylphenyl]ethyl}-9H-purin-6-amine Into a microwave vial was added N-[1-(3-bromo-5-chloro-2-methoxy-4-methylphenyl)ethyl]-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (0.046 g, 0.096 mmol), <strong>[872041-86-6](5-fluoropyridin-3-yl)boronic acid</strong> (0.020 g, 0.14 mmol), 10% sodium carbonate solution (0.23 mL, 0.23 mmol), 1,4-dioxane (0.9 mL) and tetrakis(triphenylphosphine)palladium(0) (0.011 g, 0.0096 mmol). The mixture was bubbled with N2 for 5 min and then heated at 100 C. for 2 hours. The cooled reaction was treated directly with 6.0 M hydrogen chloride in water (0.2 mL, 1 mmol) at room temperature for ~30 min. The mixture was diluted with MeOH, filtered and purified on Prep LCMS (XBridge C18 Column, eluting with a gradient of acetonitrile in water with 0.2% ammonium hydroxide, at flow rate of 30 mL/min) to give the desired product. LCMS calculated for C20H19ClFN6O (M+H)+: m/z=413.1. found: 413.1.

Reference： [1]Patent: US2012/157430,2012,A1 .Location in patent: Page/Page column 62

19
[ 872041-86-6 ]
[ 1383847-21-9 ]
[ 1383846-99-8 ]

Yield	Reaction Conditions	Operation in experiment
30%	With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In water; N,N-dimethyl-formamide; at 150℃; for 0.25h;Microwave irradiation;	Example 19 5-(3-Amino-4-fluoro-1-(3-(5-fluoropyridin-3-yl)phenyl)-1H-isoindol-1-yl)-1,3-dimethylpyridin-2(1H)-one 5-(3-Amino-1-(3-bromophenyl)-4-fluoro-1H-isoindol-1-yl)-1,3-dimethylpyridin-2(1H)-one (180 mg, 0.42 mmol, Example 9i method B), <strong>[872041-86-6]5-fluoropyridin-3-ylboronic acid</strong> (77 mg, 0.55 mmol), [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (31 mg, 0.04 mmol), potassium carbonate (2 M, aq.) (0.633 mL, 1.27 mmol) and DMF (3 mL) were added to a vial, and microwaved for 15 min at 150 C. The reaction mixture was diluted with brine, NaHCO3 (aq. sat.) and EtOAc. The phases were separated. The aqueous phase was extracted with EtOAc (*3), the combined organics were dried (Na2SO4), filtered and concentrated. Purification by preparative chromatography gave the title compound (56 mg, 30% yield). 1H NMR (500 MHz, DMSO-d6) delta ppm 1.93 (s, 3H), 3.36 (s, 3H), 6.54 (br. s., 2H), 7.21-7.29 (m, 3H), 7.41-7.48 (m, 2H), 7.52 (td, 1H), 7.60-7.66 (m, 2H), 7.71 (d, 1H), 7.92-7.99 (m, 1H), 8.57 (d, 1H), 8.67 (t, 1H); MS (ES+) m/z 443 [M+H]+.

Reference： [1]Patent: US2012/165346,2012,A1 .Location in patent: Page/Page column 25

20
[ 872041-86-6 ]
[ 1383847-37-7 ]
[ 1383847-04-8 ]

Yield	Reaction Conditions	Operation in experiment
61%	With caesium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,2-dimethoxyethane; ethanol; water; at 150℃; for 0.333333h;Microwave irradiation;	Example 22 5-(3-Amino-4-fluoro-1-(3-(5-fluoropyridin-3-yl)phenyl)-1H-isoindol-1-yl)-3-(difluoromethyl)-1-ethylpyridin-2(1H)-one 5-(3-Amino-1-(3-bromophenyl)-4-fluoro-1H-isoindol-1-yl)-3-(difluoromethyl)-1-ethylpyridin-2(1H)-one (70 mg, 0.15 mmol, Example 26i), <strong>[872041-86-6]5-fluoropyridine-3-boronic acid</strong> (60 mg, 0.43 mmol), [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) chloride (7 mg, 8.57 mumol), cesium carbonate (144 mg, 0.44 mmol) and DME:EtOH:water (6:3:1) (2.00 mL) were put in a microwave vial and heated at 150 C. in a microwave reactor for 20 min. The reaction mixture was purified by preparative HPLC to give the title compound (44 mg, 61% yield): 1H NMR (400 MHz, DMSO-d6) delta ppm 1.17 (t, 3H), 3.92 (m, 2H), 6.50-6.99 (m, 3H), 7.27 (dd, 1H), 7.41-7.50 (m, 2H), 7.55 (td, 1H), 7.59-7.69 (m, 4H), 7.74 (d, 1H), 7.97 (m, 1H), 8.58 (d, 1H), 8.69 (t, 1H); MS (ES+) m/z 493 (M+H)+, MS (ES-) m/z 491 [M-Hr]-.

Reference： [1]Patent: US2012/165346,2012,A1 .Location in patent: Page/Page column 26

21
[ 872041-86-6 ]
[ 1384082-93-2 ]
[ 1383982-71-5 ]

Yield	Reaction Conditions	Operation in experiment
41%	With potassium phosphate;chloro(2-dicyclohexylphosphino-2?,4?,6?-triisopropyl-1,1?-biphenyl)[2-(2?-amino-1,1?-biphenyl?)]palladium(II); In tetrahydrofuran; at 120℃; for 0.5h;Inert atmosphere; Microwave irradiation; Sealed vial;	Example 20f(1r,4r)-6'-(5-Fluoropyridin-3-yl)-4-methoxy-5''-methyl-3'H-dispiro[cyclohexane-1,2'-indene-1',2''-imidazol]-4''-amine; 5-Fluoropyridin-3-ylboronic acid (48 mg, 0.34 mmol) and precatalyst 13 (see below) 8.36 mg, 10.63 mumol) was added to a microwave vial. The vial was sealed and evacuated with argon (repeated 3 times). (1r,4r)-6'-Bromo-4-methoxy-5''-methyl-3'H-dispiro[cyclohexane-1,2'-indene-1',2''-imidazol]-4''-amine (Example 19 Method B Step 4, 80.0 mg, 0.21 mmol) dissolved in degassed THF (0.5 mL) was added via a syringe. Degassed 0.5 M K3PO4 solution (1.276 mL, 0.64 mmol) was added via a syringe. The vial was heated in a microwave reactor at 120 C. for 15 min. THF (1.5 mL) and precatalyst 13 (FIG. 1) (8.36 mg, 10.63 mumol) was added. The is reaction was evacuated and backfilled with argon. The solution was stirred in r.t. for approx. 10 min and then heated using MW for 15 min at 120 C. The solvent was evaporated. The crude product was purified using preparative chromatography to give the title compound (34.5 mg, 41% yield), 1H NMR (500 MHz, CD3CN) delta ppm 1.05-1.14 (m, 1H), 1.23-1.35 (m, 2H), 1.44 (td, 1H), 1.50-1.57 (m, 2H), 1.84-1.91 (m, 2H), 2.20 (s, 3H), 3.00 (tt, 1H), 3.09 (d, 1H), 3.17 (d, 1H), 3.25 (s, 3H), 5.27 (br. s., 2H), 6.92 (d, 1H), 7.41 (d, 1H), 7.51 (dd, 1H), 7.65-7.71 (m, 1H), 8.40 (d, 1H), 8.60 (t, 1H), MS (MM-ES+APCI)+m/z 393.2 [M+H]+.

Reference： [1]Patent: US2012/165347,2012,A1 .Location in patent: Page/Page column 58

22
[ 872041-86-6 ]
[ 1392839-23-4 ]
[ 1392839-26-7 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate;tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 100℃; for 16h;Inert atmosphere;	a) 7-Benzyl-l-(5-fluoro-pyridin-3-yl)-4-hydroxy-8-oxo-7, 8-dihydro-[2, 7]naphthyridine-3- carboxylic acid methyl ester[0299] A mixture of 7-benzyl-4-hydroxy-l -iodo-8-oxo-7,8-dihydro-[2,7]naphthyridine-3- carboxylic acid methyl ester (117 mg, 0.27 mmol), <strong>[872041-86-6]5-fluoropyridine-3-boronic acid</strong> (45 mg, 0.32 mmol), Cs2C03 (175 mg, 0.54 mmol) and Pd(PPh3)4 (31 mg, 0.027 mmol) in 5 mL of DMF was heated at 100C for 16 h under N2 atmosphere. After the mixture was cooled to r.t., EtOAc (50 mL) and brine (10 mL) were added. 1 M HCl was added with stirring until pH was about4. The aqueous layer was extracted with additional EtOAc, and the combined organic layer was dried over MgS04 and concentrated. The crude product was purified by silica gel chromatography (5- 70% EtOAc/hexanes) to give 61 mg of the title compound. MS: (+) m/z 405.97 (M+l).

Reference： [1]Patent: WO2012/106472,2012,A1 .Location in patent: Page/Page column 110-111

23
[ 872041-86-6 ]
[ 1392839-51-8 ]
[ 1392839-52-9 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate;tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 100℃; for 16h;Inert atmosphere;	b) l-Benzyl-5-(5-fluoro^yridin-3-yl)-8-hydroxy-2-oxo-l,2-dihydro-[l,6]naphthyridine-7- carboxylic acid methyl ester[0365] A mixture of 1 -benzyl-5-bromo-8-hydroxy-2-oxo-l ,2-dihydro-[l ,6]naphthyridine-7- carboxylic acid methyl ester (70 mg, 0.18 mmol), 5-fluoro-pyridine-3-boronic acid (30 mg, 0.22 mmol), Pd(PPh3)4 (21 mg, 0.018 mmol) and Cs2C03 (1 17 mg, 0.36 mmol) in DMF (4 mL) was heated at 100C for 16 h under nitrogen atmosphere. After cooling to r.t, EtOAc (50 mL) and brine (10 mL) were added. 1 M HC1 was added until pH about 4. The aqueous layer was extracted with additional EtOAc, and the organic layers were combined, washed with water, and dried over MgS04. After evaporating the solvent, the crude product was purified by silica gel chromatography (0-70% EtOAc/hexanes + 2%> AcOH) to give 45 mg of the title compound. MS: (+) m/z 406.33 (M+l).

Reference： [1]Patent: WO2012/106472,2012,A1 .Location in patent: Page/Page column 131

24
7-bromo-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline [ No CAS ]
[ 872041-86-6 ]
[ 1404366-08-0 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; water; at 90℃; for 4h;Inert atmosphere;	To a stirred solution of 7-bromo-4,5-dihydro-[l,2,4]triazolo[4,3-a]quinoline (74- 5; 0.146 g, 0.0005mol) and <strong>[872041-86-6](5-fluoropyridin-3-yl)boronic acid</strong> (0.122 g, 0.0008 mol) in the mixture of 1,4-dioxan (3 mL) and water (3 mL), was added sodium carbonate (0.184 g , 0.0015 mol). Reaction mass was purged with argon for 20 min. Then catalystPd(dppf)2Cl2 (0.023 g, 0.00002 mol) was added and allowed to stir at 90 C for 4 h. The reaction mixture was filtered through CELITE and filter bed was thoroughly washed with ethyl acetate. The collected organic parts were concentrated under vacuum to afford the crude compound, which was purified by silica gel column chromatography to obtain title compound (74). 1HNMR (400 MHz, DMSO-c¾ delta 9.29 (s, 1 H), 8.85 (s, 1 H), 8.577- 8.572 (d, J = 2 Hz, 1 H), 8.12-8.09 (d, J = 12 Hz, 1 H), 7.92-7.89 (m, 1 H), 7.87-7.83 (m, 2 H), 3.11 (s, 4 H). MS (M+1): 267.1.

Reference： [1]Patent: WO2012/148808,2012,A1 .Location in patent: Page/Page column 108; 109

25
[ 872041-86-6 ]
[ 1404367-65-2 ]
[ 1404366-83-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; water; at 80℃; for 12h;Inert atmosphere;	To a stirred solution of 7-bromo-6-chloro-l-methyl-4,5-dihydro- [l,2,4]triazolo[4,3-a]quinoline (143-7; 0.20 g, 0.0006 mol) and (5-fluoropyridin-3- yl)boronic acid (0.93 g, 0.0006 mol) in the mixture of 1,4-dioxan (10 mL) and water (10 mL) was added sodium carbonate (0.127 g, 0.0012 mol). Reaction mass was purged with argon for 20 min. Then catalyst Pd(dppf)2Cl2 (0.048 g, 0.00006 mol) was added and allowed to stir at 80 C for 12 h. The reaction mixture was filtered through CELITE bed and filter bed was thoroughly washed with ethyl acetate. The collected organic part was concentrated under vacuum to afford the crude compound, which was purified by silica gel column chromatography to obtain title compound. 1H NMR (400 MHz, DMSO-a ) delta 8.659-8.652 (d, J= 2.8 Hz, 1 H), 8.514 (s, 1 H), 7.908-7.884 (d, J= 9.6 Hz, 1 H), 7.789- 7.768 (d, J= 8.4 Hz, 1 H), 7.566-7.504 (d, J= 8.4 Hz, 1 H), 3.186-3.152 (m, 2 H), 3.084- 3.035 (m, 2 H), 2.695 (s, 3 H). MS (M+l): 315.1.

Reference： [1]Patent: WO2012/148808,2012,A1 .Location in patent: Page/Page column 131

26
[ 872041-86-6 ]
[ 1404367-68-5 ]
[ 1404366-85-3 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; water; at 80℃; for 12h;Inert atmosphere;	To a stirred solution of 7-bromo-l-methyl-4,5-dihydro-[l,2,4]triazolo[4,3- a]quinoline-6-carbonitrile (145-4; 0.20 g, 0.0006 mol) and <strong>[872041-86-6](5-fluoropyridin-3-yl)boronic acid</strong> (0.97 g, 0.0006 mol) in the mixture of 1,4-dioxan (10 mL) and water (10 mL) was added sodium carbonate (0.190 g, 0.0018). Reaction mass was purged with argon for 20 min. Then catalyst Pd(dppf)2Cl2 (0.048 g, 0.00006 mol) was added and allowed to stir at 80 C for 12 h. The reaction mixture was filtered through celite bed and filter bed was thoroughly washed with ethyl acetate. The collected organic part was concentrated under vacuum to afford the crude compound, which was purified by silica gel column chromatography to obtain title compound. 1H NMR (400 MHz, DMSO-i¾ delta 8.739-8.732 (d, J= 2.8 Hz, 1 H), 8.685 (s, 1 H), 8.095-8.066 (d, J= 11.6 Hz, 2 H), 7.782-7.742 (d, J= 8 Hz, 1 H), 3.282-3.240 (t, J= 8.8 Hz, 2 H), 3.143-3.109 (t, J= 7.6 Hz, 2 H), 2.702 (s, 3 H). MS (M+l): 306.1

Reference： [1]Patent: WO2012/148808,2012,A1 .Location in patent: Page/Page column 133

27
[ 872041-86-6 ]
[ 1404367-75-4 ]
[ 1404366-87-5 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; water; at 80℃; for 12h;Inert atmosphere;	To a stirred solution of 7-bromo-6-cyclopropyl-l-methyl-4,5-dihydro- [l,2,4]triazolo[4,3-a]quinoline (147-8; 0.250 g, 0.00082 mol) and (5-fluoropyridin-3- yl)boronic acid (0.126 g, 0.009 mol) in the mixture of 1,4-dioxane (10 mL) and water (10 mL) was added sodium carbonate (0.260 g, 0.00246 mol). Reaction mass was purged with argon for 20 min. Then catalyst Pd(dppf)2Cl2 (0.066 g, 0.000082 mol) was added and allowed to stir at 80 C for 12 h. The reaction mixture was filtered through CELITE bed and filter bed was thoroughly washed with ethyl acetate. The collected organic layer was concentrated under vacuum to afford the crude compound, which was purified by silica gel column chromatography to obtain title compound. 1H NMR (400 MHz, DMSO- d6) delta 8.587-8.580 (d, J = 2.8 Hz, 1 H), 8.548 (s, 1 H), 7.881-7.856 (d, J= 10 Hz, 1 H), 7.679-7.658 (d, J= 8.4 Hz, 1 H), 7.401-7.380 (d, J= 8.4 Hz, 1 H), 3.237-3.203 (t, J= 6.8 Hz, 2 H), 3.050-3.016 (t, J= 7.2 Hz, 2 H), 2.671 (s, 3 H), 2.175 (s, 1 H), 0.759-0739 (d, J= 8 Hz, 2 H), 0.034-0.022 (d, J= 4.8 Hz, 2 H), MS (M+l): 321.2

Reference： [1]Patent: WO2012/148808,2012,A1 .Location in patent: Page/Page column 140

28
[ 872041-86-6 ]
[ 1428066-17-4 ]
[ 1428066-19-6 ]

Yield	Reaction Conditions	Operation in experiment
88%	With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 90℃; for 3h;Inert atmosphere;	A solution of 5-bromo-l-(tetrahydro-2H-pyran-2-yl)-N-(6- (trifluoromethyl) pyridin-3-yl)-lH-indazole-3-carboxamide (CXXVIII) (0.469 g, 1 mmol), 5-fluoro-pyridyl-3-boronic acid (CXXIX) (0.156 g, 1.1 mmol), potassium phosphate tribasic (0.318 g, 1.5 mmol) and water (degassed, 1 mL) in DMF (10 mL) was purged with argon. Tetrakis(triphenylphosphine)palladium(0) (0.034 g, 0.03 mmol) was added and the solution was purged again with argon. The reaction was heated to 90C for 3 h when TLC showed disappearance of starting material. The solution was cooled to room temperature and excess solvent was removed under vacuum. The residue was treated with water, sonicated briefly and the solids formed were filtered. The solids were washed with cold water and dried under vacuum at room temperature which was purified by silica gel column chromatography (2:8 EtOAc:hexanes? 3:7 EtOAc:hexanes) to afford 5-(5-fluoropyridin-3-yl)-l-(tetrahydiO-2H-pyran-2-yl)-N-(6-(trifluoromethyl) pyridin-3-yl)-lH-indazole-3-carboxamide (CXXX) as a white solid (427 mg, 0.88 mmol, 88% yield). 1H MR (DMSO-d6) delta ppm 10.95 (s, 1H), 9.25 (d, J= 1.8 Hz, 1H), 8.85 (m, 1H), 8.63 (d, J = 1.8 Hz, 1H), 8.61 (d, J= 2.1 Hz, 1H), 8.53 (m, 1H), 8.16-8.13 (m, 1H), 8.08 (d, J= 7.1 Hz, 1H), 7.97-7.94 (m, 2H), 6.11 (dd, J= 8.1, 1.8 Hz, 1H), 4.01 (m, 1H), 3.88-3.83 (m, 1H), 2.63-2.60 (m, 1H), 2.11-2.07 (m, 2H), 1.83-1.80 (m, 1H). 1.69-1.65 (m, 2H); ESIMS found for C24Hi9F4N502 m/z 486.0 (M+H).
88%	In water; N,N-dimethyl-formamide; at 90℃;	A solution of 5-bromo-l-(tetrahydro-2H-pyran-2-yl)-N-(6- (trifluoromethyl) pyridin-3-yl)-lH-indazole-3-carboxamide (CXXVIII) (0.469 g, 1 mmol), 5- fluoro-pyridyl-3-boronic acid (CXXIX) (0.156 g, 1.1 mmol), potassium phosphate tribasic (0.318 g, 1.5 mmol) and water (degassed, 1 mL) in DMF (10 mL) was purged with argon. Tetrakis(triphenylphosphine)palladium(0) (0.034 g, 0.03 mmol) was added and the solution was purged again with argon. The reaction was heated to 90C for 3 h when TLC showed disappearance of starting material. The solution was cooled to room temperature and excess solvent was removed under vacuum. The residue was treated with water, sonicated briefly and the solids formed were filtered. The solids were washed with cold water and dried under vacuum at room temperature which was purified by silica gel column chromatography (2:8 EtOAc:hexanes? 3:7 EtOAc:hexanes) to afford 5-(5-fluoropyridin-3-yl)-l-(tetrahydro-2H- pyran-2-yl)-N-(6-(trifluoromethyl) pyridin-3-yl)-lH-indazole-3-carboxamide (CXXX) as a white solid (427 mg, 0.88 mmol, 88% yield). NMR (DMSO-d6) delta ppm 10.95 (s, 1H), 9.25 (d, J = 1.8 Hz, 1H), 8.85 (m, 1H), 8.63 (d, J= 1.8 Hz, 1H), 8.61 (d, J = 2.1 Hz, 1H), 8.53 (m, 1H), 8.16-8.13 (m, 1H), 8.08 (d, J= 7.1 Hz, 1H), 7.97-7.94 (m, 2H), 6.11 (dd, J= 8.1, 1.8 Hz, 1H), 4.01 (m, 1H), 3.88-3.83 (m, 1H), 2.63-2.60 (m, 1H), 2.11-2.07 (m, 2H), 1.83-1.80 (m, 1H). 1.69-1.65 (m, 2H); ESIMS found for C24H19F4N5O2 mlz 486.0 (M+H).

Reference： [1]Patent: WO2013/40215,2013,A1 .Location in patent: Paragraph 00359
[2]Patent: WO2018/75858,2018,A1 .Location in patent: Paragraph 0390; 0392

29
[ 872041-86-6 ]
[ 1450631-57-8 ]
[ 1450631-58-9 ]

Yield	Reaction Conditions	Operation in experiment
66.6%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; cesium fluoride; In methanol; at 120℃; for 0.416667h;Inert atmosphere; Microwave irradiation;	General procedure: 2-(3-Bromophenyl)imidazo[1,2-a]pyridine-8-carboxamide (1 g, 3.16 mmol) was added to a microwave vial (10-15 ml) and <strong>[872041-86-6]5-fluoropyridin-3-ylboronic acid</strong> (0.446 g, 3.16 mmol),1,1'-bis(diphenylphosphino)ferrocenedichloro palladium(II) dichloromethane complex (0.116 g, 0.16 mmol) and CsF (1.441 g, 9.49 mmol), and MeOH (10mL) were added to the reaction mixture. It was then purged with nitrogen for 5 min, and the reaction mixture was heated in the microwave for 20 min at 120C. After completion of the reaction, the reaction mixture was filtered through Celite, and the filtrate was evaporated to dryness. The crude material was purified by silica gel chromatography eluting with 0-20% MeOH/DCM to obtain the desired product, 2-(3-(5-fluoropyridin-3-yl)phenyl)imidazo[1,2-a]pyridine-8-carboxamide (0.700 g, 66.6 %).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 4996 - 5001

30
[ 872041-86-6 ]
[ 1611001-28-5 ]
[ 1611000-21-5 ]

Yield	Reaction Conditions	Operation in experiment
47.94%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In water; N,N-dimethyl-formamide; at 120℃; for 2h;Inert atmosphere;	The compound of example 75 (0.1 50 g, 0.42 mmol) was treated with 5-fluoropyridin-3- ylboronic acid (0.077 g, 0.54 mmol) in DMF (20 mL) in presence of [1 ,1 '- bis(diphenylphosphino)ferrocene]dichloro palladium(l l) complex with dichloromethane (0.0343 g, 0.042 mmol) and sodium carbonate (0.356 g, 3.36 mmol) solution in 4 mL of water according to the procedure for the preparation of the compound of example 2 to afford the title compound Yield: 0.1 1 0 g (47.94 %) 1 H NMR (CDCI3, 300 MHz): delta 5.1 6 (s, 2H, NH2), 7.42 (dd, 1 H, J = 9.3 Hz, J = 1 .5 Hz, Ar), 7.63 - 7.67 (m, 1 H, Ar), 7.81 - 7.85 (m, 3H, Ar), 8.36 - 8.42 (m, 2H, Ar), 8.57 (d, 1 H, J = 2.7 Hz), 8.74 (s, 1 H, Ar) ; MS (ES+): m/e 371 .1 (M+1 ).

Reference： [1]Patent: WO2014/80241,2014,A1 .Location in patent: Page/Page column 79

31
[ 872041-86-6 ]
6-[2-chloro-3-(trifluoromethyl)phenyl]carbonyl}-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine [ No CAS ]
6-[2-chloro-3-(trifluoromethyl)phenyl]carbonyl}-3-(5-fluoropyridin-3-yl)-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
42%	With 1,1'-bis-(diphenylphosphino)ferrocene; potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; at 100℃;Inert atmosphere;	Example 95 6-[2-Chloro-3-(trifluoromethyl)phenyl]carbonyl}-3-(5-fluoropyridin-3-yl)-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridine To a solution of 6-[2-Chloro-3-(trifluoromethyl)phenyl]carbonyl}-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine (90 mg, 0.167 mmol) in 1,4-dioxane (1 mL) was added <strong>[872041-86-6]5-fluoropyridine-3-boronic acid</strong> (70 mg, 0.50 mmol), potassium phosphate (106 mg, 0.50 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (18 mg, 0.025 mmol) and 1,1'-bis(diphenylphosphino)ferrocene (6 mg, 0.010 mmol). The reaction was stirred at 100 C. overnight under an atmosphere of N2. The reaction was filtered through Celite and the Celite was washed with EtOAc. The solvent was concentrated and the residue was purified by HPLC (Agilent prep system, Waters XBridge, C18, 5 mum, 30*100 mm column, 5-99% MeOH/20 mM NH4OH over 18 min at 30 mL/min) followed by THP deprotection as described in Example 94 to provide the desired product (30 mg, 42%). MS (ESI) mass calcd. C19H13ClF4N4O, 424.1. m/z found, 425.1 [M+H]+. 1H NMR (500 MHz, CDCl3) delta 8.73-8.64 (d, J=6.1Hz, 1H), 8.48-8.39 (m, 1H), 7.83-7.74 (m, 1H), 7.72-7.60 (m, 1H), 7.56-7.44 (m, 2H), 5.15 (d, J=16.6 Hz, 0.7H), 4.88 (d, J=16.6 Hz, 0.7H), 4.50 (d, J=15.9 Hz, 0.3H), 4.39 (d, J=15.9 Hz, 0.3H), 4.25 (dt, J=12.8, 5.5 Hz, 0.3H), 4.04-3.95 (m, 0.3H), 3.54 (t, J=5.7 Hz, 1.4H), 2.99 (t, J=5.7 Hz, 0.7H), 2.92-2.73 (m, 1.3H).

Reference： [1]Patent: US2014/275015,2014,A1 .Location in patent: Paragraph 0603; 0604

32
[ 872041-86-6 ]
methyl 4-(((trifluoromethyl)sulfonyl)oxy)-1,2,3,6-tetrahydro-[1,1'-biphenyl]-1-carboxylate [ No CAS ]
methyl 4-(5-fluoropyridin-3-yl)-1,2,3,6-tetrahydro-[1,1'-biphenyl]-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	With tetrakis(triphenylphosphine) palladium(0); cesium fluoride; In methanol; 1,2-dimethoxyethane; at 120℃; for 4h;Sealed tube; Microwave irradiation;	Step 2: methyl 4-(5-fluoropyridin-3-yl)-l,2,3,6-tetrahydro-[l,l'-biphenyl]-l-carboxylate Methyl 4-(((trifluoromethyl)sulfonyl)oxy)- 1 ,2,3,6-tetrahydro-[l , l'-biphenyl]- 1- carboxylate (445 mg, 1.22 mmol), 3-fluoropyridine-5-boronic acid (171 mg, 1.22 mmol), CsF (200 mg), DME (12 mL), MeOH (3 mL) and palladium tetrakis(triphenylphosphine) (20 mg) were combined in a sealed tube and microwave heated to 120 C for 4 h. Reaction mixture was allowed to cool to room temperature, evaporated to dryness onto silica and purified by flash chromatography to give the title compound as a white solid (216 mg, 57%). MS (ES+) consistent with target (M+H)+.
57%	With tetrakis(triphenylphosphine) palladium(0); cesium fluoride; In methanol; 1,2-dimethoxyethane; at 120℃; for 4h;Sealed tube; Microwave irradiation;	Step 2: methyl 4-(5-fluoropyridin-3-yl)-1 ,2,3,6-tetrahydro-[1 ,1 '-biphenyl]-1 - carboxylate [00217] Methyl 4-(((trifluoromethyl)sulfonyl)oxy)-1 ,2,3,6-tetrahydro-[1 , 1 '- biphenyl]-1 -carboxylate (445 mg, 1 .22 mmol), 3-fluoropyridine-5-boronic acid (1 71 mg, 1 .22 mmol), CsF (200 mg), DME (12 ml_), MeOH (3 ml_) and palladium tetrakis(triphenylphosphine) (20 mg) were combined in a sealed tube and microwave heated to 120 C for 4 h. The reaction mixture was allowed to cool to r.t., evaporated to dryness onto silica and purified by flash chromatography to give the title compound as a white solid (216 mg, 57%). LCMS (ES+) consistent with target (M+H)+.

Reference： [1]Patent: WO2014/159218,2014,A1 .Location in patent: Page/Page column 104
[2]Patent: WO2014/159224,2014,A1 .Location in patent: Paragraph 00217

33
[ 872041-86-6 ]
methyl 3'-fluoro-2'-methyl-4-(((trifluoromethyl)sulfonyl)oxy)-1,2,3,6-tetrahydro-[1,1'-biphenyl]-1-carboxylate [ No CAS ]
methyl 3'-fluoro-4-(5-fluoropyridin-3-yl)-2'-methyl-1,2,3,6-tetrahydro-[1,1'-biphenyl]-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With tetrakis(triphenylphosphine) palladium(0); cesium fluoride; In methanol; 1,2-dimethoxyethane; at 120℃; for 2h;Sealed tube; Microwave irradiation;	Step 4: methyl 3'-fluoro-4-(5-fluoropyridin-3-yl)-2'-methyl-l,2,3,6-tetrahydro-[l, - bipheny 1] - 1 -c arboxylate Methyl 3'-fluoro-2'-methyl-4-(((trifluoromethyl)sulfonyl)oxy)-l,2,3,6-tetrahydro-[l,r- biphenyl]-l -carboxylate (326 mg, 0.82 mmol), <strong>[872041-86-6]5-fluoropyridine-3-boronic acid</strong> (116 mg, 0.82 mmol), CsF (120 mg), DME (12 mL), MeOH (2 mL) and palladium tetrakis(triphenylphosphine) (10 mg) were combined in a sealed tube and heated by microwave to 120 C for 2 h. The reaction mixture was then evaporated to dryness onto silica and purified by flash chromatography to give the title compound as a crystalline solid (234 mg, 83%). MS (ES+) consistent with target (M+H)+.
83%	With tetrakis(triphenylphosphine) palladium(0); cesium fluoride; In methanol; 1,2-dimethoxyethane; at 120℃; for 2h;Sealed tube; Microwave irradiation;	Step 2: methyl 3'-fluoro-4-(5-fluoropyridin-3-yl)-2'-methyl-1 ,2,3,6-tetrahydro- [1 ,1 '-biphenyl]-1 -carboxylate [00369] Methyl 3'-fluoro-2'-methyl-4-(((trifluoromethyl)sulfonyl)oxy)-1 ,2,3,6- tetrahydro-[1 , 1 '-biphenyl]-1 -carboxylate (326 mg, 0.82 mmol), 5-fluoropyridine-3- boronic acid (1 16 mg, 0.82 mmol), CsF (120 mg), DME (12 mL), MeOH (2 mL) and palladium tetrakis(triphenylphosphine) (10 mg) were combined in a sealed tube and heated by microwave to 120 C for 2 h. The reaction mixture was then evaporated to dryness onto silica and purified by flash chromatography to give the title compound as a crystalline solid (234 mg, 83%). MS (ES+) consistent with target (M+H)+.

Reference： [1]Patent: WO2014/159218,2014,A1 .Location in patent: Page/Page column 106
[2]Patent: WO2014/159224,2014,A1 .Location in patent: Paragraph 00369

34
[ 872041-86-6 ]
(±)-methyl 1-(3-fluoro-2-methyl-phenyl)-3-(trifluoromethylsulfonyloxy)cyclopent-2-ene-1-carboxylate [ No CAS ]
(±)-methyl 1-(3-fluoro-2-methyl-phenyl)-3-(5-fluoropyridin-3-yl)cyclopent-2-ene-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With tetrakis(triphenylphosphine) palladium(0); cesium fluoride; In methanol; 1,2-dimethoxyethane; at 120℃; for 1h;Microwave irradiation;	Step 1 : (+)-methyl l-(3-fluoro-2-methyl-phenyl)-3-(5-fluoropyridin-3-yl)cyclopent-2-ene- 1-carboxylate [00181] A suspension of (+)-methyl l-(3-fluoro-2-methyl-phenyl)-3- (trifluoromethylsulfonyloxy)cyclopent-2-ene-l-carboxylate (prepared using Method A from Intermediate 3, 1.01 g, 2.64 mmol), 3-fluoropyridine-5-boronic acid (376 mg, 2.67 mmol), Pd(PPb-3)4 (153 mg, 0.13 mmol) and CsF (597 mg, 3.93 mmol in 4: 1 v/v DME:MeOH (8.7 mL) was stirred at 120 C for 1 h under microwave irradiation. The mixture was concentrated onto silica and purified by silica column chromatography (gradient elution, 0-100% EtOAc in /so-hexane) to yield the title compound as a white powder (760 mg, 87%). MS (ES+) consistent with target (M+H)+.

Reference： [1]Patent: WO2014/159218,2014,A1 .Location in patent: Paragraph 00181

35
[ 872041-86-6 ]
(S)-methyl 1-(3-fluoro-2-methylphenyl)-3-(((trifluoromethyl)sulfonyl)oxy)cyclopent-2-enecarboxylate [ No CAS ]
(S)-methyl 1-(3-fluoro-2-methylphenyl)-3-(5-fluoropyridin-3-yl)cyclopent-2-enecarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; water; at 100℃; for 2h;Inert atmosphere;	General procedure: Method B (Suzuki coupling) [00174] To a solution of methyl 1 -(3-fluoro-2-methylphenyl)-3- (((trifluoromethyl)sulfonyl) oxy)cyclopent-2-enecarboxylate (0.5 g, 1 .31 mmol) in 1 ,2 dimethoxyethane (8 ml_) was added boronic acid (1 .31 mmol), potassium carbonate (0.362 g, 2.62 mmol) and water (4 ml_). The reaction mixture was heated to 60 C at which time a colorless solution formed. [1 ,1 '- Bis(diphenylphosphino)ferrocene] dichloropalladium(ll), complex with dichloromethane (0.06 g, 0.07 mmol) was added and the reaction mixture was heated to 80 C under N2 for 2 h. After this time the reaction mixture was cooled to r.t. and filtered through Celite, washing with EtOAc (3 x 10 ml_). Combined organics were extracted with water (1 5 ml_) then brine (20 ml_). EtOAc layers were then dried, filtered (phase separation cartridge) and concentrated to give a brown residue.

Reference： [1]Patent: WO2014/159224,2014,A1 .Location in patent: Paragraph 00174; 00204

36
[ 872041-86-6 ]
tert-butyl 7-chloro-3,4-dihydro-1,4-ethanopyrido[2,3-b][1,4]diazepine-5(2H)-carboxylate [ No CAS ]
tert-butyl 7-(5-fluoropyridin-3-yl)-3,4-dihydro-1,4-ethanopyrido[2,3-b][1,4]diazepine-5(2H)-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 110℃; for 12h;	This moiety was made using the following protocol. To a degassed mixture of dioxane/water (30 mL/3 mL) was added tert-butyl 7-chloro-3,4-dihydro-l,4- ethanopyrido[2,3-b][l,4]diazepine-5(2H)-carboxylate (1.39 g, 4.5 mmol), (5- fluoropyridin-3-yl)boronic acid (1.27 g, 9.0 mmol), Pd(dppf)Cl2 (0.37 g, 0.45 mmol), and Cs2C03 (4.40 g, 13.5 mmol). The mixture was stirred at 110 C for 12 h, then concentrated and purified by column chromatography (PE/EA = 2/1) to give tert-butyl 7-(5-fluoropyridin-3-yl)-3,4-dihydro- 1 ,4-ethanopyrido[2,3-b] [ 1 ,4]diazepine-5(2H)- carboxylate (1.5 g, 89%). MS (ESI) calcd for C20H23FN4O2: 370.18
89%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 110℃; for 12h;	This moiety was made using the following protocol. To a degassed mixture of dioxane/ water (30 mL/3 mL) was added tert-butyl 7-chloro-3,4-dihydro-1,4-ethanopyrido[2,3-b][1,4]diazepine-5(2H)-carboxylate (1.39 g, 4.5 mmol), <strong>[872041-86-6](5-fluoropyridin-3-yl)boronic acid</strong> (1.27 g, 9.0 mmol), Pd(dppf)Cl2 (0.37 g, 0.45 mmol), and Cs2CO3 (4.40 g, 13.5 mmol). The mixture was stirred at 110 C. for 12 h, then concentrated and purified by column chromatography (PE/EA=2/1) to give tert-butyl 7-(5-fluoropyridin-3-yl)-3,4-dihydro-1,4-ethanopyrido[2,3-b][1,4]diazepine-5(2H)-carboxylate (1.5 g, 89%). MS (ESI) calcd for C20H23FN4O2: 370.18.

Reference： [1]Patent: WO2014/186313,2014,A1 .Location in patent: Page/Page column 165-166
[2]Patent: US2015/152108,2015,A1 .Location in patent: Paragraph 0843; 0844

37
[ 252561-81-2 ]
[ 872041-86-6 ]
1-[2-chloro-4-(5-fluoropyridin-3-yl)phenyl]ethanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
2.5 g	With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; water; toluene; at 100℃; for 8h;Inert atmosphere;	To a solution of <strong>[252561-81-2]1-(4-bromo-2-chlorophenyl)ethanone</strong> (9.7 g, 41.54 mmol) in toluene/dioxane/water (60 mL/20mL/2mL) was added (5-fluoropyridin-3-yl)boronic acid (7.6 g, 54.00 mmol), cesium carbonate (27 g, 83.08 mmol) and Pd(PPli3)4 (4.8 g, 4.154 mmol) under nitrogen. The reaction mixture was heated at 100C for 8 hours, filtrated. The reaction mixture was tehn extracted with EtOAc (50 mL) twice, washed with brine and dried with sodium sulfate and concentrated under vacuo. After purification by flash column chromatography (PE : EA = 10 : 1) this afforded the title compound (2.5 g) as white solid. 1H-NMR (400 MHz, d6-DMSO, Method M1); delta 8.90 (s, 1 H), 8.65 (d, 1 H), 8.22 (d, 1 H), 8.02 (d, 1 H), 7.82 - 7.93 (m, 2 H), 2.63 (s, 3 H) LCMS (M+H)+: 250.0

Reference： [1]Patent: WO2015/78800,2015,A1 .Location in patent: Page/Page column 131

38
[ 872041-86-6 ]
[ 95667-45-1 ]
17-(5-fluoropyridin-3-yl)-3-methoxyestra-1,3,5⁽¹⁰⁾,16-tetraene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; lithium chloride; In ethanol; water; toluene; for 4.5h;Reflux;	1.23 g (0.05 equiv.) of bis(triphenylphosphine)palladium(II) chloride were added to a mixture of 14.6 g (35.1 mmol) of 3-methoxyestra-1,3,5(10),16-tetraen-17-yltrifluoromethanesulphonate (S. Cacchi, E. Morera, Synthesis, 1986, 4, 320-322), 6.92 g (1.4 equiv.) of <strong>[872041-86-6]5-fluoropyridine-3-boronic acid</strong>, 2.97 g (2.0 equiv.) of lithium chloride, 47 ml of 2M aqueous sodium carbonate solution, 80 ml of ethanol and 100 ml of toluene, and the mixture was heated under reflux for 4.5 h. The mixture was filtered through Celite, the phases were separated and the aqueous phase was extracted with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium bicarbonate solution and sodium chloride solution, dried over sodium sulphate and concentrated. The residue was purified by column chromatography on silica gel (hexane/ethyl acetate). This gave 10.4 g (81% of theory) of a solid. C24H26FNO. 1H-NMR (300 MHz, chloroform-d): delta [ppm]=1.05 (s, 3H), 1.40-1.75 (m), 1.82 (td, 1H), 1.90-2.03 (m, 1H), 2.03-2.27 (m), 2.27-2.57 (m), 2.84-3.03 (m, 2H), 3.79 (s, 3H), 5.99-6.18 (m, 1H), 6.66 (d, 1H), 6.73 (dd, 1H), 7.21 (d, 1H), 7.40 (dt, 1H), 8.34 (d, 1H), 8.48 (s, 1H).
81%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; lithium chloride; In ethanol; toluene; for 4.5h;Reflux;	To a mixture of 14.6 g (35.1 mmol) of 3-methoxyestra-1,3,5 (10), 16-tetraen-17-yltrifluormethansulfonat (S. Cacchi, E. Morera, Synthesis, 1986, 4, 320-322), 6.92 g (1.4 equiv.) of <strong>[872041-86-6]5-fluoropyridine-3-boronic acid</strong>, 2.97 g (2.0 equiv.) of lithium chloride, 47 ml of 2M aqueous sodium carbonate solution, 80 ml of ethanol and 100 ml of toluene added to 01.23 g (0.05 equiv.) of bis (triphenylphosphine) palladium (II) chloride and heated for 4.5 h under reflux. It was filtered through Celite, the phases were separated and extracted with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium bicarbonate solution and sodium chloride solution, dried over sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel (hexane / ethyl acetate). This gave 10.4 g (81%. Th.) Of a solid. C 24 H 26 FNO 1 H-NMR (300MHz, chloroform-d):. Delta [ppm] = 1:05 (s, 3H), 1:40 - 1.75 (m), 1.82 (td, 1H), 1.90 - 2:03 (m, 1H), 2:03 to 2:27 (m), 2:27 to 2:57 (m), 2.84 - 3:03 (m, 2H), 3.79 (s, 3H), 5.99 - 6.18 (m, 1H), 6.66 (d, 1H), 6.73 (dd, 1H), 7.21 (d, 1H), 7.40 (dt, 1 H), 8:34 (d, 1 H), 8:48 (s, 1H).

Reference： [1]Patent: US2015/210734,2015,A1 .Location in patent: Paragraph 0175
[2]Patent: KR2015/36319,2015,A .Location in patent: Paragraph 0208-0211

39
[ 872041-86-6 ]
[ 121219-03-2 ]
C₁₁H₆BrF₂NO [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45 mg	With copper diacetate; triethylamine; In dichloromethane; at 20℃; for 16h;	<strong>[121219-03-2]4-bromo-3-fluorophenol</strong> (200 mg, 1.0 mmol, 1.0 equiv), 5-fluoropyridin-3-ylboronic acid (221 mg, 1.5 mmol, 1.5 equiv), copper (II) acetate (190 mg, 0.481 mmol, 1.0 equiv) and 4 A MS were suspended in 10 mE methylene chloride. Triethylamine (530 mg, 5.0 mmol, 5.0 equiv) was then added after which point the reaction turned from blue to brown and was stirred at room temperature for 16 h under ambient atmosphere after which point the reaction turned back blue. The slurry was filtered through a small pad ofcelite and washed with 30% ethyl acetate in hexanes. The combined filtrate was concentrated in vacuo. Purification using flash silica gel chromatography gave the desired biaryl bromide (45 mg) which was converted to boronic acid 297 by Method 1. [M-H]=250. 1 mlz. Activity: A.

Reference： [1]Patent: US2015/368278,2015,A1 .Location in patent: Paragraph 1233

40
[ 872041-86-6 ]
[ 1255095-03-4 ]
[ 1255091-68-9 ]

Yield	Reaction Conditions	Operation in experiment
10.2 g	With tetrakis-(triphenylphosphine)-palladium; potassium carbonate In ethanol; lithium hydroxide monohydrate; toluene for 5.5h; Reflux;	4.1 Preparation of compound A35 To a flask charged with tert-butyl N-(2-bromo-4-methyl-thiazol-5-yl)carbamate (1 1 .31 g, 38.6mmol) and (5-fluoro-3-pyridyl)boronic acid (6.52g, 46.3mmol) was added toluene (151 ml.) and ethanol (75mL). Pd(PPh3)4 (2.20g, 1.90mmol) was added, followed by 2M aq K2C03 (38.6ml_, 77.2mmol). The reaction was heated to reflux for five and a half hours. The reaction mixture was cooled to room temperature and concentrated in vacuo to remove the organics. The mixture was diluted with CHCI3 and washed with water. The organic phase was concentrated in vacuo and the residue purified via flash column chromatography on silica using an EtOAc/isohexane gradient to afford the desired compound (tert-butyl N-[2-(5-fluoro-3-pyridyl)-4-methyl-thiazol-5- yl]carbamate, 10.2g) as a beige solid. 1 H NMR (400MHz, CDCI3) δ = 8.87 (1 H, m), 8.44 (1 H, d), 7.94-7.87 (1 H, m), 6.73 (1 H, br. s), 2.39 (3H, s), 1 .55 (9H, s)
	With palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; Cs₂CO₃ In N,N-dimethyl-formamide at 100℃; for 0.5h; Microwave irradiation;	3 Step 3: PdCl2dppf (52.4 mg, 0.072 mmol) was added at rt to a degassed mixture of tert-butyl (2- bromo-4-methylthiazol-5-yl)carbamate (70 mg, 0.239 mmol), (5-fluoropyridin-3-yl)boronic acid (33.6 mg, 0.239 mmol) and cesium carbonate (389 mg, 1.194 mmol) in DMF (2.5 mL) and the mixture was then heated in a microwave oven at 100 °C for 30 min. After cooling to rt, the reaction mixture was dilluted with ethyl acetate and filtered through a plug of Celite. The crude product was purified by preparative HPLC (Waters X-Bridge C18 OBD, 5 µm, 30*100 mm, Eluent A: H2O + 7.3 mM NH4OH, B: CH3CN + 7.3 mM NH4OH, Gradient: 20 to 99% B in 12.5 min hold 2.5 min, Flow 45 mL/min) to give tert-butyl (2-(5-fluoropyridin-3-yl)-4-methylthiazol-5- yl)carbamate. LCMS (method b) m/z 310.1 [M+H]+, tR = 1.07 min.1 NMR (400 MHz, CDCl3) δ ppm 8.97 - 8.92 (m, 1H), 8.50 - 8.44 (m, 1H), 8.21 (d, J = 8.5 Hz, 1H), 6.80 (s, 1H), 2.44 (s, 3H), 1.56 (s, 9H).
	With palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; Cs₂CO₃ In N,N-dimethyl-formamide at 100℃; for 0.5h; Microwave irradiation;	3 Step 3: PdCl2dppf (52.4 mg, 0.072 mmol) was added at rt to a degassed mixture of tert-butyl (2- bromo-4-methylthiazol-5-yl)carbamate (70 mg, 0.239 mmol), (5-fluoropyridin-3-yl)boronic acid (33.6 mg, 0.239 mmol) and cesium carbonate (389 mg, 1.194 mmol) in DMF (2.5 mL) and the mixture was then heated in a microwave oven at 100 °C for 30 min. After cooling to rt, the reaction mixture was dilluted with ethyl acetate and filtered through a plug of Celite. The crude product was purified by preparative HPLC (Waters X-Bridge C18 OBD, 5 µm, 30*100 mm, Eluent A: H2O + 7.3 mM NH4OH, B: CH3CN + 7.3 mM NH4OH, Gradient: 20 to 99% B in 12.5 min hold 2.5 min, Flow 45 mL/min) to give tert-butyl (2-(5-fluoropyridin-3-yl)-4-methylthiazol-5- yl)carbamate. LCMS (method b) m/z 310.1 [M+H]+, tR = 1.07 min.1 NMR (400 MHz, CDCl3) δ ppm 8.97 - 8.92 (m, 1H), 8.50 - 8.44 (m, 1H), 8.21 (d, J = 8.5 Hz, 1H), 6.80 (s, 1H), 2.44 (s, 3H), 1.56 (s, 9H).

With palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; Cs₂CO₃ In N,N-dimethyl-formamide at 100℃; for 0.5h; Microwave irradiation;

Step 3: PdCl2dppf (52.4 mg, 0.072 mmol) was added at rt to a degassed mixture of tert-butyl (2- bromo-4-methylthiazol-5-yl)carbamate (70 mg, 0.239 mmol), (5-fluoropyridin-3-yl)boronic acid (33.6 mg, 0.239 mmol) and cesium carbonate (389 mg, 1.194 mmol) in DMF (2.5 mL) and the mixture was then heated in a microwave oven at 100 °C for 30 min. After cooling to rt, the reaction mixture was dilluted with ethyl acetate and filtered through a plug of Celite. The crude product was purified by preparative HPLC (Waters X-Bridge C18 OBD, 5 µm, 30*100 mm, Eluent A: H2O + 7.3 mM NH4OH, B: CH3CN + 7.3 mM NH4OH, Gradient: 20 to 99% B in 12.5 min hold 2.5 min, Flow 45 mL/min) to give tert-butyl (2-(5-fluoropyridin-3-yl)-4-methylthiazol-5- yl)carbamate. LCMS (method b) m/z 310.1 [M+H]+, tR = 1.07 min.1 NMR (400 MHz, CDCl3) δ ppm 8.97 - 8.92 (m, 1H), 8.50 - 8.44 (m, 1H), 8.21 (d, J = 8.5 Hz, 1H), 6.80 (s, 1H), 2.44 (s, 3H), 1.56 (s, 9H).

Reference： [1]Current Patent Assignee: Syngenta (in: Sinochem Holdings); SINOCHEM HOLDINGS CORPORATION LTD - WO2016/46078, 2016, A1 Location in patent: Page/Page column 47
[2]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - WO2022/58902, 2022, A1 Location in patent: Page/Page column 100
[3]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - WO2022/58902, 2022, A1 Location in patent: Page/Page column 100
[4]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - WO2022/58902, 2022, A1 Location in patent: Page/Page column 100

41
[ 872041-86-6 ]
tert-butyl N-methyl-N-[17-[(trifluoromethyl)sulfonyl]oxy}estra-1⁽¹⁰⁾,2,4,16-tetraen-3-yl]sulfonyl}-beta-alaninate [ No CAS ]
tert-butyl N-[17-(5-fluoropyridin-3-yl)estra-1⁽¹⁰⁾,2,4,16-tetraen-3-yl]sulfonyl}-N-methyl-beta-alaninate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In 1,4-dioxane; at 90℃; for 2h;Sealed tube;	Example 1 tert-butyl N- [17-(5-fluoropyridin-3-yl)estra-l(10),2,4,16-tetraen-3-yl]sulfonyl}-N-methyl-beta- alaninate To a solution of 655 mg (1.07 mmol) of teri-butyl N-methyl-N- [17- { [(trifluoromethyl)sulfonyl]oxy} estra- 1 (10),2,4, 16-tetraen-3-yl] sulfonyl} -beta-alaninate (Intermediate 2-A) in 6.5 ml of dioxane 258 mg (1.83 mmol) of <strong>[872041-86-6]5-fluoropyridine-3-boronic acid</strong>, 60.5 mg (0.08 mmol) of dichlorobis(triphenylphosphine)palladium(II) and 2.15 ml of 2M sodium carbonate solution were added. The reaction mixture was degassed and then stirred in a sealed tube for 2 hours at 90C. The reaction mixture was allowed to cool to room temperature and partitioned between water and ethyl acetate. The organic phase was further washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by chromatography using a prepacked silica gel cartridge (mobile phase: cyclohexane/ethyl acetate, gradient 0% to 35%). The yield was 525 mg (83% of theory) of the title compound. LC-MS (method A): Rt = 4.89 min; m/z = 555.4 (M+H)+ 1H-NMR (300 MHz, CDC13): delta [ppm] = 1.07 (s, 3H), 1.45 (s, 9H), 1.48 - 1.61 (m, 1H), 1.67 - 1.86 (m, 4H), 1.96 - 2.10 (m, 1H), 2.04 - 2.05 (m, 2H), 2.41 (ddd, 3H), 2.54 (dd, 2H), 2.77 (s, 3H), 3.00 (dd, 2H), 3.29 (dd, 2H), 6.11 (dd, 1H), 7.37 - 7.45 (m, 2H), 7.50 - 7.57 (m, 2H), 8.36 (d, 1H), 8.48 (dd, 1H)

Reference： [1]Patent: WO2016/37956,2016,A1 .Location in patent: Page/Page column 59

42
[ 872041-86-6 ]
[ 115375-60-5 ]
3β-acetoxy-17-(5-fluoropyridin-3-yl)androsta-5,16-diene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%		General procedure: The mixture of 17-trifluoromethanesulfonyl-3beta-acetoxyandrosta-5,16-diene (3) (2.0 g, 4.3 mmol), PdCl2 catalyst (7.63 mg, 0.043 mmol)and CuI (8 mg, 0.043 mol) in PEG-400 (2 mL) and water (12 mL)was stirred at room temperature for 5 min. The resultant mixturewas treated with the arylboronic acid (8.6 mmol) and 2 M sodiumcarbonate (2.2 mL) respectively. The mixture was stirred at 75 C for 5 h, and the completion of reaction was confirmed by TLC (EtOAc/hexanes 1:8). The reaction mixture was then extracted withdichloromethane (10 mL × 2). The organic phase was washed with3% HCl (10 mL), water (10 mL) and brine (5 mL), and dried overanhydrous sodium sulphate. After removal of dichloromethane,the crude product was purified by flash chromatography (silica gel,EtOAc/hexanes, 1/40) to give the desired products 4a-i.

Reference： [1]Journal of Chemical Research,2016,vol. 40,p. 289 - 292

43
[ 872041-86-6 ]
5,5'-difluoro-3,3'-bipyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With copper(II) choride dihydrate; sodium carbonate; In methanol; at 25℃; for 0.25h;Green chemistry;	General procedure: Arylboronic acid (0.3 mmol), CuCl2·2H2O (2.5 mg, 5 mol%), Na2CO3 (10 mol%),methanol (1 mL) were added to a vial. The reaction mixture was stirred at 25 C inthe air for 5-15 min and was monitored by TLC. Then the reaction was quenched withtwo drops of H2O, diluted with 2 mL of ethyl acetate, and filtered over a pad ofMgSO4 and silica. The pad was rinsed with additional ethyl acetate, and the solutionwas concentrated in vacuum. The crude material was loaded onto a silica gel columnand purified by flash chromatography.

Reference： [1]Synlett,2017,vol. 28,p. 601 - 606

44
[ 872041-86-6 ]
tert-butyl 4-(4-(6-chloropyrazin-2-yl)benzoyl)piperazine-1-carboxylate [ No CAS ]
tert-butyl 4-(4-(6-(5-fluoropyridin-3-yl)pyrazin-2-yl)benzoyl)piperazine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%		K2CO3 (53.5g, 387mmol), tert-butyl 4-(4-(6-chloropyrazin-2-yl)benzoyl)piperazine-1 - carboxylate (60g, 149mmol) and <strong>[872041-86-6]5-fluoropyridine-3-boronic acid</strong> (RENOTECH, 29.4g, 209mmol) were dissolved in a mixture of DME (1 .8L) and water (0.6L). Mixture was degassed with argon for 5min and [1 ,1 '-bis(diphenylphosphino)-ferrocene]dichloro- palladium(ll) (6.1 Og, 7.45mmol) was added. The resulting mixture was stirred at 65C for 1 .5h. 5-Fluoropyridin-3-yl)boronic acid (4.2g, 29.8mmol) and bis(diphenylphosphino)ferrocene]dichloro-palladium(ll) (0.6g, 0.74 mmol) were then added and the mixture stirred at 65C for 2h. 5-Fluoropyridin-3-yl)boronic acid (2.1 g, 14.9 mmol) and [1 ,1 '-bis(diphenylphosphino)ferrocene]dichloro-palladium(ll) (0.3g, 0.6 mmol) were again added and the mixture stirred at 65C for 1 h. The reaction mixture was cooled to room temperature and partitioned between DCM (1 .8L) and saturated NaHCC solution (0.9L). Phases were separated and the aqueous phase was back extracted with DCM (0.9L). The organic phases were combined and washed with water (0.6L). Phases were separated and the water phase was back extracted with DCM (0.4L). Organic layer were combined, dried over anhydrous Na2S04 and filtered. Active charcoal (60g) was added to this solution and it was stirred overnight. The solution was filtered to remove the active charcoal and solvent was evaporated. The residue was dissolved in DCM and it was filtered through silica amine pack and washed with more DCM. Solvent was evaporated and the product was triturated with 2-propanol and rinsed with 2-propanol to give ie f-butyl 4-(4-(6-(5-fluoropyridin-3- yl)pyrazin-2-yl)benzoyl)piperazine-1 -carboxylate (59.02g, 85% yield) as a white solid 1H NMR (400MHz, DMSO-d6) delta ppm: 9.44-9.33 (m, 3H); 8.76 (d, J= 2.53 Hz, 1 H); 8.63-8.55 (m, 1 H); 8.39 (d, J= 8.08 Hz, 2H); 7.61 (d, J= 8.34 Hz, 2H), 3.72-3.55 (m, 2H); 3.51 -3.26 (m, 6H); 1 .41 (s, 9H). [ES+MS] m/z 464 (M+H).

Reference： [1]Patent: WO2017/67881,2017,A1 .Location in patent: Page/Page column 16-17

45
[ 872041-86-6 ]
C₃H₂ClIN₂ [ No CAS ]
C₈H₄ClFIN₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%	With pyridine; oxygen; copper diacetate; In dichloromethane; at 20℃;	To a solution of 120 (100.0mg, 0.4mmoi) and 102 (1234ing, O8mmol) in DCM (iOOmL) was added pyridine (95mg, 1 2rnmol) and Cu(OAc)2 (218mg, 1 .2mmol), the mixture was stirred at room temperature under 02 balloon overnight. The reaction mixture was filtered and the filtrate was concentrated to dryness. The residue was purified by flashing chromatography column on silicon gel to afford product 131 (70.0mg, yield: 50%).?HNMR (400 MHz, CDC13): 7.76-7.84 (in, I H), 798 (s, 1 H), 846 (s, I H), 8.73 (s, I H).

Reference： [1]Patent: WO2017/117708,2017,A1 .Location in patent: Page/Page column 71; 72

46
[ 872041-86-6 ]
C₈H₁₁ClN₂Si [ No CAS ]
C₁₃H₁₃ClFN₃Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63.1%	With pyridine; oxygen; copper diacetate; In dichloromethane; at 20℃;	To a solution of 125 (?750mg, 0.38mmoI) and 102 (106.4mg. 0.75mmoi) in DCM (10.OmL) was added pyridine (90. 1mg, 1 i4rnrnol) and Cu(OAc)2 (2070mg, 1. i4mmoi), the mixture was stirred at room temperature under 02 balloon overnight. The reaction mixture was filtered and the filtrate was concentrated to dryness. The residue ?as purified by prep-TLC to afford product 132 (700mg, yield: 63.1%).LCMS: m/, 294.0 (M±H.

Reference： [1]Patent: WO2017/117708,2017,A1 .Location in patent: Page/Page column 72; 73

47
[ 872041-86-6 ]
[ 4522-35-4 ]
C₈H₅FIN₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84.82%	With pyridine; pyridine N-oxide; oxygen; copper diacetate; In dichloromethane; at 20℃; for 48h;	To a mixture of compound 180(30000mg, 1 5Smmol) and 102(32762mg, 232mmol) in DCM (2OrnL). was added pyridine (367.02mg, 4.64mmol), Cu(OAc)2(561.83mg, 3.O9mmoi) and i oxidopyridin-i--iurn (442.21 mg, 4.6Smmol, 3.OOEq) in one portion at room temperature. The mixture was stirred at room temperature for 48 hours under 02 protected. LCMS showed thereaction was completed. The mixture was filtrated and the filtrate was concentrated in reduced pressure. The residue was dissolved in ethyl acetate (4OmL). The organic phase was washed with water (3OmLx2), saturated brine (3OmLxi), dried over anhydrous Na2SO4, filtered and concentrated in vacuum. The residue was purified by silica gel chromatography to afford product 206(380.00mg. yield: 84.82%).LCM: m/z, 2899M+H).

Reference： [1]Patent: WO2017/117708,2017,A1 .Location in patent: Page/Page column 109

48
[ 872041-86-6 ]
[ 95095-84-4 ]
3-amino-6-(5-fluoro-3-pyridyl)pyridine-2-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
34%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In toluene; at 150℃; for 0.25h;Microwave irradiation;	To a microwave vial was added 3-amino-6-chloro-pyridine-2-carbonitrile (210 mg 1.37 mmol), <strong>[872041-86-6](5-fluoro-3-pyridyl)boronic acid</strong> (301 mg, 2.05 mmol).Potassium carbonate (756 mg, 5.47 mmol), Pd (PPh3) 4 (158 mg, 0.137 mmol) and toluene (5 mL).The reaction was then heated at 150 C for 15 minutes under microwave irradiation.The reaction mixture was filtered through EtOAc (EtOAc)EtOAc.The desired compound (101 mg, 34%) was obtained as pale yellow solid.
17%	With (chloro)phenylallyl[1,3?bis(2,6?bis(diphenylmethyl)?4?methylphenyl)imidazo?2?ylidene]palladium(II); potassium carbonate; In ethanol; at 80℃; for 1h;Inert atmosphere;	A mixture of 3-amino-6-chloro-pyridine-2-carbonitrile (330mg, 2.15mmol), 5- fluoropyridine-3-boronic acid (394mg, 2.69mmol), potassium carbonate (633mg, 4.73mmol) and [Pd(IPr*)(cin)Cl) (126mg, 0.1 1 mmol) in EtOH (9.9mL) was heated at 80C for 1 hour under an N2 atmosphere and then allowed to cool to room temperature. The mixture was filtered through celite and concentrated in vacuo. The resultant orange-brown gum was adsorbed onto silica and purified by flash chromatography on silica using an EtOAc/isohexane gradient as eluent to give the desired product (80mg, 17%) as a brown gum. 1H NMR (400MHz, CD3OD) delta 8.95 (d, 1 H), 8.43 (d, 1 H), 8.18-8.09 (m, 1 H), 7.93 (d, 1 H), 7.35 (d, 1 H)
17%	With C78H67ClN2Pd; potassium carbonate; In ethanol; at 80℃; for 1h;Inert atmosphere;	A mixture of 3-amino-6-chloro-pyridine-2-carbonitrile (330mg, 2.15mmol), 5- fluoropyridine-3-boronic acid (394mg, 2.69mmol), potassium carbonate (633mg, 4.73mmol) and [Pd(IPr*)(cin)CI) (126mg, 0.1 1 mmol) in EtOH (9.9 mL) was heated at 80C for 1 hour under an N2 atmosphere and then allowed to cool to room temperature. The mixture was filtered through celite and concentrated in vacuo. The resultant orange - brown gum was adsorbed onto silica and purified by flash chromatography on silica using an EtOAc/isohexane gradient as eluent to give the desired product (80mg, 17%) as a brown gum. 1H NMR (400MHz, CD3OD) delta 8.95 (d, 1 H), 8.43 (d, 1 H), 8.18-8.09 (m, 1 H), 7.93 (d, 1 H), 7.35 (d, 1 H)

Reference： [1]Patent: CN108779107,2018,A .Location in patent: Paragraph 0302-0304
[2]Patent: WO2017/162521,2017,A1 .Location in patent: Page/Page column 41; 42
[3]Patent: WO2017/162524,2017,A1 .Location in patent: Page/Page column 47; 48

49
[ 872041-86-6 ]
3,6-dichloro-2-(trifluoromethyl)pyridine [ No CAS ]
3-chloro-6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With xantphos PDG4; potassium carbonate; In ethanol; water; toluene; at 80℃; for 2.5h;Inert atmosphere;	A suspension of 3,6-dichloro-2-(trifluoromethyl)pyridine (2.0g, 9.26 mmol) and (5-fluoro- 3-pyridyl) boronic acid (1.44g, 10.19 mmol) in a mixture of EtOH (5.4 mL), toluene (20 mL) and water (9.25 mL) was sparged with N2 for 30 minutes at RT. K2CO3 (2.56g, 18.52 mmol) and Xantphos Pd G4 (222mg, 0.232 mmol) was added and the reaction heated to 80C for 2.5 hours. The reaction was allowed to cool to RT, diluted with EtOAc (100 mL) and washed with water (100 mL). The aqueous phase was extracted with further EtOAc (2 x 100 mL). The combined organic extracts were dried over MgS04 and evaporated to dryness under reduced pressure. The crude material was purified by flash chromatography on silica gel using an EtOAc/isohexane gradient as eluent to give the desired product (2.16g, 84%) as a pale orange oil which solidified on standing. 1H NMR (400MHz, CDCl3) delta 9.03 (s, 1 H), 8.58 (s, 1 H), 8.15 (d, 1 H), 7.98 (d, 1 H), 7.92 (d, 1 H).
84%	With methanesulfonato[9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene](2'-methylamino-1,1'-biphenyl-2-yl)palladium(ll); potassium carbonate; In water; toluene; at 80℃; for 2.5h;Inert atmosphere;	3,6-Dichloro-2-(trifluoromethyl)pyridine (2.0 g, 9.26 mmol) and <strong>[872041-86-6](5-fluoro-3-pyridyl)boronic acid</strong> (1.44 g, 10.19 mmol) at room temperatureAt EtOH (5.4 mL),A suspension of the mixture of toluene (20 mL) and water (9.25 mL) was sparged with N2 for 30 min.K2CO3 (2.56 g, 18.52 mmol) and Xantphos cyclopalladium complex fourth generation (222 mg, 0.232 mmol) were added and the reaction was heated to 80 C for 2.5 h. The reaction was cooled to room rt then diluted with EtOAc EtOAc. The aqueous phase was extracted with additional EtOAc (2×100 mL). The combined organic extracts were dried with MgSO4 and evaporated The crude material was purified by flash chromatography on silica gel eluting with EtOAc/EtOAc.The desired product (2.16 g, 84%) was obtained as a pale orange oil which was solidified.
75%	With 9-[5-(diphenylphosphanyl)-9,9-dimethyl-9H-xanthen-4-yl]diphenyl-lambda4-phosphanyl}-O-methanesulfonyl-8-methyl-8lambda4-aza-9-palladatricyclo[8.4.0.02,7]tetradeca-1(14),2,4,6,10,12-hexaene-9,9-bis(ylium)-10-uid-9-olate; potassium carbonate; In ethanol; water; toluene; at 80℃; for 2.5h;Inert atmosphere;	A mixture of 3,6-dichloro-2-(trifluoromethyl)pyridine (200mg, 0.94 mmol) and <strong>[872041-86-6](5-fluoro-3-pyridyl)boronic acid</strong> (144mg, 1 . 02 mmol) in ethanol (0.54mL), toluene (2mL) and H2O (0.93 mL) was sparged with N2 for 30 minutes. K2CO3 (256mg, 1 .85 mmol) and Xantphos palladacycle G4 (22mg, 0.023 mmol) were added and the reaction heated at 80C under an N2 atmosphere for 2 hours. The reaction was allowed to cool to RT, diluted with H2O (10 mL) and extracted with EtOAc (3 x 10 mL). The combined organic extracts were dried over MgSO4 and evaporated to dryness under reduced pressure to give a yellow oil. The crude product was purified by flash chromatography on silica gel using an EtOAc/isohexane gradient as eluent to give the desired product (0.192g, 75%) as a colourless oil that solidified on standing. 1H NMR (400 MHz, CDCI3) delta 9.03 (s, 1H), 8.58 (s, 1H), 8.15 (d, 1H), 7.98 (d, 1H), 7.92 (d, 1H).

Reference： [1]Patent: WO2017/162524,2017,A1 .Location in patent: Page/Page column 44; 45
[2]Patent: CN108779107,2018,A .Location in patent: Paragraph 0318-0320
[3]Patent: WO2017/162521,2017,A1 .Location in patent: Page/Page column 42; 43

50
[ 872041-86-6 ]
tert-butyl N-[6-chloro-2-(trifluoromethyl)-3-pyridyl]carbamate [ No CAS ]
tert-butyl N-[6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)-3-pyridyl]carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With 9-[5-(diphenylphosphanyl)-9,9-dimethyl-9H-xanthen-4-yl]diphenyl-lambda4-phosphanyl}-O-methanesulfonyl-8-methyl-8lambda4-aza-9-palladatricyclo[8.4.0.02,7]tetradeca-1(14),2,4,6,10,12-hexaene-9,9-bis(ylium)-10-uid-9-olate; potassium carbonate; In ethanol; water; toluene; for 3h;Reflux;	To a stirred suspension of <strong>[872041-86-6](5-fluoro-3-pyridyl)boronic acid</strong> (1 .7 g, 1 mmol), Xantphos palladacycle 4th generation (0.2g, 0.21 mmol) and tert-butyl N-[6-chloro-2-(trifluoromethyl)-3-pyridyl]carbamate (2.50g, 8.4mmol) in a mixture of ethanol (6.8mL) and toluene (25mL) was added K2CO3 (8.4mL of 2M in water, 17mmol). The reaction mixture was heated at reflux for 3hrs. The reaction mixture was cooled to room temperature and concentrated to dryness. The residue was adsorbed onto silica and purified by flash chromatography on silica using a gradient from 5-100% EtOAc/isohexane as eluent to give the desired compound (2.57g, 85%). 1 H NMR (400MHz, CDCI3) delta 9.02 (dd, 1 H), 8.79 (d, 1 H), 8.52 (d, 1 H), 8.12 (m, 1 H), 7.94 (d, 1 H), 7.01 (br.s, 1 H), 1.56 (s, 9H)
85%	With xantphos PDG4; potassium carbonate; In ethanol; water; toluene; for 3h;Reflux;	To a stirred suspension of <strong>[872041-86-6](5-fluoro-3-pyridyl)boronic acid</strong> (1 .70g, 12mmol), Xantphos palladacycle 4th generation (0.2g, 0.21 mmol) and tert-butyl N-[6-chloro-2- (trifluoromethyl)-3-pyridyl]carbamate (2.50g, 8.4mmol) in a mixture of ethanol (6.8ml_) and toluene (25ml_) was added K2CO3 (8.4ml_ of a 2M in water, 17mmol). The reaction mixture was heated at reflux for 3hrs. The reaction mixture was cooled to room temperature and concentrated to dryness. The residue was adsorbed onto silica and purified by flash chromatography on silica using a gradient from 5-100% EtOAc/isohexane as eluent to give the desired compound (2.57g, 85%). 1H NMR (400MHz, CDCI3) delta 9.02 (dd, 1 H), 8.79 (d, 1 H), 8.52 (d, 1 H), 8.12 (m, 1 H), 7.94 (d, 1 H), 7.01 (br.s, 1 H), 1.56 (s, 9H)
85%	With methanesulfonato[9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene](2'-methylamino-1,1'-biphenyl-2-yl)palladium(ll); potassium carbonate; In ethanol; toluene; for 3h;Reflux;	To <strong>[872041-86-6](5-fluoro-3-pyridyl)boronic acid</strong> (1.70 g, 12 mmol), Xantphos cyclopalladium complex 4th generation (0.2 g, 0.21 mmol)Stirring with a mixture of N-[6-chloro-2-(trifluoromethyl)-3-pyridyl]carbamic acid tert-butyl ester (2.50 g, 8.4 mmol) in ethanol (6.8 mL) and toluene (25 mL) K2CO3 (8.4 mL, 2M solution in water, 17 mmol) was added to the suspension. The reaction mixture was heated under reflux for 3 hours. The reaction mixture was cooled to room temperature and concentrated to dryness. The residue was adsorbed onto silica and purified by flash chromatography on silica using 5%-100%EtOAc/EtOAc gradient elutingTo give the desired compound (2.57 g, 85%).

Reference： [1]Patent: WO2017/162521,2017,A1 .Location in patent: Paragraph 35; 36
[2]Patent: WO2017/162524,2017,A1 .Location in patent: Page/Page column 33; 34
[3]Patent: CN108779107,2018,A .Location in patent: Paragraph 0259-0261

51
[ 872041-86-6 ]
[ 1427000-64-3 ]
4,5,6,7-tetrahydro-3-[2,6-bis(5-fluoro-3-pyridyl)phenyl]-2(3H)-benzothiazolethione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With palladium diacetate; cesium fluoride; johnphos; In tetrahydrofuran; at 60℃; for 8h;Inert atmosphere;	In a flask purged with nitrogen, synthesized in Reference Example 1 4, 5, 6, 7-tetrahydro-3-(2,6-dibromophenyl)-2 (3H) -benzothiazolthione, 210 mg of 5-fluoro-3-pyridylboronic acid, 5 g of tetrahydrofuran, 2-di-tert-butylphosphinobiphenyl 44 mg of cesium fluoride, 450 mg of cesium fluoride and 11 mg of palladium acetate. The obtained mixture was heated to 60 C. and stirred for 8 hours. To the obtained reaction solution were added 10 g of ethyl acetate and 20 g of water, and the layers were separated. The organic layer was separated again with 10 g of water, dried over magnesium sulfate, and the solvent was distilled off. The obtained residue was purified with a silica gel short column (adsorbed on 50 g of silica gel, eluted with 300 ml of chloroform), and the solvent was distilled off to obtain 180 mg of light yellow crystals. From the GC-MS, the obtained crystal was crystallized from 4,5,6,7-tetrahydro-3-[2,6-bis (5-fluoro-3-pyridyl)phenyl]-2(3H)-benzothiazolthione I confirmed that there was. Yield 83%

Reference： [1]Patent: JP6225984,2017,B2 .Location in patent: Paragraph 0073

52
[ 872041-86-6 ]
2-bromo-N-[(dimethylamino)methylidene]-5-nitrobenzenesulfonamide [ No CAS ]
2-(5-fluoropyridin-3-yl)-5-nitrobenzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With bis(triphenylphosphine)palladium(II) dichloride; potassium carbonate; triphenylphosphine; In propan-1-ol; water; at 120℃; under 3000.3 Torr; for 1h;	2-Bromo-N-[(dimethylamino)methylidene]-5-nitrobenzenesulfonamide (400 mg, 1 .19mmol) and <strong>[872041-86-6](5-fluoropyridin-3-yl)boronic acid</strong> (335 mg, 2.38 mmol) were dissolved in npropanol (110 ml, 1 .5 mol) and bis(triphenylphosphine)palladium(l I) dichloride (CAS13965-03-2) (41.9 mg, 59.5 pmol), triphenylphosphine (21.6 mg, 59.5 pmol) and aq. potassium carbonate solution (1 .8 ml, 2.0 M, 3.6 mmol) were added. The reaction was heated at 120C for 1 h (4 bar 40W).The reaction mixture was filtered over Celite and the solvent was removed under reduced pressure The crude was co-distilled with THF and used without further purification in the next step.

Reference： [1]Patent: WO2017/191000,2017,A1 .Location in patent: Page/Page column 427

53
[ 872041-86-6 ]
6-bromo-N-(1-methyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)picolinamide [ No CAS ]
5'-fluoro-N-(1-methyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)-[2,3'-bipyridine]-6-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 150℃; for 1h;Microwave irradiation;	Example 3 5'-fluoro-N-(1-methyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)-[2,3'-bipyridine]-6-carboxamide (I-3) A 1,4-dioxane (3 mL) solution of 6-bromo-N-(1-methyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)picolinamide (71.6 mg, 0.2 mmol), <strong>[872041-86-6](5-fluoropyridin-3-yl)boronic acid</strong> (42.3 mg, 0.3 mmol), Pd(PPh3)4(23.1 mg, 0.02 mmol), and 2M aqueous solution of Na2CO3 (0.3 mL, 0.6 mmol) was microwaved at 150 C. for 60 minutes. Solvent was removed in vacuo, and after silica gel chromatography; 5'-fluoro-N-(1-methyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)-[2,3'-bipyridine]-6-carboxamide was obtained as a light grey solid: 328.8 mg (88% yield); 1H NMR (300 MHz, DMSO-d6) delta 12.48 (s, 1H), 9.60 (s, 1H), 8.83-8.80 (m, 2H), 8.61 (ddd, J=9.9, 2.1, 2.1 Hz, 1H), 8.56 (s, 1H), 8.45 (dd, J=7.1, 1.6 Hz, 1H), 8.28-8.21 (m, 2H), 8.08 (d, J=7.9 Hz, 1H), 7.96 (td, J=7.9, 1.6 Hz, 1H), 7.46-7.42 (m, 1H), 3.99 (s, 4H); LRMS (M+H) m/z 375.62.

Reference： [1]Patent: US2018/111917,2018,A1 .Location in patent: Paragraph 0421-0422

54
[ 2103-94-8 ]
[ 872041-86-6 ]
4-(4-(5-fluoropyridin-3-yl)phenyl)thiazol-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; In 1,4-dioxane; ethanol; water; at 130℃; for 0.5h;Sealed tube;	General procedure: 4-(4-bromophenyl)thiazol-2-amine (1.0 mmol) was takenin water:Ethanol:1,4dioxane (6 mL) mixture in 1:1:5 ratio, potassium carbonate (3.0 mmol) and different boronic acids(1.1 mmol) were added to the reaction mixture and degassed with nitrogen gas for 15 min with stirring at RT. Bis(triphenylphosphine) palladium(II) dichloride (0.1 mmol) catalyst was added to the mixture and heated for 30 min at 130C in seal tube. The reaction mixture was filtered through celite, washed with methanol and filtrate was concentrated under reduced pressure, the resulting residue was dilutedwith ethylacetate and washed with water and brine solution.The organic layer was dried over anhydrous Na2SO4 andconcentrated under vacuo to give the crude product which was purified by column chromatography using hexane: ethylacetate as an eluent to get the title compounds (3a-n). It is noteworthy to mention that, in the presence of free aminogroup, coupling reaction underwent smoothly with desired products in good yields.

Reference： [1]Letters in Organic Chemistry,2018,vol. 15,p. 270 - 281

55
[ 872041-86-6 ]
ethyl 3-oxo-6-[6-(trifluoromethyl)pyridin-3-yl]-2,3-dihydropyridazine-4-carboxylate [ No CAS ]
ethyl 2-(5-fluoropyridin-3-yl)-3-oxo-6-[6-(trifluoromethyl)pyridin-3-yl]-2,3-dihydropyridazine-4-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With pyridine; copper diacetate; triethylamine; In acetonitrile; at 80℃; for 3h;	Ethyl 3-oxo-6-[6-(trifluoromethyl)pyrid in-3-yl]-2,3-d ihyd ropyridazine-4-carboxylate (5 g, 15.96 mmol) was dissolved in acetonitrile (141 mL) followed by the addition of <strong>[872041-86-6](5-fluoropyridin-3-yl)boronic acid</strong> (3.37 g, 23.94 mmol), triethylamine (4.45 mL, 31.9 mmol), pyridine (2.58 mL,31.9 mmol) and anhydrous copper diacetate (7.25 g, 39.9 mmol). The reaction mixture was stirred for 3 h at 80C followed by the addition of water. The solution was adjusted to pH 3 by adding 1 M aqueous hydrochloric acid followed by extraction with ethyl acetate three times. The combined organic phases were washed with brine, dried over sodium sulfate, filtrated andconcentrated to receive 5.6 g (86%) of the title compound.LC-MS (Instrument: Waters Acquity UPLC-MS SQD 3001; column: Acquity UPLC BEH 0181.7 50x2.lmm; eluent A: Water + 0.lvol% formic acid (99%) eluent B: acetonitrile; gradient: 0-1 .6 mm 1-99% B, 1.6-2.0 mm 99% B; flow 0.8 mL/min; temperature: 60C; injection: 2 pL; DADscan: 210-400 nm; ELSD): R1 = 1.15 mm; MS (ESIpos): mlz = 409.2 [M+H]

Reference： [1]Patent: WO2018/146010,2018,A1 .Location in patent: Page/Page column 139

56
[ 872041-86-6 ]
2-chloro-N-[2-(1H-indol-3-yl)ethyl]-7-isopropenylthieno[3,2-d]pyrimidin-4-amine [ No CAS ]
N-(2-(1H-indol-3-yl)ethyl)-2-(5-fluoropyridin-3-yl)-7-(prop-1-en-2-yl)thieno[3,2-d]pyrimidin-4-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74.49%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 110℃; for 0.5h;Microwave irradiation; Sealed tube; Inert atmosphere;	2- Chloro-N-[2-(lH ndol-3-yl)ethyl]-7-isopropenyl-thieno[3,2-d]pyrimidin-4-amine (95 mg, 252.38 umol, 1 eq), <strong>[872041-86-6](5-fluoro-3-pyridyl)boronic acid</strong> (53.34 mg, 378.58 umol, 1.5 eq), Pd(dppf)Cl2 (18.47 mg, 25.24 umol, 0.1 eq) and Cs2C03 (246.69 mg, 757.15 umol, 3 eq) in 1,4-dioxane (2 mL) and H20 (0.5 mL) were taken up into a microwave tube. The sealed tube was purged with N2 for 3 min then heated at 110 C for 30 min under microwave. LC-MS showed most of starting material was consumed and 85% of desired compound was detected. The reaction mixture was concentrated under reduced pressure to give a residue which was purified on silica gel column chromatography (from PE/EtOAc = 1/0 to 10/3, TLC: PE/EtOAc = 3/1, Rf = 0.44) to give the product 2-(5-fluoro- (0864) 3- pyridyl)-N-[2-(lH-indol-3-yl)ethyl]-7-isopropenyl-thieno[3,2-d]pyrimidin-4-amine (85 mg, 188.00 umol, 74.49% yield, 95% purity) as oil. NMR (400 MHz, CDCb) delta ppm 9.59 (s, 1H), 8.55 (d, J = 2.6 Hz, 1H), 8.48 (d, J = 10.1 Hz, 1H), 8.07 (s, 1H), 7.69 (d, J = 7.9 Hz, 1H), 7.56 (s, 1H), 7.42 (d, J = 7.9 Hz, 1H), 7.26-7.22 (m, 1H), 7.20-7.15 (m, 1H), 7.11 (s, 1H), 6.70 (s, 1H), 5.46 (s, 1H), 5.06 (s, 1H), 4.14 (q, J = 6.5 Hz, 2H), 3.26 (t, J = 6.5 Hz, 2H), 2.30 (s, 3H); ES- LCMS m/z 430.0 [M+H]+.

Reference： [1]Patent: WO2018/195397,2018,A2 .Location in patent: Paragraph 00245

57
[ 872041-86-6 ]
N-(2-(1H-indol-3-yl)ethyl)-2-chloro-7-(prop-1-en-2-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine [ No CAS ]
N-(2-(1H-indol-3-yl)ethyl)-2-(5-fluoropyridin-3-yl)-7-(prop-1-en-2-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53.2%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 110℃; for 0.5h;Microwave irradiation;	To a solution of 2-chloro-N-[2-(lH-indol-3-yl)ethyl]-7-isopropenyl-pyrrolo[2,l-f][l,2,4]triazin-4- amine (65 mg, 144.10 umol, 1 eq) in 1,4-dioxane (3 mL) and H20 (1 mL) was added (5-fluoro-3- pyridyl)boronic acid (30.46 mg, 216.15 umol, 1.5 eq), Pd(dppf)Cl2 (15.82 mg, 21.62 umol, 0.15 eq) and CS2CO3 (140.85 mg, 432.31 umol, 3.0 eq). The mixture was stirred at 110 C under microwave for 0.5 h. LCMS showed about 72% of desired product was detected. The reaction mixture was filtered and the filtrate was diluted with H2O (15 mL) then extracted with EtOAc (15 mL x 3). The combined organic layers were dried over Na2SO4;, filtered and concentrated under reduced pressure to give a residue which was purified by preparative TLC (PE/EtOAc = 1.5/1, Rf = 0.6) to give 2-(5-fluoro-3-pyridyl)-N-[2-(lH-indol-3-yl)ethyl]-7-isopropenyl-pyrrolo[2,l- f][l,2,4]triazin-4-amine (40 mg, 76.61 umol, 53.2% yield) as a yellow solid. NMR (400 MHz, CDCl3) delta ppm 9.29 (s, 1H), 8.38 (d, J= 2.9 Hz, 1H), 8.23-8.16 (m, 1H), 8.05 (br s, 1H), 7.55 (d, J = 7.7 Hz, 1H), 7.30-7.27 (m, 1H), 7.30-7.24 (m, 1H), 7.14-7.09 (m, 1H), 7.07-7.02 (m, 1H), 6.95 (d, J = 2.2 Hz, 1H), 6.54 (d, J = 4.6 Hz, 1H), 6.34-6.23 (m, 2H), 5.45 (t, J = 5.6 Hz, 1H), 5.27 (s, 1H), 3.95 (q, J= 6.5 Hz, 2H), 3.09 (t, J=6.6 Hz, 2H), 2.15 (s, 3H); ES-LCMS m/z 413.1 [M+H].

Reference： [1]Patent: WO2018/195397,2018,A2 .Location in patent: Paragraph 00267

58
[ 872041-86-6 ]
[ 1266105-16-1 ]
4,6-dichloro-2-(5-fluoro-3-pyridyl)pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
37.8%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 80℃; for 0.5h;Microwave irradiation; Sealed tube;	4,6-Dichloro-2-iodo-pyrimidine (500 mg, 1.79 mmol, 1 eq), <strong>[872041-86-6](5-fluoro-3-pyridyl)boronic acid</strong> (251.96 mg, 1.79 mmol, 1 eq), Na2CO3 (568.55 mg, 5.36 mmol, 3.0 eq) and Pd(dppf)Cl2 (130.84 mg, 178.81 umol, 0.1 eq) in 1,4-dioxane (6 mL) and water (1.2 mL) were taken up into a microwave tube. The sealed tube was heated at 80 C for 30 min under microwave. LCMS showed 53% of desired compound was detected. The reaction mixture was diluted with EtOAc (30 mL) and filtered through a pad of celite. The filtrate was concentrated under reduced pressure to give a residue which was purified by flash silica gel chromatography (from PE/EtOAc = 100/1 to 10/3, TLC: PE/EtOAc = 3/1, Rf = 0.80) to yield 4,6-dichloro-2-(5-fluoro-3-pyridyl)pyrimidine (165 mg, 676.08 umol, 37.8% yield, 100% purity) as a white solid. NMR (400 MHz, CD3OD) delta ppm 9.36 (s, 1H), 8.67 (d, J= 2.9 Hz, 1H), 8.52-8.44 (m, 1H), 7.76 (s, 1H); ES-LCMS m/z 243.9, 245.9 [M+H]

Reference： [1]Patent: WO2018/195397,2018,A2 .Location in patent: Paragraph 00277

59
[ 872041-86-6 ]
2-chloro-9-isopropyl-N-(2-(1-methyl-1H-indol-3-yl)ethyl)-9H-purin-6-amine [ No CAS ]
2-(5-fluoropyridin-3-yl)-9-isopropyl-N-(2-(1-methyl-1H-indol-3-yl)ethyl)-9H-purin-6-amine hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
36.8%		2-Chloro-9-isopropyl-N-[2-(l-methylindol-3-yl)ethyl]purin-6-amine (100 mg, 271.10 umol, 1 eq), <strong>[872041-86-6](5-fluoro-3-pyridyl)boronic acid</strong> (95.50 mg, 677.76 umol, 2.5 eq), Pd(dppf)Cl2; (19.84 mg, 27.11 umol, 0.1 eq) and Cs2CO3 (264.99 mg, 813.31 umol, 3.0 eq) were taken up into a microwave tube in 1,4-dioxane (3 mL) and H20 (0.6 mL). The sealed tube was heated at 120 C for 30 min under microwave. LC-MS showed the start material was consumed completely and one main peak with desired MS was detected. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in EtOAc (50 mL), filtered through Si02. The cake was rinsed with EtOAc (10 mL x 2). The combined organic layers were concentrated under reduced pressure to give a residue which was purified by preparative HPLC (column: Phenomenex Gemini 15025mm 10um; mobile phase: [water (0.05% HC1)-ACN]; B%: 55%-85%, lOmin). The desired fraction was lyophilized to yield 2-(5-fluoro-3-pyridyl)-9-isopropyl-N-[2-(l-methylindol-3- yl)ethyl]purin-6-amine (53.81 mg, 36.8% yield, 100% purity, 3HC1 salt) as a yellow solid. MR (400 MHz, CD3OD) delta ppm 9.36 (s, 1H), 9.11 (br s, 1H), 8.84 (s, 1H), 8.75 (d, J = 8.8 Hz, 1H), 7.60 (d, J= 7.9 Hz, 1H), 7.20 (d, J= 7.9 Hz, 1H), 7.07 (t, J= 7.5 Hz, 1H), 7.02-6.93 (m, 2H), 5.09 (td, J= 6.8, 13.6 Hz, 1H), 4.16-4.10 (m, 2H), 3.61 (s, 3H), 3.20 (t, J= 6.6 Hz, 2H), 1.72 (d, J = 6.8 Hz, 6H); ES-LCMS m/z 430.2 [M+H].

Reference： [1]Patent: WO2018/195397,2018,A2 .Location in patent: Paragraph 00308; 00313

60
[ 872041-86-6 ]
(3R)-N-(6-chloro-3-isopropylimidazo[1,2-a]pyrazin-8-yl)-2,3,4,9-tetrahydro-1H-carbazol-3-amine [ No CAS ]
(3R)-N-[6-(5-fluoro-3-pyridyl)-3-isopropylimidazo[1,2-a]pyrazin-8-yl]-2,3,4,9-tetrahydro-1H-carbazol-3-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38.4%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 110℃; for 0.5h;Microwave irradiation; Sealed tube; Inert atmosphere;	To a solution of (3R)-N-(6-chloro-3-isopropyl-imidazo[1,2-a]pyrazin-8-yl)-2,3,4,9-tetrahydro- 1H-carbazol-3 -amine (60 mg, 157.94 mupiiotaomicron, 1 eq) and <strong>[872041-86-6](5-fluoro-3-pyridyl)boronic acid</strong> (44.51 mg, 315.89 muiotaetaomicron, 2.0 eq) in 1,4-dioxane (2 mL) and H2O (0.5 mL) was added Pd(dppf)Cl2 (11.56 mg, 15.79 mupiiotaomicron, 0.1 eq) and Cs2CO3 (154.38 mg, 473.83 mupiiotaomicron, 3.0 eq). The sealed tube was purged with N2 for 3 min and heated at 110 C for 0.5 h under microwave. The reaction mixture was filtered and concentrated under reduced pressure to give a residue which was purified by preparative HPLC twice (column: Phenomenex Gemini 15025mm10um; mobile phase: [water(0.05%HCl)-ACN]; B%: 40%-70%, lOmin; column: Gemini 150*25 5u; mobile phase: [water (0.05% ammonia hydroxide v/v)-ACN]; B%: 50%-80%, 10 min), followed by lyophilization to yield compound (3R)-N-[6-(5-fluoro-3-pyridyl)-3-isopropyl-imidazo[1,2- a]pyrazin-8-yl] -2,3, 4,9-tetrahydro-lH-carbazol-3 -amine (26.85 mg, 60.59 mupiiotaomicron, 38.4% yield, 99.4% purity) as a white solid. NMR (400 MHz, CD3OD) delta ppm 9.07 (s, 1H), 8.38 (d, J = 2.6 Hz, 1H), 8.25 (td, J = 2.2, 10.2 Hz, 1H), 8.19 (s, 1H), 7.34 (d, J = 7.7 Hz, 1H), 7.28-7.23 (m, 2H), 7.04-6.97 (m, 1H), 6.96-6.89 (m, 1H), 4.82-4.74 (m, 1H), 4.59 (s, 1H), 3.39-3.31 (m, 1H), 3.27- 3.21 (m, 1H), 2.93 (t, J = 6.2 Hz, 2H), 2.83 (dd, J = 7.2, 15.1Hz, 1H), 2.35 (dt, J = 2.5, 6.4 Hz, 1H), 2.25-2.13 (m, 1H), 1.38 (dd, J = 2.3, 6.7 Hz, 6H); ES-LCMS m/z 441.3 [M+H].

Reference： [1]Patent: WO2018/195397,2018,A2 .Location in patent: Paragraph 00377; 00379

61
[ 872041-86-6 ]
6-chloro-N-[2-(1H-indol-3-yl)ethyl]-3-isopropylimidazo[1,2-a]pyrazin-8-amine [ No CAS ]
6-(5-fluoro-3-pyridyl)-N-[2-(1H-indol-3-yl)ethyl]-3-isopropylimidazo[1,2-a]pyrazin-8-amine hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57.8%		6-Chloro-N-[2-(lH-indol-3-yl)ethyl]-3-isopropyl-imidazo[l,2-a]pyrazin-8-amine (60 mg, 162.78 muiotaetaomicron, 1 eq), <strong>[872041-86-6](5-fluoro-3-pyridyl)boronic acid</strong> (45.87 mg, 325.56 muiotaetaomicron, 2.0 eq), Pd(dppf)Cl2 (11.91 mg, 16.28 muetaiotaomicron, 0.1 eq) and Cs2C03 (159.11 mg, 488.35 muiotaetaomicron, 3.0 eq) were taken up into a microwave tube in 1,4-dioxane (2 mL) and H20 (0.5 mL). The mixture was purged with N2 for 3 min. The sealed tube was heated at 110 C for 30 min under microwave. The reaction mixture was diluted with (20 mL) and extracted with ethyl acetate (20 mL x 3). The combined organic layers were dried over anhydrous Na2S04, filtered and concentrated under reduced pressure to give a residue which was purified by preparative HPLC (column: Phenomenex Synergi CI 8 15030mm4um; mobile phase: [water(0.05%HCl)-ACN]; B%: 30%-60%, 12min), followed by lyophilization to yield 6-(5-fluoro-3-pyridyl)-N-[2-(lH-indol-3-yl)ethyl]-3-isopropyl- imidazo[l,2-a]pyrazin-8-amine (50.13 mg, 94.00 muiotaetaomicron, 57.8% yield, 98.2% purity, 3HC1) as a yellow solid. MR (400 MHz, CD3OD) delta ppm 9.21 (br s, 1H), 8.86 (br s, 1H), 8.74 (d, J = 9.0 Hz, 1H), 8.57 (s, lH), 7.89 (s, 1H), 7.51 (d, J = 7.8 Hz, 1H), 7.18 (d, J = 8.3 Hz, 1H), 7.09 (s, 1H), 6.94 (t, J = 7.5 Hz, 1H), 6.89-6.81 (m, 1H), 4.06 (t, J = 6.1Hz, 2H), 3.46 (d, J = 6.0 Hz, 1H), 3.18 (t, J = 6.3 Hz, 2H), 1.42 (d, J = 6.3 Hz, 6H); ES-LCMS m/z 415.3 [M+H]+.

Reference： [1]Patent: WO2018/195397,2018,A2 .Location in patent: Paragraph 00698; 00705

62
[ 872041-86-6 ]
N-(2-(1H-indol-3-yl)ethyl)-2-chlorothieno[2,3-d]pyrimidin-4-amine [ No CAS ]
N-(2-(1H-indol-3-yl)ethyl)-2-(5-fluoropyridin-3-yl)thieno[2,3-d]pyrimidin-4-amine hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
36.59%		[00235] Step 2: N-(2-(1H-indol-3-yl)ethyl)-2-(5-fluoropyridin-3-yl)thieno [2,3- d]pyrimidin-4-amine (I-5) To a solution of 2-chloro-N-[2-(lH-indol-3-yl)ethyl]thieno[2,3-d]pyrimidin-4-amine (100 mg, 298.04 umol, 1 eq) in 1,4-dioxane (3 mL) and H20 (1 mL) was added <strong>[872041-86-6](5-fluoro-3-pyridyl)boronic acid</strong> (75.59 mg, 536.47 umol, 1.8 eq), Cs2C03 (291.32 mg, 894.11 umol, 3.0 eq) and Pd(dppf)Cl2 (32.71 mg, 44.71 umol, 0.15 eq). The mixture was stirred at 120 C under microwave for 1 h. LC-MS showed the starting material was consumed completely and one main peak with desired MS was detected. The reaction mixture was filtered. The filtrate was diluted with H20 (15 mL) and extracted with EtOAc (15 mL x 3). The combined organic layers were dried over Na2S04, filtered and concentrated under reduced pressure to give a residue which was purified by preparative HPLC (HC1 condition; column: Phenomenex Kinetex XB-C18 150mm*30mm, 5 mupiiota; mobile phase: [water(0.05%HCl)-ACN];B%: 50%-75%,12min) and the desired fraction was lyophilized to yield 2-(5-fluoro-3-pyridyl)-iV-[2-(lH-indol-3-yl)ethyl]thieno[2,3-d]pyrimidin-4-amine (54.40 mg, 109.05 umol, 36.59% yield, 100% purity, 3HC1 salt) as a yellow solid. MR (400 MHz, CD3OD) delta ppm 9.19 (s, 1H), 8.84 (s, 1H), 8.58 (d, J = 9.3 Hz, 1H), 7.63-7.57 (m, 2H), 7.54 (d, J = 5.7 Hz, 1H), 7.19 (d, J = 7.7 Hz, 1H), 7.02-6.90 (m, 3H), 4.08 (t, J = 6.8 Hz, 2H), 3.19 (t, J = 6.7 Hz, 2H); ES-LCMS m/z 390.0 [M+H]

Reference： [1]Patent: WO2018/195397,2018,A2 .Location in patent: Paragraph 00235

63
[ 939979-43-8 ]
[ 872041-86-6 ]
5-chloro-7-(5-fluoro-3-pyridyl)-3-methylpyrazolo[1,5-a]pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52.7%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 110.0℃; for 1.0h;Microwave irradiation; Sealed tube;	5,7-Dichloro-3-methyl-pyrazolo[l,5-a]pyrimidine (190 mg, 938.52 mupiiotaomicron, 1 eq), (5-fluoro-3- pyridyl)boronic acid (138.86 mg, 985.45 muiotaetaomicron, 1.05 eq), Pd(dppf)Cl2 (68.67 mg, 93.85 muiotaetaomicron, 0.1 eq) and Cs2C03 (611.58 mg, 1.88 mmol, 2 eq) were taken up into a microwave tube in 1,4-dioxane (3 mL) and H20 (1 mL). The sealed tube was heated at 110 C for 1 h under microwave. The mixture was concentrated and water (10 mL) was added. The mixture was extracted with EtOAc (20 mL x 3). The combined organic layers were dried over Na2S04, filtered and concentrated to yield a residue which was purified on silica gel column chromatography (from PE/EtOAc = 1/0 to 10/3, TLC: PE/EtOAc = 3/1, Rf = 0.50) to yield 5-chloro-7-(5-fluoro-3-pyridyl)-3-methyl- pyrazolo[l,5-a]pyrimidine (130 mg, 494.92 mupiiotaomicron, 52.7% yield, 100.0%) purity) as a yellow solid. NMR (400 MHz, CDC13) delta ppm 8.97 (s, 1H), 8.69 (d, J = 2.7 Hz, 1H), 8.38-8.31 (m, 1H), 8.04 (s, 1H), 6.92 (s, 1H), 2.40 (s, 3H); ES-LCMS m/z 263.0, 265.0 [M+H]+.

Reference： [1]Patent: WO2018/195397,2018,A2 .Location in patent: Paragraph 00747; 00750

64
[ 872041-86-6 ]
(3R)-N-(2-chloropyrido[3,2-d]pyrimidin-4-yl)-2,3,4,9-tetrahydro-1H-carbazol-3-amine [ No CAS ]
(3R)-N-[2-(5-fluoro-3-pyridyl)pyrido[3,2-d]pyrimidin-4-yl]-2,3,4,9-tetrahydro-1H-carbazol-3-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55.5%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 110℃; for 0.5h;Microwave irradiation; Sealed tube;	(3R)-N-(2-chloropyrido[3,2-d]pyrimidin-4-yl)-2,3,4,9-tetrahydro-lH-carbazol-3-amine (60 mg, 171.52 muiotaetaomicron, 1 eq), <strong>[872041-86-6](5-fluoro-3-pyridyl)boronic acid</strong> (29.00 mg, 205.82 muiotaetaomicron, 1.2 eq), Pd(dppf)Cl2 (12.55 mg, 17.15 mupiiotaomicron, 0.1 eq) and Cs2C03 (167.65 mg, 514.56 mupiiotaomicron, 3 eq) were taken up into a microwave tube in 1,4-dioxane (2 mL) and H20 (0.5 mL). The sealed tube was heated at 110 C for 0.5 h under microwave. The reaction mixture was diluted with water (5 mL) and extracted with EtOAc (10 mL x 3). The combined organic layers were dried over Na2S04, filtered and concentrated under reduced pressure to give a residue which was purified by preparative HPLC (column: Agela ASB 15025mm5um;mobile phase: [water(0.05%HCl)-ACN];B%: 55%-85%, 8 min), followed by lyophilization to yield (3R)-N-[2-(5-fluoro-3-pyridyl)pyrido[3,2-d]pyrimidin-4- yl]-2,3,4,9-tetrahydro-lH-carbazol-3-amine (39.09 mg, 95.24 muiotaetaomicron, 55.5% yield, 100.0% purity, OR: [a]23 6D = 0.471 (MeOH, c = 0.110 g/100 mL).) as a yellow solid. NMR (400 MHz, CD3OD) delta ppm 9.32 (s, 1H), 9.01 (dd, J = 1.2, 4.4 Hz, 1H), 8.83 (d, J = 2.4 Hz, 1H), 8.61-8.49 (m, 1H), 8.32 (dd, J = 1.2, 8.6 Hz, 1H), 8.04 (dd, J = 4.4, 8.6 Hz, 1H), 7.33 (d, J = 7.6 Hz, 1H), 7.25 (d, J = 8.1Hz, 1H), 6.98 (t, J = 7.5 Hz, 1H), 6.91-6.81 (m, 1H), 5.22-5.04 (m, 1H), 3.28 (s, 1H), 3.12-2.86 (m, 3H), 2.43-2.27 (m, 2H); ES-LCMS m/z 411.2 [M+H]+.

Reference： [1]Patent: WO2018/195397,2018,A2 .Location in patent: Paragraph 00759; 00761

65
[ 872041-86-6 ]
(3R)-N-(2-chloroimidazo[2,1-f][1,2,4]triazin-4-yl)-2,3,4,9-tetrahydro-1H-carbazol-3-amine [ No CAS ]
(3R)-N-[2-(5-fluoro-3-pyridyl)imidazo[2,1-f][1,2,4]triazin-4-yl]-2,3,4,9-tetrahydro-1H-carbazol-3-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52.8%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 110℃; for 2h;Inert atmosphere;	A mixture of (3R)-N-(2-chloroimidazo[2, l-f][l,2,4]triazin-4-yl)-2,3,4,9-tetrahydro-lH-carbazol- 3-amine (100 mg, 289.26 muiotaetaomicron, 1 eq), <strong>[872041-86-6](5-fluoro-3-pyridyl)boronic acid</strong> (81.52 mg, 578.52 muiotaetaomicron, 2 eq), Cs2C03 (282.74 mg, 867.78 muiotaetaomicron, 3 eq) and Pd(dppf)Cl2 (21.17 mg, 28.93 muiotaetaomicron, 0.1 eq) in 1,4-dioxane (2 mL) and H20 (0.5 mL) was stirred at 110 C for 2 h under N2 atmosphere. After filtration, the filtrate was concentrated. The residue was purified by preparative TLC (PE/EtOAc = 1/1, Rf = 0.3) to yield (3R)-N-[2-(5-fluoro-3-pyridyl)imidazo[2,l-f][l,2,4]triazin-4-yl]-2,3,4,9- tetrahydro-lH-carbazol-3 -amine (60.97 mg, 152.65 muiotaetaomicron, 52.8% yield, 100% purity, [a]26 9D = + 9.272 (MeOH, c = 0.101 g/100 mL)) as a yellow solid. MR (400 MHz, CD3OD) delta ppm 9.30 (s, 1H), 8.54 (d, J = 2.7 Hz, 1H), 8.42 (td, J = 2.1, 9.8 Hz, 1H), 7.96 (d, J = 1.0 Hz, 1H), 7.55 (s, 1H), 7.36 (d, J = 7.6 Hz, 1H), 7.25 (d, J = 8.1Hz, 1H), 7.05-6.97 (m, 1H), 6.96-6.89 (m, 1H), 4.98-4.90 (m, 1H), 3.26 (br s, 1H), 2.97 (t, J = 5.7 Hz, 2H), 2.90 (dd, J = 7.2, 15.3 Hz, 1H), 2.40- 2.32 (m, 1H), 2.31-2.21 (m, 1H); ES-LCMS m/z 399.9 [M+H]+.

Reference： [1]Patent: WO2018/195397,2018,A2 .Location in patent: Paragraph 001094; 001100

66
[ 872041-86-6 ]
N-[6-chloro-2-(trifluoromethyl)-3-pyridyl]carbamic acid isopropyl ester [ No CAS ]
N-[6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)-3-pyridyl]carbamic acid isopropyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
37%	With (chloro)phenylallyl[1,3?bis(2,6?bis(diphenylmethyl)?4?methylphenyl)imidazo?2?ylidene]palladium(II); In ethyl acetate; at 80℃; for 2h;	To N-[6-chloro-2-(trifluoromethyl)-3-pyridyl]carbamic acid isopropyl ester (100 mg, 0.35 mmol), <strong>[872041-86-6](5-fluoro-3-pyridyl)boronic acid</strong> (75 mg, 0.53 mmol And a suspension of [Pd(IPr*)(cin)Cl) (20 mg, 0.018 mmol) in EtOAc (3 mL). The mixture was then heated to 80 C for 2 hours.The mixture was filtered and concentrated in vacuo to celite. Purification by flash chromatography on silica using a 20% EtOAc / EtOAc gradient eluting elute To carry out the second round of purification,The desired compound (45 mg, 37%) was obtained as a white solid.

Reference： [1]Patent: CN108779107,2018,A .Location in patent: Paragraph 0291-0293

67
[ 872041-86-6 ]
[ 1532-24-7 ]
methyl 3-chloro-6-(5-fluoro-3-pyridyl)pyridine-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	With methanesulfonato[9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene](2'-methylamino-1,1'-biphenyl-2-yl)palladium(ll); potassium carbonate; In ethanol; water; at 85℃; for 2h;Inert atmosphere;	A solution of methyl 3,6-dichloropyridine-2-carboxylate (1.00 g, 4.85 mmol) and <strong>[872041-86-6](5-fluoro-3-pyridyl)boronic acid</strong> (0.752 g, 5.34 mmol) in ethanol (2.7 mL) 10.0 mL) and water (4.6 mL) were sparged with N2 for 30 minutes at room temperature.Then K2CO3 (1.342 g, 9.71 mmol) and Xantphos cyclopalladium G4 (0.117 g, 0.121 mmol) were added, and the yellow solution was heated to 85 C under N2 atmosphere for 2 h.The reaction was cooled to room temperature and diluted with EtOAc EtOAcIt was washed with water (50 mL).The aqueous phase was further extracted with EtOAc (2×50 mL). The combined organic extracts were dried with MgSO 4 The crude material was flash chromatographed on silica gel using EtOAc / isohexane gradient as eluentPurify to give the desired product (0.94 g, 73%).

Reference： [1]Patent: CN108779107,2018,A .Location in patent: Paragraph 0328-0330

68
[ 53976-62-8 ]
[ 872041-86-6 ]
5-chloro-2-(5-fluoro-3-pyridyl)-1-oxido-pyridin-1-ium [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	With methanesulfonato[9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene](2'-methylamino-1,1'-biphenyl-2-yl)palladium(ll); potassium carbonate; In ethanol; water; toluene; at 85℃; for 22h;Inert atmosphere;	2,5-dichloro-1-oxido-pyridin-1-ium (0.25 g, 1.52 mmol)And <strong>[872041-86-6](5-fluoro-3-pyridyl)boronic acid</strong> (0.258 g, 1.83 mmol) in EtOH (0.675 mL),A mixture of toluene (2.5 mL) and water (1.15 mL) was sparged with N2 at room temperature for 30 min.Then K2CO3 (0.421 g, 3.05 mmol) and Xantphos cyclopalladium G4 (37 mg, 0.0381 mmol) were added.The yellow solution was heated to 85 C under N2 atmosphere for 22 h.The reaction was cooled to rt (EtOAc) (150 mL)Dilute in medium and wash with water (100 mL).The aqueous phase was further extracted with EtOAc (2×100 mL).The combined organic extracts were dried over MgSO4.And evaporated to dryness under reduced pressure.The crude product was passed through EtOAc /The isohexane gradient was purified by flash chromatography on silica gel as an eluent.The desired product (0.21 g, 61%) was obtained as a colourless solid

Reference： [1]Patent: CN108779107,2018,A .Location in patent: Paragraph 0346-0348

69
[ 872041-86-6 ]
5-bromo-3-(prop-1-en-2-yl)pyrazin-2-amine [ No CAS ]
5-(5-fluoro-3-pyridyl)-3-isopropenyl-pyrazin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; for 3h;Reflux;	2-Amino-3-(prop-2-enyl)-5-bromopyrazine (428mg, 2.00mmol), (5-fluoro-3- pyridyl)boronic acid (41 1 mg, 2.80mmol) and cesium carbonate (1 .63g, 5.00mmol) were dissolved in a mixture of 1 ,4-dioxane (4.5ml) and water (1 ml), and [1 ,1 - bis(diphenylphosphino)ferrocene]-dichloropalladium(ll) (85mg, 0.1 1 mmol) was added. T he resulting mixture was heated under reflux for 3 hours, then allowed to cool, diluted with ethyl acetate (100ml), and then washed with brine. The resulting organic solution was dried over magnesium sulfate then filtered and concentrated under reduced pressure to give 2 a dark yellow liquid which began to crystallize. This was purified by chromatography on silica gel using a gradient of ethyl acetate in isohexane as eluent to give the title compound (400mgs, 86%) as a yellow solid. 1H NMR (400 MHz, CDCI3) delta 8.95 (s, 1 H), 8.45 (d, 1 H), 8.40 (s, 1 H), 8.00 (dd, 1 H), 5.60 (s, 1 H), 5.55 (s, 1 H) 5.10 (br s, 2H), 2.25 (s, 3H).
86%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; for 3h;Reflux;	2-Amino-3-(prop-2-enyl)-5-bromopyrazine (428mg, 2.00mmol), (5-fluoro-3- pyridyl)boronic acid (41 1 mg, 2.80mmol) and cesium carbonate (1 .63g, 5.00mmol) were dissolved in a mixture of 1 ,4-dioxane (4.5ml) and water (1 ml), and [1 ,1 - bis(diphenylphosphino)ferrocene]-dichloropalladium(ll) (85mg, 0.1 1 mmol) was added. T he resulting mixture was heated under reflux for 3 hours, then allowed to cool, diluted with ethyl acetate (100ml), and then washed with brine. The resulting organic solution was dried over magnesium sulfate then filtered and concentrated under reduced pressure to give 2 a dark yellow liquid which began to crystallize. This was purified by chromatography on silica gel using a gradient of ethyl acetate in isohexane as eluent to give the title compound (400mgs, 86%) as a yellow solid. 1H NMR (400 MHz, CDCI3) delta 8.95 (s, 1 H), 8.45 (d, 1 H), 8.40 (s, 1 H), 8.00 (dd, 1 H), 5.60 (s, 1 H), 5.55 (s, 11-1) 5.10 (br s, 2H), 2.25 (s, 3H).

Reference： [1]Patent: WO2019/57723,2019,A1 .Location in patent: Page/Page column 30-31
[2]Patent: WO2019/57725,2019,A1 .Location in patent: Page/Page column 35-36

70
[ 872041-86-6 ]
5-chloro-2-methylsulfanyl-4-(trifluoromethyl)pyrimidine [ No CAS ]
5-chloro-2-(5-fluoro-3-pyridyl)-4-(trifluoromethyl)pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	With tris-(dibenzylideneacetone)dipalladium(0); trifuran-2-yl-phosphane; copper(I) 3-metthylsalicylate; In tetrahydrofuran; at 100℃; for 1.5h;Inert atmosphere; Microwave irradiation;	A microwave vial was charged with 5-chloro-2-methylsulfanyl-4- (trifluoromethyl)pyrimidine (750mg, 3.28 mmol), <strong>[872041-86-6](5-fluoro-3-pyridyl)boronic acid</strong> (693mg, 4.92 mmol), tris(2-furyl)phosphane (122mg, 0.525 mmol), copper(l) 3-methylsalicylate (1 .76g, 8.20 mmol), Pd2dba3 (120mg, 0.131 mmol) and anhydrous THF (20 mL) (pre- sparged with N2 for 30 min) and heated at 100C for 1 hour under microwave irradiation. The reaction mixture was evaporated to dryness under reduced pressure and the residue was taken up in Et.20 (200 mL) and washed with aq. NH4OH (2:1 conc.:water, 3 x 200mL) and brine (200mL). The organic phase was dried over MgSC>4 and evaporated to dryness under reduced pressure. The crude product was purified twice by flash chromatography on silica gel, first with an EtOAc/isohexane gradient as eluent followed by a 0-10% MeOH/DCM gradient as eluent to give the desired product (603mg, 66%) as a crystalline pale yellow solid. 1H NMR (400 MHz, CDC ): delta 9.49 (s, 1 H), 9.01 (s, 1 H), 8.63 (d, 1 H), 8.47-8.39 (m, 1 H).
66%	With tris-(dibenzylideneacetone)dipalladium(0); trifuran-2-yl-phosphane; copper(I) 3-metthylsalicylate; In tetrahydrofuran; at 100℃; for 1h;Inert atmosphere; Microwave irradiation;	A microwave vial was charged with 5-chloro-2-methylsulfanyl-4(trifluoromethyl)pyrimidine (750mg, 3.28 mmol), <strong>[872041-86-6](5-fluoro-3-pyridyl)boronic acid</strong> (693mg, 4.92 mmol), tris(2-furyl)phosphane (122mg, 0.525 mmol), copper(l) 3-methylsalicylate (1 .76g, 8.20 mmol), Pd2dba3 (120mg, 0.131 mmol) and anhydrous THF (20 mL) (pre- sparged with N2 for 30 min) and heated at 100C for 1 hour under microwave irradiation. The reaction mixture was evaporated to dryness under reduced pressure and the residue was taken up in Et.20 (200 mL) and washed with aq. NH4OH (2:1 conc.:water, 3 x 200mL) and brine (200mL). The organic phase was dried over MgSC>4 and evaporated to dryness under reduced pressure. The crude product was purified twice by flash chromatography on silica gel, first with an EtOAc/isohexane gradient as eluent followed by a 0-10% MeOH/DCM gradient as eluent to give the desired product (603mg, 66%) as a crystalline pale yellow solid. 1H NMR (400 MHz, CDCb): o 9.49 (s, 1 H), 9.01 (s, 1 H), 8.63 (d, 1 H), 8.47-8.39 (m, 1 H).

Reference： [1]Patent: WO2019/57721,2019,A1 .Location in patent: Page/Page column 30
[2]Patent: WO2019/57722,2019,A1 .Location in patent: Page/Page column 40

71
[ 872041-86-6 ]
tert butyl N-[2-chloro-4-(trifluoromethyl)pyrimidin-5-yl]carbamate [ No CAS ]
tert-butyl N-[2-(5-fluoro-3-pyridyl)-4-(trifluoromethyl)pyrimidin-5-yl]carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%		A mixture of tert-butyl N-[2-chloro-4-(trifluoromethyl)pyrimidin-5-yl]carbamate (0.20g, 0.672 mmol) and <strong>[872041-86-6](5-fluoro-3-pyridyl)boronic acid</strong> (0.133g, 0.941 mmol) in EtOH (0.54 mL), toluene (2 mL) and water (0.92 mL) was sparged with N2 for 30 min at RT. K2CO3 (0.186g, 1 .34 mmol) and Pd(PPh3)4 (0.039g, 0.0336 mmol) were then added and the yellow solution heated to 85C under an N2 atmosphere for 8 hours and cooled to RT overnight. The mixture was diluted with EtOAc (30 mL) and washed with brine (30mL). The aqueous layer was then extracted with further EtOAc (2 x 30 mL) and the combined organic extracts were dried over MgSC>4 and evaporated to dryness under reduced pressure. The crude product was purified by flash chromatography on silica gel using an EtOAc/isohexane gradient as eluent to give the desired product (0.224g, 93%) as a colourless solid. 1H NMR (400 MHz, CDCI3) delta 9.81 (s, 1 H), 9.45 (s, 1 H), 8.58 (d, 1 H), 8.39 (d, 1 H), 6.97 (br. s, 1 H), 1 .58 (m, 9H)
93%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 85℃; for 8h;Inert atmosphere;	A mixture of tert-butyl N-[2-chloro-4-(trifluoromethyl)pyrimidin-5-yl]carbamate (0.20 g, 0.672 mmol) and <strong>[872041-86-6](5-fluoro-3-pyridyl)boronic acid</strong> (0.133 g, 0.941 mmol) in EtOH (0.54 ml_), toluene (2 ml_) and water (0.92 mL) was sparged with N2 for 30 min at RT. K2CO3 (0.186 g, 1 .34 mmol) and Pd(PPh3)4 (0.039g, 0.0336 mmol) were then added and the yellow solution heated to 85 C under an N2 atmosphere for 8 hours and cooled to RT overnight. The mixture was diluted with EtOAc (30 mL) and washed with brine (30ml_). The aqueous layer was then extracted with further EtOAc (2 x 30 mL) and the combined organic extracts were dried over MgS04 and evaporated to dryness under reduced pressure. The crude product was purified by flash chromatography on silica gel using an EtOAc/isohexane gradient as eluent to give the desired product (0.224 g, 93%) as a colourless solid. 1H NMR (400 MHz, CDC ) delta 9.81 (s, 1 H), 9.45 (s, 1 H), 8.58 (d, 1 H), 8.39 (d, 1 H), 6.97 (br s, 1 H), 1 .58 (m, 9H).

Reference： [1]Patent: WO2019/57722,2019,A1 .Location in patent: Page/Page column 34-35
[2]Patent: WO2019/57720,2019,A1 .Location in patent: Page/Page column 32; 33

72
[ 872041-86-6 ]
[ 1616415-55-4 ]
tert butyl N-[2-(5-fluoro-3-pyridyl)-4-methyl-pyrimidin-5-yl]carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	With chlorophenylallyl[1,3-bis-2,6-bis( diphenylmethyl)-4-methylphenyl-imidazol-2-ylidene]palladium(ll); potassium carbonate; In ethanol; at 80℃; for 1h;Inert atmosphere;	mixture of tert-butyl N-(2-chloro-4-methyl-pyrimidin-5-yl)carbamate (212 mg, 0.87 mmol), <strong>[872041-86-6]5-fluoropyridine-3-boronic acid</strong> (160mg, 1.09 mmol), potassium carbonate (265mg, 1 .91 mmol) and [Pd(IPr*)(cin)CI) (50mg, 0.043 mmol) in EtOH (6.40 ml.) was heated at 80C under an N2 atmosphere for 1 hour. The mixture was filtered through celite, washed through with EtOH and evaporated to dryness under reduced pressure to give an orange-brown gum. The crude product was purified by flash chromatography on silica gel using an EtOAc/isohexane gradient as eluent to give the desired product (170mg, 64%) as a yellow solid.1 H NMR (400MHz, CDCb) o = 9.42 (s, 1 H), 9.20 (br s, 1 H), 8.52 (d, 1 H), 8.38 (dd, 1 H),6.55 (br s, 1 H), 2.57 (s, 3H), 1.55 (s, 9H).
64%	With (chloro)phenylallyl[1,3?bis(2,6?bis(diphenylmethyl)?4?methylphenyl)imidazo?2?ylidene]palladium(II); potassium carbonate; In ethanol; at 80℃; for 1h;Inert atmosphere;	A mixture of tert-butyl N-(2-chloro-4-methyl-pyrimidin-5-yl)carbamate (212 mg, 0.87 mmol), <strong>[872041-86-6]5-fluoropyridine-3-boronic acid</strong> (160 mg, 1.09 mmol), potassium carbonate (265 mg, 1 .91 mmol) and [Pd(IPr*)(cin)CI) (50 mg, 0.043 mmol) in EtOH (6.40 mL) was heated at 80 C under an N2 atmosphere for 1 hour. The mixture was filtered through celite, washed through with EtOH and evaporated to dryness under reduced pressure to give an orange-brown gum. The crude product was purified by flash chromatography on silica gel using an EtOAc/isohexane gradient as eluent to give the desired product (170 mg, 64%) as a yellow solid. 1H NMR (400MHz, CDCl3) delta = 9.42 (s, 1 H), 9.20 (br s, 1 H), 8.52 (d, 1 H), 8.38 (dd, 1 H), 6.55 (br s, 1 H), 2.57 (s, 3H), 1 .55 (s, 9H).

Reference： [1]Patent: WO2019/57722,2019,A1 .Location in patent: Page/Page column 31
[2]Patent: WO2019/57720,2019,A1 .Location in patent: Page/Page column 27; 28

73
[ 872041-86-6 ]
(S)-N-(3-amino-1-cyano-3-oxopropyl)-3-((4-bromophenyl)sulfonyl)-2,2-dimethylpropanamide [ No CAS ]
(S)-N-(3-amino-1-cyano-3-oxopropyl)-3-((4-(5-fluoropyridine-3-yl)phenyl)sulphonyl)-2,2-dimethylpropanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In water; N,N-dimethyl-formamide; at 60℃;	General procedure: To a solu of 14 (60 mg, 0.14 mmol) in DMF (2 mL) was added selected aryl boronic acid (0.22 mmol) and 2 M Na2CO3 (0.2 mL). The reaction mixture was degassed with bubbling N2 (g) for 10 mins. Added PdCl2(dppf) (10 mg, 0.013 mmol), heated to 60 C and stirred for 10-30 mins. The reaction was cooled to room temperature, diluted with 5% LiCl (aq. Solu., 16 mL) and extracted with EtOAc (2 x 10 mL). The combined organic extracts were washed with 5% LiCl (aq. Solu., 2 x 15 mL) and brine (20 mL), dried over Na2SO4, passed through a plug of celite and concentrated under vacuum. The residue was purified by column chromatography using 0 to 100% EtOAc in hexanes then 0 to 10% MeOH in EtOAc to afford the desired product:

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 1546 - 1548

74
[ 872041-86-6 ]
N-[5-(7-bromo-8-fluoro-4-oxoquinazolin-3 (4H)-yl)-2-(trifluoromethoxy)phenyl]-1-(morpholin-4-yl)cyclopropane-1-carboxamide [ No CAS ]
N-{5-[8-fluoro-7-(5-fluoropyridin-3-yl)-4-oxoquinazolin-3(4H)-yl]-2-(trifluoromethoxy)phenyl}-1-(morpholin-4-yl)cyclopropane-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,2-dimethoxyethane; water; N,N-dimethyl-formamide; at 80℃; for 2h;Inert atmosphere;	A mixture of N-[5-(7-bromo-8-fluoro-4-oxoquinazolin-3(4H)-yl)-2-(trifluoromethoxy)phenyl]-l - (morpholin-4-yl)cyclopropane-l -carboxamide (70.0 mg, 123 muiotaetaomicron), <strong>[872041-86-6](5-fluoropyridin-3-yl)boronic acid</strong> (27.3 mg, 95 % purity, 184 muiotaetaomicron), [l,l -bis-(diphenylphosphino)-ferrocen]-dichloropalladium (5.00 mg, 6.13 muiotaetaomicron) and potassium carbonate (50.8 mg, 368 muiotaetaomicron) in N,N-dimethylformamide (110 mu), water (440 mu) and 1 ,2-dimethoxyethane (610 mu) was degassed by passing argon through it for 5 min and then the mixture was heated at 80C for 2 h. After cooling to rt, the solvent was evaporated under reduced pressure and the crude material was purified by chromatography over silica gel eluting with a gradient dichloromethane/methanol from 98:2 to 90: 10 (+ 0.2% ammonia). The product fractions were collected and purified once more by preparative RP-HPLC 125x30mm, with acetonitrile/water (0.2% ammonia), to afford 28.5 mg (98 % purity, 38 % yield) of the title compound.LC-MS (Method 6): Rt= 2.09 min; MS (ESIpos): m/z = 588 [M+H]+-NMR (400 MHz, DMSO-d6) delta [ppm] : 1.118 (3.09), 1.131 (8.73), 1.138 (9.49), 1.148 (4.37), 1.233 (0.74), 1.276 (4.21), 1.286 (9.44), 1.293 (7.92), 1.306 (3.33), 1.479 (0.48), 2.327 (1.00), 2.366 (0.93), 2.472 (13.55), 2.670 (1.21), 2.710 (0.97), 3.708 (13.15), 7.430 (4.68), 7.436 (4.54), 7.452 (5.16), 7.458 (5.14), 7.717 (4.14), 7.720 (4.09), 7.739 (3.68), 7.823 (3.42), 7.843 (4.35), 7.860 (3.66), 8.092 (6.61), 8.113 (5.54), 8.142 (3.19), 8.166 (3.23), 8.493 (16.00), 8.598 (9.44), 8.605 (9.30), 8.728 (8.34), 8.735 (8.06), 8.789 (6.85), 10.634 (8.75).

Reference： [1]Patent: WO2019/63704,2019,A1 .Location in patent: Page/Page column 204; 205

75
[ 872041-86-6 ]
N-[5-(7-bromo-8-fluoro-4-oxoquinazolin-3 (4H)-yl)-2-(trifluoromethoxy)phenyl]-2-(morpholin-4-yl)propanamide [ No CAS ]
N-{5-[8-fluoro-7-(5-fluoropyridin-3-yl)-4-oxoquinazolin-3(4H)-yl]-2-(trifluoromethoxy)phenyl}-2-(morpholin-4-yl)propanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,2-dimethoxyethane; water; N,N-dimethyl-formamide; at 80℃; for 2h;Inert atmosphere;	A mixture of N-[5-(7-bromo-8-fluoro-4-oxoquinazolin-3(4H)-yl)-2-(trifluoromethoxy)phenyl]-2- (morpholin-4-yl)propanamide (enantiomer 1) (100 mg, 179 muiotaetaomicron), <strong>[872041-86-6](5-fluoropyridin-3-yl)boronic acid</strong> (37.8 mg, 268 muiotaetaomicron), [l,l-bis-(diphenylphosphino)-ferrocen]-dichloropalladium-dichloromethane- complex (7.30 mg, 8.94 muiotaetaomicron) and potassium carbonate (74.1 mg, 536 muiotaetaomicron) in N,N- dimethylformamide (160 mu), water (680 mu) and 1,2-dimethoxyethane (1.0 ml) was degassed by passing argon through it for 5 min and then the mixture was heated at 80C for 2 h. After cooling to rt, the reaction mixture was directly purified by chromatography over silica gel eluting with a gradient cyclohexane/ethyl acetate from 95:5 to 0: 100 to afford 86.0 mg (99 % purity, 84 % yield) of the title compound.LC-MS (Method 6): Rt= 1.72 min; MS (ESIpos): m/z = 576 [M+H]+-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.149 (0.42), -0.008 (3.60), 0.008 (4.05), 0.146 (0.45), 1.175 (0.81), 1.200 (15.72), 1.217 (16.00), 1.988 (1.23), 2.323 (0.64), 2.327 (0.92), 2.332 (0.64), 2.366 (0.67), 2.518 (5.70), 2.523 (4.83), 2.568 (7.29), 2.580 (4.13), 2.598 (1.65), 2.609 (1.01), 2.665 (0.73), 2.670 (0.98), 2.674 (0.75), 2.710 (0.78), 3.387 (1.28), 3.404 (4.50), 3.422 (4.41), 3.439 (1.23), 3.648 (6.00), 3.659 (10.53), 3.670 (6.00), 7.449 (3.80), 7.456 (3.77), 7.471 (4.27), 7.477 (4.41), 7.689 (3.10), 7.692 (3.21), 7.711 (2.74), 7.714 (2.54), 7.826 (2.74), 7.843 (3.13), 7.847 (3.41), 7.864 (3.10), 8.100 (4.77), 8.121 (4.02), 8.144 (2.35), 8.169 (2.35), 8.449 (6.25), 8.455 (6.25), 8.501 (12.31), 8.730 (5.84), 8.737 (5.72), 8.791 (4.52), 8.795 (4.61), 10.106 (6.42).

Reference： [1]Patent: WO2019/63704,2019,A1 .Location in patent: Page/Page column 240; 241

76
[ 872041-86-6 ]
N-[5-(7-bromo-8-fluoro-4-oxoquinazolin-3 (4H)-yl)-2-(trifluoromethoxy)phenyl]-2-(morpholin-4-yl)propanamide [ No CAS ]
N-{5-[8-fluoro-7-(5-fluoropyridin-3-yl)-4-oxoquinazolin-3(4H)-yl]-2-(trifluoromethoxy)phenyl}-2-(morpholin-4-yl)propanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,2-dimethoxyethane; water; N,N-dimethyl-formamide; at 80℃; for 2h;Inert atmosphere;	A mixture of N-[5-(7-bromo-8-fluoro-4-oxoquinazolin-3(4H)-yl)-2-(trifluoromethoxy)phenyl]-2- (morpholin-4-yl)propanamide (enantiomer 2) (100 mg, 179 muiotaetaomicron), <strong>[872041-86-6](5-fluoropyridin-3-yl)boronic acid</strong> (37.8 mg, 268 muiotaetaomicron), [l,l-bis-(diphenylphosphino)-ferrocen]-dichloropalladium-dichloromethane- complex (7.30 mg, 8.94 muiotaetaomicron) and potassium carbonate (74.1 mg, 536 muiotaetaomicron) in N,N- dimethylformamide (160 mu), water (680 mu) and 1,2-dimethoxyethane (1.0 ml) was degassed by passing argon through it for 5 min and then the mixture was heated at 80C for 2 h. After cooling to rt, the reaction mixture was directly purified by chromatography over silica gel eluting with a gradient cyclohexane/ethyl acetate from 95:5 to 0: 100 to afford 45.0 mg (99 % purity, 44 % yield) of the title compound.LC-MS (Method 6): Rt= 1.72 min; MS (ESIpos): m/z = 576 [M+H]+-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (2.05), 0.008 (2.05), 1.200 (15.74), 1.217 (16.00), 2.328 (0.90), 2.366 (1.54), 2.568 (8.19), 2.580 (4.48), 2.598 (1.79), 2.609 (1.02), 2.670 (1.02), 2.710 (1.54), 3.265 (0.64), 3.387 (1.66), 3.405 (4.61), 3.422 (4.61), 3.439 (1.28), 3.648 (6.53), 3.659 (11.39), 3.670 (6.53), 7.449 (3.46), 7.456 (3.46), 7.471 (3.97), 7.478 (4.10), 7.689 (3.07), 7.693 (3.20), 7.711 (2.69), 7.715 (2.56), 7.827 (2.56), 7.844 (3.07), 7.848 (3.46), 7.865 (3.07), 8.100 (5.12), 8.121 (4.22), 8.144 (2.43), 8.169 (2.43), 8.448 (6.02), 8.455 (6.14), 8.501 (12.16), 8.730 (5.89), 8.737 (5.89), 8.792 (4.74), 8.795 (4.99), 10.108 (6.66).

Reference： [1]Patent: WO2019/63704,2019,A1 .Location in patent: Page/Page column 241; 242

77
[ 872041-86-6 ]
[ 1422513-84-5 ]
3-(5-fluoropyridin-3-yl)-8,8-dimethyl-4H,8H-pyrano[2,3-f]chromen-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61.2%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In tetrahydrofuran; water; at 60℃; for 6h;	General procedure: Na2CO3 (32mg, 0.3mmol), heteroaryl boronic acids (0.12mmol), and tetrakis(triphenylphosphine)palladium (6mg, 5mol %) were added to a solution of 7 (35mg, 0.1mmol) in THF (3mL) and H2O (0.4mL). After 6h stirring at 60C, the mixture was concentrated in vacuo and purified by flash chromatography to give 8v and 8w. 4.1.6.1 3-(5-Fluoropyridin-3-yl)-8,8-dimethyl-4H,8H-pyrano[2,3-f]chromen-4-one (8v) The corresponding heteroaryl boronic acid was <strong>[872041-86-6](5-fluoropyridin-3-yl)boronic acid</strong>. Yellow solid, yield, 61.2%; m.p. 169-170C; 1H NMR (CDCl3, 400MHz) delta: 1.51 (s, 6H), 5.75 (d, J=10.0Hz, 1H), 6.8 (d, J=10.0Hz, 1H), 6.89 (d, J=8.8Hz, 1H), 7.84-7.87 (s, 1H), 8.05 (d, J=8.8Hz, 1H), 8.07 (s, 1H), 8.48 (d, J=2.8Hz, 1H), 8.52 (s, 1H). 13C NMR (CDCl3, 100MHz) delta: 28.3, 78.1, 109.5, 114.8, 115.9, 118.1, 120.8, 124.1, 126.8, 129.7, 130.8, 137.7, 144.4, 152.5, 152.7, 158.0, 160.5, 175.1. HR-TOF-MS (positive mode): m/z calcd. C19H15FNO3 [M+H]+ 324.1036, found 324.1037. HPLC purity: 99.1%.

Reference： [1]Bioorganic Chemistry,2019,vol. 88

78
[ 872041-86-6 ]
8-bromo-3-methylbenzo[e]imidazo[5,1-c][1,2,4]triazine [ No CAS ]
8-(5-fluoropyridin-3-yl)-3-methylbenzo[e]imidazo[5,1-c][1,2,4]triazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 102 - 108℃;Inert atmosphere;	General procedure: brominated compound (1 eq), boronic acid derivative (BA, 8a-8f, 9a-9c, 1.1-1.3 eq), and K2CO3(2-3 eq) were combined in a mixture of 1,4-dioxane and water (4:1). The suspension was degassedwith argon for 5-10 min, and Pd(PPh3)4 (5-10 mol%) was added. The mixture was refluxed (bathtemperature 102-108 C) for 1-2 days until completion of the reaction (as indicated by TLC). Thesolvent was removed, and the residue was partitioned between CHCl3 and water. The aqueous layerwas extracted twice with CHCl3, and the combined organic layers were dried (Na2SO4) and thesolvent evaporated. Unless stated otherwise, the obtained residue was purified by flashchromatography on silica gel using CHCl3/MeOH (10:1) as the eluent. The following productswere isolated:

Reference： [1]Molecules,2019,vol. 24

79
[ 872041-86-6 ]
(R)-6-bromo-2-(3-(1,1,2-trifluoro-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2-yl)phenyl)-4-(trifluoromethyl)isoindolin-1-one [ No CAS ]
(R)-6-(5-fluoropyridin-3-yl)-2-(3-(1,1,2-trifluoro-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2-yl)phenyl)-4-(trifluoromethyl)isoindolin-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; water; at 110℃; for 0.25h;Inert atmosphere; Microwave irradiation;	6-Bromo-2-(3 -( 1 , 1 ,2-trifluoro- 1 -(4-methyl -4H- 1 ,2,4-triazol-3 -yl)propan-2-yl)phenyl)- (3924) 4-(trifluoromethyl)isoindolin-l-one (51 mg, 0.095 mmol, 1.0 eq.), <strong>[872041-86-6](5-fluoropyridin-3-yl)boronic acid</strong> (28 mg, 0.20 mmol, 2.1 eq.) and [1,1'- bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane adduct (5.0 mg, 0.061 mmol, 6.4 mol%) were added to a reaction vessel followed by dioxane (1 mL). 2M-Potassium carbonate solution (150 pL. 0.30 mmol, 3.2 eq.) was added and the reaction was purged with nitrogen. The reaction was heated in a microwave at 110 C for 15 minutes. After cooling, water and chloroform: isopropyl alcohol (2: 1) were added and the reaction partitioned. The product was extracted with chloroform: isopropyl alcohol (2: 1, 2X). The combined organic layers were dried, filtered and concentrated. The crude material was purified by silica gel column chromatography using a gradient of methanol in EtOAc (0 - 20%) to afford the title compound (44 mg, 85%) as a colorless solid. 1H NMR (500 MHz, DMSO-r/6) d 8.99 (t, J= 1.8 Hz, 1H), 8.67 (d, J= 2.7 Hz, 1H), 8.62 (s, 1H), 8.49 - 8.42 (m, 2H), 8.37 (dt, J= 10.3, 2.3 Hz, 1H), 8.04 (d, J= 2.0 Hz, 1H), 7.99 - 7.92 (m, 1H), 7.53 (t, J= 8.0 Hz, 1H), 7.23 (d, J= 7.9 Hz, 1H), 5.27 (d, J= 2.3 Hz, 2H), 3.46 (s, 3H), 2.06 - 1.94 (m, 3H); LCMS: C26H18F7N50 requires: 549, found: m/z = 550 [M+Hf.

Reference： [1]Patent: WO2019/148005,2019,A1 .Location in patent: Paragraph 2289

80
[ 872041-86-6 ]
C₂₅H₂₃BrN₄O [ No CAS ]
C₃₀H₂₆FN₅O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49%	With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; N,N-dimethyl-formamide; at 90℃; for 22h;Inert atmosphere; Sealed tube;	A thick wall glass vessel was charged with compound 143 (345 mg, 0.725 mmol), <strong>[872041-86-6]5-fluoropyridine-3-boronic acid</strong> (153 mg, 1.09 mmol), potassium phosphate tribasic (462 mg, 2.17 mmol), tetrakis(triphenylphosphine)palladium(0) (42 mg, 0.036 mmol), 1,4-dioxane (4 mL) and DMF (2 mL). The vessel was purged with N2 and sealed. Hie reaction mixture was heated at 90 C for 22 h. The mixture was cooled to room temperature, diluted with EtOAc, and filtered through a plug of Celite. The filtrate was washed with sat. aq. KH2PQ4 and brine. The organic extract was dried with NaiSOp filtered, and concentrated. Hie residue was purified by column chromatography (silica gel, eluting with 5% MeOH in EtOAc) to give compound 144 (175 mg, 49% yield) as a white solid m/z = 492 (M+l).

Reference： [1]Patent: WO2019/241796,2019,A1 .Location in patent: Page/Page column 72; 106; 147; 227

81
[ 872041-86-6 ]
C₂₅H₂₃BrN₄O [ No CAS ]
C₃₀H₂₆FN₅O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; N,N-dimethyl-formamide; at 90℃; for 22h;Inert atmosphere; Sealed tube;	A thick wall glass vessel was charged with compound 146 (150 mg, 0 315 mmol), <strong>[872041-86-6]5-fluoropyridine-3-boronic acid</strong> (67 mg, 0.48 mmol), potassium phosphate tribasic (200 mg, 0.945 mmol), tetrakis(triphenylphosphine)palladium(0) (18 mg, 0.0157 mmol), 1,4- dioxane (2 mL), and DMF (1 mL). The vessel was sealed and the reaction mixture was heated at 90 C for 22 h. The mixture was cooled to room temperature, diluted with EtOAc, and filtered through a plug of Celite. The filtrate was washed with sat. aq. KH2PO4 and brine. The organic extract was dried with Na?.S04, filtered, and concentrated. Hie residue was purified by column chromatography (silica gel, eluting with 3% MeOH in EtOAc) to give compound 147b (86 mg, 56% yield) as a glass m/z = 492 (M+l).

Reference： [1]Patent: WO2019/241796,2019,A1 .Location in patent: Page/Page column 72; 107; 147; 229

82
[ 872041-86-6 ]
C₂₆H₂₃BrFN₃O [ No CAS ]
C₃₁H₂₆F₂N₄O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
37%	With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; N,N-dimethyl-formamide; at 90℃; for 23h;Sealed tube; Inert atmosphere;	A thick wall glass vessel was charged with compound 154 (200 mg, 0.406 mmol), potassium phosphate tribasic (258 mg, 1.21 mmol), tetrakis(triphenyl- phosphine)palladium(Q) (23 mg, 0.020 mmol), <strong>[872041-86-6]5-fluoropyridine-3-boronic acid</strong> (85 mg, 0.60 mmol), 1,4-dioxane (2 inL), and DMF (1 inL). The vessel was sealed and the reaction mixture was heated at 90 C for 23 h. The reaction mixture was cooled to room temperature, diluted with EtOAc, and filtered through a plug of Celite. The filtrate was washed with sat aq. KH2PO4 and brine. The organic extract was dried with NaiSOr, filtered, and concentrated. The residue was purified by column chromatography (silica gel, eluting with 60% EtOAc in hexanes) to give compound 155 (77 mg, 37% yield) as a yellow glass m/z = 509 (M+l).

Reference： [1]Patent: WO2019/241796,2019,A1 .Location in patent: Page/Page column 72; 109; 147; 232

83
[ 872041-86-6 ]
1-(4-((2-(1H-indol-3-yl)ethyl)amino)-2-chloro-5,8-dihydropyrido[3,4-d]pyrimidin-7(6H)-yl)ethan-1-one [ No CAS ]
1-(4-((2-(1H-indol-3-yl)ethyl)amino)-2-(5-fluoropyridin-3-yl)-5,8-dihydropyrido[3,4-d]pyrimidin-7(6H)-yl)ethan-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
46%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 100℃;Inert atmosphere;	General procedure: A suitable round bottom flask or reacti-vial was charged with aryl halide (lequiv.), aryl boronic acid (1.5-2.0 equiv.), potassium carbonate (1.5-2.0 equiv.), dioxane/water ([5:1] about 60 vol). Head space was flushed with nitrogen gas, then [l,l'-Bis(diphenylphosphino) ferrocene]dichloropalladium(II) dichloride (0.2-0.3 equiv.) was added. The reaction mixture was heated under nitrogen at 100C for 2-24 h until complete as determined by UPLC analysis. The reaction mixture was evaporated to dryness and applied to a silica column as a slurry in DCM; or preabsorbed onto celite, which was loaded in to a dry load unit and placed in series with a silica cartridge. The desired product was eluted with a gradient of ethyl acetate in hexane, sometimes more polar eluent of methanol (0-10%) in ethyl acetate may be required. Further chromatography on silica eluting with 7M ammonia in methanol (0-10%) in DCM may be required. Trituration with diethyl ether and subsequent filtration afforded the desired product.

Reference： [1]Patent: WO2020/39093,2020,A1 .Location in patent: Page/Page column 15; 16; 17

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	872041-86-6	MDL No. :	MFCD07368243
Formula :	C₅H₅BFNO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	FVEDGBRHTGXPOK-UHFFFAOYSA-N
M.W :	140.91	Pubchem ID :	44717403
Synonyms :

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

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

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

[ CAS No. 872041-86-6 ] {[proInfo.proName]}

Quality Control of [ 872041-86-6 ]

Related Doc. of [ 872041-86-6 ]

Product Details of [ 872041-86-6 ]

Calculated chemistry of [ 872041-86-6 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 872041-86-6 ]

Application In Synthesis of [ 872041-86-6 ]

[ 872041-86-6 ] Synthesis Path-Upstream 1~1

[ 872041-86-6 ] Synthesis Path-Downstream 1~83

Related Functional Groups of
[ 872041-86-6 ]

Fluorinated Building Blocks

Organoboron

Related Parent Nucleus of
[ 872041-86-6 ]

Pyridines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

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

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

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.0

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:

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P378
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