[ CAS No. 338454-14-1 ] {[proInfo.proName]}

Name: 338454-14-1|1H-Indazole-5-boronic acid|98%
Brand: Ambeed
SKU: A1145100
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Quality Control of [ 338454-14-1 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 338454-14-1 ]

SDS Specification

Alternatived Products of [ 338454-14-1 ]

Product Details of [ 338454-14-1 ]

CAS No. :	338454-14-1	MDL No. :	MFCD06739151
Formula :	C₇H₇BN₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	CLVPGJWAMIADSY-UHFFFAOYSA-N
M.W :	161.95	Pubchem ID :	17750504
Synonyms :

Calculated chemistry of [ 338454-14-1 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	9
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	3.0
Molar Refractivity :	45.92
TPSA :	69.14 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.96 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	0.46
Log Po/w (WLOGP) :	-0.76
Log Po/w (MLOGP) :	-0.61
Log Po/w (SILICOS-IT) :	-0.58
Consensus Log Po/w :	-0.3

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.62
Solubility :	3.86 mg/ml ; 0.0238 mol/l
Class :	Very soluble
Log S (Ali) :	-1.48
Solubility :	5.36 mg/ml ; 0.0331 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.79
Solubility :	2.62 mg/ml ; 0.0162 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.79

Safety of [ 338454-14-1 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 338454-14-1 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Downstream synthetic route of [ 338454-14-1 ]

[ 338454-14-1 ] Synthesis Path-Downstream 1~66

1
[ 338454-14-1 ]
[ 767316-21-2 ]
N-[4-(1H-benzoimidazol-2-yl)-phenyl]-3-(1H-indazol-5-yl)-4-methoxy-benzamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 404 - 408

2
[ 53857-57-1 ]
[ 338454-14-1 ]

Yield	Reaction Conditions	Operation in experiment
19%		5-Bromoindazole (638 mg; 3.24 mmol) is initially introduced into diethyl ether (10 ml), and a 1.6 M n-butyllithium solution in n-hexane (4.05 ml; 6.48 mmol) is added at -20 C. (cooling bath) in the course of 15 minutes. The cooling bath is removed, the reaction mixture is subsequently stirred for one hour at room temperature and then diluted with diethyl ether (10 ml), and stirring is continued for 90 minutes at room temperature and 15 minutes at 30 C. The reaction mixture is then poured at -70 C. on to a solution comprising trimethyl borate (0.36 ml; 3.24 mmol) in diethyl ether (5 ml). The reaction mixture is allowed to warm to room temperature and is subsequently stirred for 3 hours at room temperature. Diethyl ether (20 ml) is then added to the reaction mixture and stirring is continued for 12 hours at room temperature. Thereafter, the reaction mixture is poured on to aqueous 1 N hydrochloric acid and extracted with diethyl ether and the extract is dried over magnesium sulphate, filtered with suction and concentrated. The residue is chromatographed over silica gel (100 g) with methylene chloride/methanol (97.5/2.5 to 90/10). [00193] Yield: 100 mg (19%) 5-(1H-indazole)-boron acid as a beige powder. MS (ISN): 161.3(M-H)-

Reference： [1]Patent: US6821980,2004,B1 .Location in patent: Page column 24

3
[ 338454-14-1 ]
[ 864773-75-1 ]
1,1-dimethylethyl [(1S)-2-(1-benzothien-3-yl)-1-([6-chloro-5-(1H-indazol-5-yl)-3-pyridinyl]oxy}methyl)ethyl]carbamate [ No CAS ]

Reference： [1]Patent: WO2005/85227,2005,A1 .Location in patent: Page/Page column 47

4
[ 338454-14-1 ]
[ 274680-32-9 ]
[ 1236071-85-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 3636 - 3639

5
[ 338454-14-1 ]
[ 1236071-58-1 ]
[ 1236071-71-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 3636 - 3639

6
[ 338454-14-1 ]
[ 1236071-59-2 ]
[ 1236071-79-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 3636 - 3639

7
[ 338454-14-1 ]
[ 286943-07-5 ]
[ 1236071-62-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 3636 - 3639

8
[ 338454-14-1 ]
[ 1326714-08-2 ]
[ 1326714-77-5 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; XPhos;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,2-dimethoxyethane; water; at 100℃; for 0.666667h;Inert atmosphere; Microwave irradiation;	Step A: ferf-butyl 4-{4-r7-amino-2-(1 /-/-indazol-5-yl)furo[2.3-clDyridine-4-yll-1H-pyrazol-1 - yl}piperidine-1-carboxylateA vial was charged with ferf-butyl 4-[4-(7-amino-2-chlorofuro[2,3-c]pyridine-4-yl)-1 - - pyrazol-1-yl]piperidine-1-carboxylate (50 mg, 0.12 mmol), 5-indazole boronic acid (45 mg, 0.18 mmol), Cs2C03 (55 mg, 0.174 mmol), Pd(dppf)CI2 (20 mg) and 2-dicyclohexylphosphino- 2',4',6'-triisopropylbiphenyl (40 mg) in DME (3 mL) and H20 (0.3 mL) under N2. The mixture was heated to 100 C for 40 min in a microwave reactor. Water (20 mL) was added, and the mixture was extracted with EtOAc (3 x 20 mL). The combined organic layers were dried over Na2S04, filtered and concentrated in vacuo. The residue was purified by preparative TLC (EtOAc) to afford the desired /V-Boc protected intermediate, which was used immediately.

Reference： [1]Patent: WO2011/100502,2011,A1 .Location in patent: Page/Page column 68

9
[ 338454-14-1 ]
[ 225382-62-7 ]
C₁₃H₇ClN₄S [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 5952 - 5956

10
[ 338454-14-1 ]
[ 1021918-69-3 ]
[ 1021916-24-4 ]

Yield	Reaction Conditions	Operation in experiment
10%	With potassium dihydrogenphosphate; 1,1'-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex; In dichloromethane; water; N,N-dimethyl-formamide; at 120℃; for 0.25h;Inert atmosphere; Microwave irradiation;	General procedure: Substrate (1 equiv) and boronic acid (1.2 equiv) were dissolved in DMF (10 mL). Nitrogen was bubbled through the solution for 2 min. An appropriate base in water (5 mL) and Pd catalyst (0.1 equiv) were added. The solution was then heated in a Biotage Emrys Optimizer microwave reactor at 120 C for 15 min. Upon consumption of the starting material, the solution was condensed under reduced pressure. The resulting material was diluted with ethyl acetate and filtered through Celite. The filtrate was condensed under reduced pressure to afford the crude product.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 6793 - 6799

11
[ 338454-14-1 ]
[ 1254583-31-7 ]
[ 1254583-86-2 ]

Yield	Reaction Conditions	Operation in experiment
45%	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 80℃; for 36h;Sealed tube; Inert atmosphere;	Step le: Synthesis of tetraisopropyl ( 2-( 5-( 1 1 i-indazol-5-yl )pyridin-3-yi )- 1 -tluoroethane- 1.1 - diyl )bis(phosphonate ) Tetraisopropyl (2-(5-bromopyridin-3-yl)- 1 -fluoroethane- 1 , 1 -diyl)bis(phosphonate) (85 nig; 0.16 mmol), Pd(PPh3)4 (36.9 mg; 0.032 mmol) and (lH-indazol-5-yl)boronic acid (39 mg; 0.24 mmol) are added to the vial and the vial is capped with a septum. DME (4 inL i is added and the vial is flushed with argon, an aqueous solution of potassium carbonate (2.5 eq.) is added and the mixture is flushed again with argon. The reaction mixture is stirred at 80 C for 36 h under an atmosphere of argon. The mixture was cooled to RT. diluted with EtOAc and filtered through Celite, the Celite is washed three times with EtOAc/MeOH (1 : 1). The filtrate is deposited on silica gel and purified by column chromatography (on pre washed silica with 1% NHt;; in hexanes) using a solvent gradient from hexanes to EtOAc and then to 50% MeOH in EtOAc. The pure product is isolated as a brown oil (41 mg, 45% yield).M l NMR (300 MHz, CDCI3) delta 8.77 (d, J = 2.2 Hz, 1 1 1 ). 8.50 (s, 1 H). 8.15 (s, 1H), 7.95 (s, 1 IT). 7.92 (s, lH), 7.61 (s, 2H), 4.84 (m, 4H), 3.69 - 3.44 (m, 2H), 1.43 - 1.13 (m, 24H).31P NMR (81 MHz, CDC h) delta 9.54 (d, J= 74.8 Hz).

Reference： [1]Patent: WO2011/147038,2011,A1 .Location in patent: Page/Page column 38-39

12
[ 338454-14-1 ]
[ 1365534-11-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 1940 - 1943

13
[ 338454-14-1 ]
[ 1365534-36-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 1940 - 1943

14
[ 338454-14-1 ]
C₁₈H₁₄N₄O [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 1940 - 1943

15
[ 338454-14-1 ]
C₁₇H₁₂N₄O [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 1940 - 1943

16
[ 338454-14-1 ]
[ 1365534-42-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 1940 - 1943

17
[ 338454-14-1 ]
[ 89466-42-2 ]
[ 1365534-31-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 1940 - 1943

18
[ 338454-14-1 ]
[ 1268867-67-9 ]
[ 1268864-76-1 ]

Reference： [1]Patent: WO2012/119046,2012,A2

19
[ 338454-14-1 ]
[ 1268867-67-9 ]
[ 1394971-33-5 ]

Yield	Reaction Conditions	Operation in experiment
45%	With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 90℃; for 0.333333h;Inert atmosphere;	Step 1. Methyl 2-(lH-indazol-5-yl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylateTo a solution of methyl 2-chloro-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylate (Scheme I, 200.0 mg, 0.68 mmol) in 1,4-dioxane (1 mL), was added lH-indazol-5-ylboronic acid (386.0 mg, 2.38 mmol), K3P04 (434.0 mg, 2.05 mmol), Pd(PPh3)4 (39.0 mg, 0.03 mmol) under nitrogen atmosphere and water (3 drops). After stirring for 20 min at 90C, the reaction mixture was dissolved in water (30 mL), extracted with dichloromethane (3 x 20 mL), dried over anhydrous magnesium sulfate and concentrated under reduced pressure to afford a residue, which was purified by a silica gel column with 2% - 10% ethyl acetate in petroleum ether to afford methyl 2-(lH-indazol-5-yl)-3-(isopropyl(methyl)amino)quinoxaline-6- carboxylate as a light yellow solid (110.0 mg, 45%).LC/MS (ES, m/z): [M+H]+ 376.0'H-NMR (300 MHz, DMSO) delta 13.27 (s, 1H), 8.29 (d, / = 9.6 Hz, 2H), 8.22 (s, 1H), 7.86 - 7.99 (m, 3H), 7.67 (d, / = 8.7 Hz, 1H), 4.19 - 4.23 (t, / = 6.6 Hz, 1H), 3.93 (s, 3H), 2.70 (s, 3H), 1.01 (d, 7 = 6.6 Hz, 6H)
45%	With potassium phosphate; water;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 90℃; for 0.333333h;Inert atmosphere;	EXAMPLE 12 Methyl 2-(1H-indazol-5-yl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylate To a solution of methyl 2-chloro-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylate (Scheme I, 200.0 mg, 0.68 mmol) in 1,4-dioxane (1 mL), was added <strong>[338454-14-1]1H-indazol-5-ylboronic acid</strong> (386.0 mg, 2.38 mmol), K3PO4 (434.0 mg, 2.05 mmol), Pd(PPh3)4 (39.0 mg, 0.03 mmol) under nitrogen atmosphere and water (3 drops). After stirring for 20 min at 90 C., the reaction mixture was dissolved in water (30 mL), extracted with dichloromethane (3×20 mL), dried over anhydrous magnesium sulfate and concentrated under reduced pressure to afford a residue, which was purified by a silica gel column with 2%-10% ethyl acetate in petroleum ether to afford methyl 2-(1H-indazol-5-yl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylate as a light yellow solid (110.0 mg, 45%).LC/MS (ES, m/z): [M+H]+ 376.01H-NMR (300 MHz, DMSO) delta 13.27 (s, 1H), 8.29 (d, J=9.6 Hz, 2H), 8.22 (s, 1H), 7.86-7.99 (m, 3H), 7.67 (d, J=8.7 Hz, 1H), 4.19-4.23 (t, J=6.6 Hz, 1H), 3.93 (s, 3H), 2.70 (s, 3H), 1.01 (d, J=6.6 Hz, 6H)

Reference： [1]Patent: WO2012/119046,2012,A2 .Location in patent: Page/Page column 49
[2]Patent: US2012/225863,2012,A1 .Location in patent: Page/Page column 21-22

20
[ 338454-14-1 ]
[ 1394972-91-8 ]
[ 1396751-34-0 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 90℃; for 1h;	Step 2. 3-(Cyclopropyl(methyl)amino)-2-(lH-indazol-5-yl)quinoxaline-6-carboxylateTo a solution of methyl 3-(cyclopropyl(methyl)amino)-2-(trifluoromethylsulfonyloxy)quinoxaline-6-carboxylate (300 mg, crude) in dioxane (10 mL), lH-indazol-5-ylboronic acid (430 mg, 1.76 mmol), K3PO4 (370 mg, 1.76 mmol), and Pd(PPh3)4 (51mg, 0.04 mmol). The resulting solution was stirred for lh at 90C. The resulting mixture was concentrated under vacuum to give a residue, which was purified by a silica gel column with 5% ~ 50% ethyl acetate in petroleum ether to afford methyl 3- (cyclopropyl(methyl)amino)-2-(lH-indazol-5-yl)quinoxaline-6-carboxylate as a yellow solid (40 mg).LC/MS (ES, m/z): [M+H]+ 374.0'H-NMR (300 MHz, CDC13) delta 8.96 (s, 1H), 8.28 (s, 2H), 8.10 - 8.18 (m, 2H), 7.88 (d, / = 7.8 Hz, 1H), 7.68 (d, / = 8.7 Hz, 2H), 4.02 (s, 3H), 2.70 - 2.80 (m, 1H), 0.83- 0.92 (m, 4H)

Reference： [1]Patent: WO2012/119046,2012,A2 .Location in patent: Page/Page column 87-88

21
[ 338454-14-1 ]
[ 1268864-76-1 ]

Reference： [1]Patent: US2012/225863,2012,A1

22
[ 338454-14-1 ]
[ 1394971-58-4 ]

Reference： [1]Patent: US2012/225863,2012,A1

23
[ 338454-14-1 ]
[ 1394973-08-0 ]

Reference： [1]Patent: US2012/225863,2012,A1

24
[ 338454-14-1 ]
[ 1394973-07-9 ]

Reference： [1]Patent: US2012/225863,2012,A1

25
[ 338454-14-1 ]
[ 1422970-01-1 ]
tert-butyl ((2S,3R)-1-(3-(1H-indazol-5-yl)-benzenesulfonamido)-3-(tert-butoxy)-1-oxobutan-2-yl)carbamate [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 1748 - 1760

26
[ 338454-14-1 ]
[ 1440252-09-4 ]
[ 1440251-23-9 ]

Yield	Reaction Conditions	Operation in experiment
51%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 110℃; for 0.5h;Microwave irradiation; Combinatorial reaction / High throughput screening (HTS);	General procedure: 2-Chloro-N-(3,4- dichlorobenzyl)pyridine-4-amine, 4d (30.0 mg, 0.10 mmol, 1.0 equiv) was dissolved in dioxane (2 mL) in a 5-mL microwave vial, and <strong>[338454-14-1]1H-<strong>[338454-14-1]indazole-5-boronic acid</strong></strong> (33.7 mg, 0.20 mmol, 2.0 equiv), aqueous Na2CO3 (0.69 M, 0.43 mL, 0.30 mmol, 3.0 equiv), and Pd(PPh3)4 (11.6 mg, 0.010 mmol, 0.10 equiv) were added. The vial was capped and heated under microwave irradiation for 30 minutes at 110 C. Using stackable 24-position Bohdan MiniBlock XTs, the crude reaction mixture was poured into a phase separator containing CH2Cl2 (2 mL)/saturated aqueous NaHCO3 (2 mL). The bottom organic layer was passed into a new reaction tube, and CH2Cl2 (2 mL) was added to the closed phase separator. The biphasic solution was mixed by hand with a pipette, and the organic layer was again passed into the tube containing the organic layer from the first separation. The combined organic layers were placed on a sample concentrator until the solvent was mostly removed. A solution of TFA/MeOH (1:19, 3 mL) was added to the crude reaction mixture and the sample was shaken at 450 rpm for one hour. The solution was then passed onto a column of Dowex 50WX4-400 ion exchange resin (1.0 g, pre-washed with TFA/MeOH (1:99, 5 mL)). The tube was washed with MeOH (2 mL) and the washings were passed onto the Dowex column. The column was washed with MeOH (3 mL), and the product was then eluted with Et3N/MeOH (1:9, 10 mL). The solution containing the product was placed on a sample concentrator to remove solvents, and then subjected to preparative reverse-phase HPLC purification.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 3654 - 3661

27
[ 338454-14-1 ]
[ 1247084-80-5 ]
[ 1440251-45-5 ]

Yield	Reaction Conditions	Operation in experiment
25%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 110℃; for 0.5h;Microwave irradiation; Combinatorial reaction / High throughput screening (HTS);	General procedure: 2-Chloro-N-(3,4- dichlorobenzyl)pyridine-4-amine, 4d (30.0 mg, 0.10 mmol, 1.0 equiv) was dissolved in dioxane (2 mL) in a 5-mL microwave vial, and <strong>[338454-14-1]1H-<strong>[338454-14-1]indazole-5-boronic acid</strong></strong> (33.7 mg, 0.20 mmol, 2.0 equiv), aqueous Na2CO3 (0.69 M, 0.43 mL, 0.30 mmol, 3.0 equiv), and Pd(PPh3)4 (11.6 mg, 0.010 mmol, 0.10 equiv) were added. The vial was capped and heated under microwave irradiation for 30 minutes at 110 C. Using stackable 24-position Bohdan MiniBlock XTs, the crude reaction mixture was poured into a phase separator containing CH2Cl2 (2 mL)/saturated aqueous NaHCO3 (2 mL). The bottom organic layer was passed into a new reaction tube, and CH2Cl2 (2 mL) was added to the closed phase separator. The biphasic solution was mixed by hand with a pipette, and the organic layer was again passed into the tube containing the organic layer from the first separation. The combined organic layers were placed on a sample concentrator until the solvent was mostly removed. A solution of TFA/MeOH (1:19, 3 mL) was added to the crude reaction mixture and the sample was shaken at 450 rpm for one hour. The solution was then passed onto a column of Dowex 50WX4-400 ion exchange resin (1.0 g, pre-washed with TFA/MeOH (1:99, 5 mL)). The tube was washed with MeOH (2 mL) and the washings were passed onto the Dowex column. The column was washed with MeOH (3 mL), and the product was then eluted with Et3N/MeOH (1:9, 10 mL). The solution containing the product was placed on a sample concentrator to remove solvents, and then subjected to preparative reverse-phase HPLC purification.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 3654 - 3661

28
[ 338454-14-1 ]
[ 1241669-84-0 ]
[ 1440251-29-5 ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 110℃; for 0.5h;Microwave irradiation; Combinatorial reaction / High throughput screening (HTS);	General procedure: 2-Chloro-N-(3,4- dichlorobenzyl)pyridine-4-amine, 4d (30.0 mg, 0.10 mmol, 1.0 equiv) was dissolved in dioxane (2 mL) in a 5-mL microwave vial, and <strong>[338454-14-1]1H-<strong>[338454-14-1]indazole-5-boronic acid</strong></strong> (33.7 mg, 0.20 mmol, 2.0 equiv), aqueous Na2CO3 (0.69 M, 0.43 mL, 0.30 mmol, 3.0 equiv), and Pd(PPh3)4 (11.6 mg, 0.010 mmol, 0.10 equiv) were added. The vial was capped and heated under microwave irradiation for 30 minutes at 110 C. Using stackable 24-position Bohdan MiniBlock XTs, the crude reaction mixture was poured into a phase separator containing CH2Cl2 (2 mL)/saturated aqueous NaHCO3 (2 mL). The bottom organic layer was passed into a new reaction tube, and CH2Cl2 (2 mL) was added to the closed phase separator. The biphasic solution was mixed by hand with a pipette, and the organic layer was again passed into the tube containing the organic layer from the first separation. The combined organic layers were placed on a sample concentrator until the solvent was mostly removed. A solution of TFA/MeOH (1:19, 3 mL) was added to the crude reaction mixture and the sample was shaken at 450 rpm for one hour. The solution was then passed onto a column of Dowex 50WX4-400 ion exchange resin (1.0 g, pre-washed with TFA/MeOH (1:99, 5 mL)). The tube was washed with MeOH (2 mL) and the washings were passed onto the Dowex column. The column was washed with MeOH (3 mL), and the product was then eluted with Et3N/MeOH (1:9, 10 mL). The solution containing the product was placed on a sample concentrator to remove solvents, and then subjected to preparative reverse-phase HPLC purification.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 3654 - 3661

29
[ 338454-14-1 ]
[ 1440252-01-6 ]
[ 1440251-47-7 ]

Yield	Reaction Conditions	Operation in experiment
22%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 110℃; for 0.5h;Microwave irradiation; Combinatorial reaction / High throughput screening (HTS);	2-Chloro-N-(3,4- dichlorobenzyl)pyridine-4-amine, 4d (30.0 mg, 0.10 mmol, 1.0 equiv) was dissolved in dioxane (2 mL) in a 5-mL microwave vial, and <strong>[338454-14-1]1H-<strong>[338454-14-1]indazole-5-boronic acid</strong></strong> (33.7 mg, 0.20 mmol, 2.0 equiv), aqueous Na2CO3 (0.69 M, 0.43 mL, 0.30 mmol, 3.0 equiv), and Pd(PPh3)4 (11.6 mg, 0.010 mmol, 0.10 equiv) were added. The vial was capped and heated under microwave irradiation for 30 minutes at 110 C. Using stackable 24-position Bohdan MiniBlock XTs, the crude reaction mixture was poured into a phase separator containing CH2Cl2 (2 mL)/saturated aqueous NaHCO3 (2 mL). The bottom organic layer was passed into a new reaction tube, and CH2Cl2 (2 mL) was added to the closed phase separator. The biphasic solution was mixed by hand with a pipette, and the organic layer was again passed into the tube containing the organic layer from the first separation. The combined organic layers were placed on a sample concentrator until the solvent was mostly removed. A solution of TFA/MeOH (1:19, 3 mL) was added to the crude reaction mixture and the sample was shaken at 450 rpm for one hour. The solution was then passed onto a column of Dowex 50WX4-400 ion exchange resin (1.0 g, pre-washed with TFA/MeOH (1:99, 5 mL)). The tube was washed with MeOH (2 mL) and the washings were passed onto the Dowex column. The column was washed with MeOH (3 mL), and the product was then eluted with Et3N/MeOH (1:9, 10 mL). The solution containing the product was placed on a sample concentrator to remove solvents, and then subjected to preparative reverse-phase HPLC purification.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 3654 - 3661

30
[ 338454-14-1 ]
[ 1464155-32-5 ]
[ 1464151-23-2 ]

Yield	Reaction Conditions	Operation in experiment
19%	With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; water; at 110℃; for 0.5h;	(4-(3 -bromoimidazo[ 1 ,2-b]pyridazin-6-yl)phenyl)(4-methylpiperazin- 1 -yl)methanone ( 100 mg, 0.250 mmol), lH-indazol-5-ylboronic acid (49 mg, 0.300 mmol), Pd(PPh3)4 (29 mg, 0.025 mmol) and Cs2C03 (163 mg, 0.500 mmol) was dissolved in dioxane (2.0 mL) and water (0.5 mL). The reaction mixture was heated in a microwave reactor for 30 min at 110 C, then it was diluted with water (25 mL) and extracted with EtOAc (3x25 mL). The combined organic layer was filtered through celite, dried over Na2S04 and was concentrated under reduced pressure. The crude residue was purified by preparative HPLC (CI 8, eluent ACN, water, formic acid 0.1%) to afford (4-(3-(lH-indazol-5-yl)imidazo[l,2-b]pyridazin-6- yl)phenyl)(4-methylpiperazin-l-yl)methanone (21 mg, 19%, AUC HPLC 99%) as a yellow solid. 1H NMR (400 MHz, CDC13) delta 8.62 (s, IH), delta 8.20 (s, IH), 8.13-8.05 (m, 5H), 7.66 (d, J= 8.8 Hz, IH), 7.59-7.53 (m, 3H), 3.84 (bs, 2H), 3.50 (bs, 2H), 2.51-2.34 (m, 7H); MS (ESI) m/z 438 [C25H23N 0 + H]+.
19%	With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; water; at 110℃; for 0.5h;Microwave irradiation;	4-(3-bromoimidazo[1,2-b]pyridazin-6-yl)phenyl)(4-methylpiperazin-1-yl)methanone (100 mg, 0.250 mmol), <strong>[338454-14-1]1H-indazol-5-ylboronic acid</strong> (49 mg, 0.300 mmol), Pd(PPh3)4 (29 mg, 0.025 mmol) and Cs2CO3 (163 mg, 0.500 mmol) was dissolved in dioxane (2.0 mL) and water (0.5 mL). The reaction mixture was heated in a microwave reactor for 30 min at 110 C., then it was diluted with water (25 mL) and extracted with EtOAc (3*25 mL). The combined organic layer was filtered through celite, dried over Na2SO4 and was concentrated under reduced pressure. The crude residue was purified by preparative HPLC (C18, eluent ACN, water, formic acid 0.1%) to afford (4-(3-(1H-indazol-5-yl)imidazo[1,2-b]pyridazin-6-yl)phenyl)(4-methylpiperazin-1-yl)methanone (21 mg, 19%, AUC HPLC 99%) as a yellow solid. 1H NMR (400 MHz, CDCl3) delta 8.62 (s, 1H), delta 8.20 (s, 1H), 8.13-8.05 (m, 5H), 7.66 (d, J=8.8 Hz, 1H), 7.59-7.53 (m, 3H), 3.84 (bs, 2H), 3.50 (bs, 2H), 2.51-2.34 (m, 7H); MS (ESI) m/z 438 [C25H23N7O+H]+.

Reference： [1]Patent: WO2013/147711,2013,A1 .Location in patent: Page/Page column 164
[2]Patent: US2014/371199,2014,A1 .Location in patent: Paragraph 0602

31
[ 338454-14-1 ]
7-bromo-3-(3-chlorophenyl)pyrido[2,3-b]pyrazine [ No CAS ]
3-(3-chlorophenyl)-7-(1H-indazol-5-yl)pyrido[2,3-b]pyrazine [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 6152 - 6155

32
[ 338454-14-1 ]
[ 58914-17-3 ]
7-(1H-indazol-5-yl)-3-phenylpyrido[2,3-b]pyrazine [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 6152 - 6155

33
[ 338454-14-1 ]
7-bromo-3-(4-fluorophenyl)pyrido[2,3-b]pyrazine [ No CAS ]
3-(4-fluorophenyl)-7-(1H-indazol-5-yl)pyrido[2,3-b]pyrazine [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 6152 - 6155

34
[ 338454-14-1 ]
[ 862723-42-0 ]
(S)-methyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-2-(2-chloropyridin-4-yl)-5-methylbenzo[d]thiazol-6-yl)acetate [ No CAS ]
(S)-methyl 2-(2-(2-(1H-indazol-5-yl)pyridin-4-yl)-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Preparation of (S)-methyl 2-(2-(2-(1H-indazol-5-yl)pyridin-4-yl)-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate: A microwave tube was charged with (S)-methyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-2-(2-chloropyridin-4-yl)-5-methylbenzo[d]thiazol-6-yl)acetate (25.0 mg, 48.5 mumol), 5-(4?,4?,5?,5?-tetramethyl-1?,3?,2?-dioxaborolan-2?-yl)-1H-indazole (14.2 mg, 58.2 mumol), Pd(PPh3)4 (5.6 mg, 4.86 mumol), K2CO3 (27 mg, 0.19 mmol), H2O (400 muL), and dioxane (1.6 mL). The reaction was sealed and heated to 110 C. The reaction failed to reach completion during the next 2 h (boronate ester was fully consumed (LCMS analysis), yet (S)-methyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-2-(2-chloropyridin-4-yl)-5-methylbenzo[d]thiazol-6-yl)acetate remained.). The reaction was cooled to 23 C. and charged with more 5-(4?,4?,5?,5?-tetramethyl-1?,3?,2?-dioxaborolan-2?-yl)-1H-indazole (10 mg, 41 mumol). Heating to 110 C. was continued. Reaction progressed further, but was still incomplete after 1 h. Again, the reaction was cooled to 23 C. and this time charged with 1H-indazole-5-boronic acid (20 mg, 120 mumol) and K2CO3 (15 mg, 0.11 mmol); heating to 110 C. was resumed. Reaction reached completion in 1 h. The crude product (S)-methyl 2-(2-(2-(1H-indazol-5-yl)pyridin-4-yl)-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate was detected in solution. The solution was used crude in the next reaction. LCMS-ESI+: calc'd for C33H29ClN4O3S: 597.2 and 599.2 (M+H+). Found: 597.3 and 599.3 (M+H+).

Reference： [1]Patent: US2013/281433,2013,A1 .Location in patent: Paragraph 0880

35
[ 338454-14-1 ]
ethyl (S)-2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-(tert-butoxy)acetate [ No CAS ]
(S)-ethyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-2-(1H-indazol-5-yl)-5-methylbenzo[d]thiazol-6-yl)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 95℃; for 6.5h;Microwave irradiation; Sealed tube; Inert atmosphere;	(S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate (300.0 mg, 0.604 mmol), <strong>[338454-14-1]1H-<strong>[338454-14-1]indazole-5-boronic acid</strong></strong> (117.3 mg, 0.725 mmol), potassium carbonate (250.3 mg, 1.811 mmol), and tetrakis(triphenylphosphine)palladium(0) (104.7 mg, 0.091 mmol) were taken in a microwave vial, and the vial was vacuum pumped and flushed with argon three times. To this mixture was added degassed 1,4-dioxane (6 mL) and degassed water (1.5 mL). The reaction mixture was heated at 95 C. for 6.5 h then cooled to room temperature. The reaction mixture was filtered through Celite (ethyl acetate eluent) and concentrated. Purification by flash column chromatography on silica gel (hexanes/ethyl acetate eluent) provided the product. LCMS-ESI+: calc'd for C29H29ClN3O3S: 534.2 (M+H+). Found: 533.8 (M+H+). Preparation of (S)-2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(2-(oxetan-3-yl)-2H-indazol-5-yl)benzo[d]thiazol-6-yl)acetic acid and (S)-2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(1-(oxetan-3-yl)-1H-indazol-5-yl)benzo[d]thiazol-6-yl)acetic acid:

Reference： [1]Patent: US2013/281433,2013,A1 .Location in patent: Paragraph 1474

36
[ 338454-14-1 ]
[ 1532-97-4 ]
[ 1610790-51-6 ]

Reference： [1]ACS Medicinal Chemistry Letters,2014,vol. 5,p. 760 - 765

37
[ 338454-14-1 ]
[ 1533423-93-6 ]
N₃-[3,5-dichloro-4-(1H-indazol-5-yl)phenyl]-1H-[1,2,4]triazole-3,5-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In water; butan-1-ol; at 120℃; for 0.5h;Inert atmosphere; Microwave irradiation;	To a 1 5 m L microwave vial was added 3-(4-bromo-3,5-dichlorophenyl )- 1 H- 1 ,2,4-triazole-3,5- diamine Intermediate 2 (201 mg, 622 umol, Eq: 1 .00), I H - i n d a zo I - 5 - y I bo ro n i c acid (121 mg, 747 Limol, Eq: 1 .2 ) and Cs2C03(507 mg, 1 .56 mmol. Eq : 2.5 ) in Dioxanc (3 ml ) and Water (600 mu). PdCi2(DPPF) (40.7 mg, 49.8 mupiiotaomicron, Eq: 0.08) was added, the mixture was purged with argon, the vial was capped and heated in the microwave at 120C for 30 min. Diluted with dichloromcthane, added Na2S04and filtered through celite. The filtrate was concentrated and the crude material was purified by preparative HPLC (0. 1 %TFA in water/0.1 % TFA in AcCN) 95% to 10% TFA water over 25mins. Dried under vacuum overnight to afford 56 mg (25%) of the desired product as an off white solid.

Reference： [1]Patent: WO2014/135495,2014,A1 .Location in patent: Page/Page column 417; 418

38
[ 338454-14-1 ]
[ 24424-99-5 ]
[ 1167418-12-3 ]

Yield	Reaction Conditions	Operation in experiment
68%	With dmap; triethylamine; In acetonitrile; at 25℃;	A solution of <strong>[338454-14-1](1H-indazol-5-yl)boronic acid</strong> (300 mg, 1.85 mmol, 1.00 equiv), triethylamine (280 mg), Boc2O (804 mg, 3.68 mmol, 1.99 equiv) and 4-dimethylaminopyridine (23 mg, 0.19 mmol, 0.10 equiv) in acetonitrile (15 mL) was stirred at 25 C. overnight. Water (20 mL) was then added and the resulting mixture was extracted with 3×60 mL of ethyl acetate. The combined organic extracts was washed with 2×3 mL of water and 3×3 mL of brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified on a silica gel column eluted with 0-5% of methanol in dichloromethane to give 320 mg (68%) of 1-(tert-butoxycarbonyl)-<strong>[338454-14-1]1H-indazol-5-ylboronic acid</strong> as a white solid. LCMS (method A, ESI): RT=1.34 min, m/z=263.0 [M+H]+.

Reference： [1]Patent: US2014/288105,2014,A1 .Location in patent: Paragraph 0228-0229

39
[ 338454-14-1 ]
tert-butyl 5-(4-(((2-(tert-butoxycarbonylamino)ethyl)(methyl)amino)methyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-yl)-1H-indazole-1-carboxylate [ No CAS ]

Reference： [1]Patent: US2014/288105,2014,A1

40
[ 338454-14-1 ]
N<SUP>1</SUP>-((3-(1H-indazol-5-yl)-1H-pyrazol-4-yl)methyl)-N<SUP>1</SUP>-methylethane-1,2-diamine [ No CAS ]

Reference： [1]Patent: US2014/288105,2014,A1

41
[ 338454-14-1 ]
N-(6-bromopyridin-2-yl)-2-phenylacetamide [ No CAS ]
C₂₀H₁₆N₄O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; at 130℃; for 1h;Microwave irradiation;	General procedure: Scheme 18, step 4 COMPOUND 101. A mixture of N-(6-chloropyridin-3-yl)-2-phenylacetamide (47.5 mg, 0.193 mmol), (5 -(4,4,5,5 -tetramethyl- 1,3 ,2-dioxaborolan-2-yl)indolin- 1 -yl)(o-tolyl)methanone (50 mg, 0.138 mmol), Pd(Ph3P)4 (15.91 mg,0.014 mmol) and Na2CO3 (0.206 ml, 0.413 mmol) in DME (1.3 ml) was heated in a microwave with stirring at 130 C for 1 hr. The reaction mixture was concentrated under a stream of air. The residue was taken up in EtOAc, dried with MgSO4, and filtered through an Agilent PL-Thiol MP SPE cartridge to remove palladium. Theorganic layer was concentrated under a stream of air. The residue was taken up inDMSO and subsequently purified by reverse phase chromatography to afford compound 101. COMPOUND 91 was prepared according to the method described in Scheme 18, step 4 substituting N-(6-bromopyridin-2-yl)-2-phenylacetamide for N-(6- chloropyridin-3-yl)-2-phenylacetamide and <strong>[338454-14-1](1H-indazol-5-yl)boronic acid</strong> for (5- (4,4,5,5 -tetramethyl- 1,3 ,2-dioxaborolan-2-yl)indolin- 1 -yl)(o-tolyl)methanone.

Reference： [1]Patent: WO2014/145642,2014,A2 .Location in patent: Page/Page column 161; 162; 163

42
[ 338454-14-1 ]
N-(6-bromopyridin-2-yl)-2-phenylacetamide [ No CAS ]
C₂₈H₂₂N₄O₂ [ No CAS ]

Reference： [1]Patent: WO2014/145642,2014,A2

43
[ 338454-14-1 ]
4-[(4-benzylamino-6-chloropyrimidin-2-ylamino)methyl]cyclohexanecarboxylic acid amide [ No CAS ]
4-[4-benzylamino-6-(1H-indazol-5-yl)-pyrimidin-2-ylamino]methyl}cyclohexanecarboxylic acid amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 10443 - 10454

44
[ 338454-14-1 ]
[ 1609191-10-7 ]
N-(1-(5-(1H-indazol-5-yl)-1H-imidazol-2-yl)-7-(methylamino)-7-oxoheptyl)thiazole-5-carboxamide [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2016,vol. 7,p. 454 - 459

45
[ 338454-14-1 ]
3-(6-bromo-4-chloroquinolin-3-yl)acrylate [ No CAS ]
[ 98-16-8 ]
9-(1H-indazol-5-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one [ No CAS ]

Reference： [1]ACS Combinatorial Science,2017,vol. 19,p. 748 - 754

46
[ 338454-14-1 ]
C₁₀H₁₁ClN₄O [ No CAS ]
C₁₇H₁₆N₆O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
29.8%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In ethanol; toluene; for 24h;Inert atmosphere;	A mixture of compound 2 (20 mg, 0.08 mmol), <strong>[338454-14-1]1H-indazol-5-ylboronic acid</strong>(18 mg, 0.1 mmol) and Sodium bicarbonate solution (1M, 0.25 mL) in toluene (0.5 mL)and EtOH (0.15 mL) was added Pd(dppf)C12 (3.5 mg) under N2 and stirred at 120C for 24h. Then the mixture was diluted with water (5 mL) and extracted with ethyl acetate (10 x 3mL). The combined organic layers were washed with brine (10 mL), dried over Na2504 andconcentrated in vacuo to dryness. The residue was purified by Pre-HPLC(PE : EA=1 :1) toobtain 8 mg Example 1, yield in 29.8%. ?H NMR (CDC13, 4001V11{z): oe 8.74 (s, 1H), 8.41(d, 1H, J = 8.8Hz), 8.19 (s, 1H), 7.70 (s, 1H), 7.54 (d, 1H, J = 8.8Hz), 6.73-6.71 (m, 1H),6.69-6.67 (m, 1H), 4.16 (t, 4H, J= 4.8Hz), 3.91 (t, 4H, J= 4.8Hz). ESI-MS (M+H): 321.

Reference： [1]Patent: WO2017/219800,2017,A1 .Location in patent: Paragraph 0096; 0097

47
[ 338454-14-1 ]
[ 1023591-44-7 ]
C₂₁H₂₀N₆OS [ No CAS ]

Reference： [1]Nature,2018,vol. 557,p. 228 - 232

48
[ 338454-14-1 ]
5-bromo-6-phenylpyrazin-2-amine [ No CAS ]
5-(1H-indazol-5-yl)-6-phenylpyrazin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
17%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,4-dioxane; water; at 100℃; for 18h;	To a stirred solution of 5-bromo-6-phenylpyrazin-2-amine (0.1 g, 0.4 mmol, 1.0 eq.) and <strong>[338454-14-1](1H-indazol-5-yl)boronic acid</strong> (0.127 g, 0.44 mmol, 1.1 eq.) in dioxane (4 mL) was added Na2CO3 (0.085 g, 0.8 mmol, 2.0 eq.) and 1 mL water. The reaction was purged with N2 for 5 min. To this reaction mixture was added with Pd(dppf)Cl2.DCM complex (0.016 g, 5 mol %) and N2 was purged again for another 5 min. The reaction mixture was heated at 100 C. for 18 h. The reaction mixture was allowed to cool to RT and extracted using ethyl acetate (3*35 mL). The combined organic layers were washed (brine), dried (anhydrous Na2SO4) and concentrated under vacuum to get the solid residue which was purified by reversed phase column chromatography to get the desired product as off white solid (0.02 g, 17%) LCMS: 288 [M+1]+. 1H NMR: (400 MHz, DMSO-d6) delta 13.01 (br. S, 1H), 7.96 (d, J=5.26 Hz, 2H), 7.64 (s, 1H), 7.28-7.43 (m, 3H), 7.10-7.28 (m, 4H), 6.54 (br. S, 2H).

Reference： [1]Patent: US2019/23666,2019,A1 .Location in patent: Paragraph 0441; 0442; 0443

49
[ 338454-14-1 ]
6-bromo-7-phenyl-1H-1,8-naphthyridin-4-one [ No CAS ]
6-(3a,7a-dihydro-1H-indazol-5-yl)-7-phenyl-1,8-naphthyridin-4(1H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
3%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,4-dioxane; water; at 100℃; for 18h;Inert atmosphere;	To a stirred solution of 6-bromo-7-phenyl-1,8-naphthyridin-4(1H)-one (0.150 g, 0.5 mmol, 1.0 eq.) and <strong>[338454-14-1](1H-indazol-5-yl)boronic acid</strong> (0.146 g, 0.6 mmol, 1.2 eq.) in dioxane (4 mL) was added Na2CO3 (0.106 g, 1.0 mmol, 2.0 eq.) and 1 mL water. The reaction was purged with N2 for 5 min. To this reaction mixture was added with Pd(dppf)Cl2.DCM complex (0.021 g, 5 mol %) and N2 was purged again for another 5 min. The reaction mixture was heated at 100 C. for 18 h. The reaction mixture was allowed to cool to RT and extracted using ethyl acetate (3*25 mL). The combined organic layers were washed (brine), dried (anhydrous Na2SO4) and concentrated under vacuum to get the solid residue which was purified by reversed phase column chromatography to get the desired product as off white solid (0.005 g, 3%) LCMS: 339 [M+1]+1H NMR (400 MHz, DMSO-d6) delta 13.11 (br. s., 1H), 12.33 (br. s., 1H), 8.39 (s, 1H), 8.05 (br. s., 1H), 7.98 (br. s., 1H), 7.72 (s, 1H), 7.33-7.46 (m, 3H), 7.28 (d, J=7.02 Hz, 2H), 7.08 (d, J=8.33 Hz, 1H), 6.14 (d, J=7.45 Hz, 2H).

Reference： [1]Patent: US2019/23702,2019,A1 .Location in patent: Paragraph 0453-0455

50
[ 338454-14-1 ]
8-bromo-9-(4-[[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxy]-phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-ol [ No CAS ]
5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-6-(1H-indazol-5-yl)-8,9-dihydro-7H-benzo[7]annulen-2-ol [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2019

51
[ 688-74-4 ]
[ 1033818-69-7 ]
[ 338454-14-1 ]

Yield	Reaction Conditions	Operation in experiment
72%	With n-butyllithium; at -78 - 20℃; for 0.5h;Inert atmosphere;	(2) Add 5-bromo-1- (triisopropylsilyl) -1H-indazole (24.8 g) and tri-n-propyl borate (19.2 g, 0.1 mol) to the reaction as the intermediate products obtained in step (1). In the bottle, cool to minus 78 degrees under the protection of nitrogen, add 2.5M n-butyllithium solution (40 ml, 0.1 mol) dropwise, and maintain the reaction temperature around minus 78. After the dropwise addition, stir at room temperature for half an hour and slowly raise the temperature to minus minus At 20 degrees, 100 ml of an aqueous solution was added to quench the reaction system, 2M hydrochloric acid was used to adjust the pH to 5-6, and the mixture was extracted with ethyl acetate. After drying, the product was recrystallized to obtain 6.6 g.The yield of the target product indazole-5-boronic acid in this example is 72%.

Reference： [1]Patent: CN110642880,2020,A .Location in patent: Paragraph 0061-0063; 0067-0070

52
[ 338454-14-1 ]
[ 15164-44-0 ]
[ 1301189-01-4 ]