[ CAS No. 79762-54-2 ] {[proInfo.proName]}

Name: 79762-54-2|6-Bromo-1H-indazole|98%
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Quality Control of [ 79762-54-2 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 79762-54-2 ]

SDS Specification

Alternatived Products of [ 79762-54-2 ]

Product Details of [ 79762-54-2 ]

CAS No. :	79762-54-2	MDL No. :	MFCD03265457
Formula :	C₇H₅BrN₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	WMKDUJVLNZANRN-UHFFFAOYSA-N
M.W :	197.03	Pubchem ID :	17842471
Synonyms :

Calculated chemistry of [ 79762-54-2 ]

Physicochemical Properties

Num. heavy atoms :	10
Num. arom. heavy atoms :	9
Fraction Csp3 :	0.0
Num. rotatable bonds :	0
Num. H-bond acceptors :	1.0
Num. H-bond donors :	1.0
Molar Refractivity :	43.79
TPSA :	28.68 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.43 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.34
Log Po/w (XLOGP3) :	2.92
Log Po/w (WLOGP) :	2.33
Log Po/w (MLOGP) :	1.88
Log Po/w (SILICOS-IT) :	2.75
Consensus Log Po/w :	2.24

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.57
Solubility :	0.0534 mg/ml ; 0.000271 mol/l
Class :	Soluble
Log S (Ali) :	-3.18
Solubility :	0.129 mg/ml ; 0.000655 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.77
Solubility :	0.0337 mg/ml ; 0.000171 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.51

Safety of [ 79762-54-2 ]

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

Application In Synthesis of [ 79762-54-2 ]

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

Upstream synthesis route of [ 79762-54-2 ]
Downstream synthetic route of [ 79762-54-2 ]

[ 79762-54-2 ] Synthesis Path-Upstream 1~12

1
[ 57848-46-1 ]
[ 79762-54-2 ]

Yield	Reaction Conditions	Operation in experiment
89.1%	for 20 h; Reflux	2-Fluoro-4-bromobenzaldehyde (20.0 g, 98.5 mmol) was suspended in hydrazine hydrate (100 mL) and heated under reflux for 20 hours. Cooling to room temperature to produce a large number of precipitates,The precipitate was collected by filtration and washed with water, and dried to give the title compound (17.3 g, 89.1percent).
85%	With hydrazine In 1,2-dimethoxyethaneReflux	A solution of 2-fluoro-4-bromobenzaldehyde (5.09g, 25 mmol) was dissolved in glyme (25 mE) and slowlytreated over 10 minutes with anhydrous hydrazine (25 mE,0.8 mol, 32 eq.).11274] The resulting biphasic mixture was then held at reflux overnight. The reflux condenser was replaced with a short-path distillation head and about half the solvent distilled, at which time the reaction flask showed one phase and two phases were evident in the distillate. The undistilled residue was cooled and treated with water (25 mE), forming a white precipitate. This solid was collected by filtration, washed thoroughly with water, and dried in vacuo to give 6-bromoindazole (4.21 g, 85percent) as white crystals.
76%	at 125℃; for 3 h;	To a 100 mL round-bottomed flask was added hydrazine (30 mL, 832 mmol) and 4-bromo-2-fluorobenzaldehyde (4.69 g, 23 mmol). The solution was stirred at 125° C. for 3 hours. After cooling to ambient temperature, the solution was concentrated under reduced pressure. The solution was quenched by pouring it into a mixture of ice water (100 mL), and then extracting with EtOAc (3.x.100 mL). The organic layers were combined, dried over sodium sulfate, and filtered. The solution was evaporated to dryness, and adsorbed onto silica gel. The crude product was purified using column chromatography through a Redi-Sep.(R). pre-packed silica gel column (40 g), eluting with a gradient of 0percent to 100percent EtOAc in hexanes, to provide 6-bromo-1H-indazole (4.6 g, 18 mmol, 76percent yield). LCMS (M+H) 197.9 calc. for C₇H₅BrN₂197.0, ¹H NMR (400 MHz, CD₃OD): δ ppm 8.03 (s, 1H), 7.67-7.72 (2H, m), 7.24-7.26 (m, 1H).

Reference： [1] Patent: CN106146401, 2016, A, . Location in patent: Paragraph 0117; 0190; 0191
[2] Patent: US2015/368278, 2015, A1, . Location in patent: Paragraph 1273; 1274
[3] Journal of Organic Chemistry, 2006, vol. 71, # 21, p. 8166 - 8172
[4] Patent: US2007/173506, 2007, A1, . Location in patent: Page/Page column 48
[5] Organic Process Research and Development, 2011, vol. 15, # 3, p. 565 - 569
[6] Journal of Organic Chemistry, 2006, vol. 71, # 21, p. 8166 - 8172

2
[ 93777-26-5 ]
[ 79762-54-2 ]

Yield	Reaction Conditions	Operation in experiment
76%	With hydrazine hydrate In dimethyl sulfoxide at 120℃; for 21 h;	To a vigorously stirred solution of 5-bromo-2-fluorobenzaldehyde (40.6 g, 0.2 mol) in DMSO (80 mL) was added N₂H4-xH₂O (40 mL, 0.8 mol) dropwise over 15 min (slow addition to keep the reaction not too hot). The resulting yellow slurry was heated at 120 ⁰C (oil temp.) for 21 h. The whole mixture was transferred to a 1 L flask and cooled for 10 min in air before quenching with ice (300 mL) and ice- cold H₂O (100 mL). The resulting mixture was stirred for 30 min at it. Precipitated formed was collected by suction filtration, rinsed thoroughly with H₂O (100 mL x 2), 2 M HCl (100 mL x 2), H₂O (100 mL x 2), 0.5 M Na₂CO₃ (100 mL x 2), H₂O (100 mL x 2), dried in air for 1 h and under high vacuum for 2 days to give 6- bromo-lH-indazole (30.05 g, 76percent) as a light yellow solid. MS ESI 196.9 [M + H]⁺, calcd for [C₇H₅BrN₂ + H]⁺ 197.0.

Reference： [1] Patent: WO2009/79767, 2009, A1, . Location in patent: Page/Page column 84

3
[ 6967-12-0 ]
[ 79762-54-2 ]

Yield	Reaction Conditions	Operation in experiment
48%	Stage #1: With hydrogen bromide; sodium nitrite In water at 0℃; for 0.25 h; Stage #2: With copper(I) bromide In water at 20 - 80℃; for 1.5 h;	6-Aminoindazole (1.33 g, 10 mmol) was dissolved in 48percent hydrobromic acid (5 mL) and water (16 mL). To the resulting solution at 0° C. was added dropwise a solution of sodium nitrite (0.77 g, 11 mmol) in water (9 mL). The mixture was stirred at 0° C. for 15 min. Urea (0.40 g) was added to remove excess nitrous acid. After stirring for 10 min, this solution was added dropwise to a stirred mixture of copper(I) bromide (4.3 g, 30 mmol), 48percent hydrobromic acid (10 mL) and water (24 mL) at room temperature. The reaction mixture was heated at 75-80° C. for 1.5 h, cooled to room temperature, basified with concentrated ammonium hydroxide, and extracted with chloroform (4.x.30 mL). The combined extracts were dried over sodium sulfate and concentrated to provide the bromoindazole (0.96 g, 48percent) as a greenish yellow solid; ¹H NMR (500 MHz, DMSO-d₆) δ 13.16 (s, 1H), 8.09 (s, 1H), 7.67 (s, 1H), 7.74-7.72 (d, J=8.5 Hz, 1H), 7.25-7.23 (dd, J=8.5, 1.4 Hz, 1H).

Reference： [1] Patent: US2006/142307, 2006, A1, . Location in patent: Page/Page column 8

4
[ 39478-78-9 ]
[ 79762-54-2 ]

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 23, p. 6049 - 6053
[2] Journal of Medicinal Chemistry, 2017, vol. 60, # 10, p. 4458 - 4473
[3] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 11, p. 3177 - 3180
[4] Patent: EP1622569, 2015, B1,

5
[ 6967-12-0 ]
[ 12775-96-1 ]
[ 79762-54-2 ]

Yield	Reaction Conditions	Operation in experiment
16%	With hydrogen bromide; sodium nitrite In hexane; water; ethyl acetate	(i) 6-Bromo-1H-indazole Sodium nitrite (315 mg, 4.56 mmol) was added in 2 portions to an ice-cooled suspension of 6-aminoindazole (500 mg, 3.8 mmol) in water (0.4 mL) and hydrobromic acid (48percent, 1.8 mL). The reaction mixture was stirred for 10 minutes longer than required for the brown gas to disappear. Copper powder (35 mg, 0.55 mmol) was then added and the mixture heated gently until nitrogen evolution began. The reaction mixture was then alternately heated and cooled to control the rate of reaction. When nitrogen evolution ceased, the reaction mixture was heated at 90° C. for 30 minutes, cooled to room temperature, neutralized with aqueous sodium hydroxide and the product extracted into ethyl acetate. The organic layer was washed sequentially with water and brine, dried over sodium sulfate and the solvent removed in vacuo. Flash chromatography on silica gel (20-40percent ethyl acetate in hexane) yield the title product (119 mg, 16percent).

Reference： [1] Patent: US6380242, 2002, B1,

6
[ 593-56-6 ]
[ 57848-46-1 ]
[ 79762-54-2 ]

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 19, p. 4143 - 4147

7
[ 79762-54-2 ]
[ 74-88-4 ]
[ 590417-94-0 ]

Yield	Reaction Conditions	Operation in experiment
160 mg	With potassium hydroxide In methanol for 2.5 h; Reflux	[0411] 6-Bromoindazole (400 mg) was dissolved in methanol (10 mL). To this solution, potassium hydroxide (450 mg)was added followed by methyl iodide (0.50 mL) and the mixture was refluxed for 2.5 h. The reaction was cooled, dilutedwith diethyl ether, washed with water, brine, dried and concentrated. The product 6-bromo-1-methylindazole (160 mg)was separated from its isomer by Combiflash

Reference： [1] Patent: EP1622569, 2015, B1, . Location in patent: Paragraph 0411
[2] European Journal of Medicinal Chemistry, 2019, vol. 161, p. 533 - 542

8
[ 79762-54-2 ]
[ 74-88-4 ]
[ 590417-94-0 ]
[ 590417-95-1 ]

Reference： [1] Patent: WO2015/42397, 2015, A1, . Location in patent: Paragraph 000898
[2] Patent: WO2015/65937, 2015, A1, . Location in patent: Paragraph 000807

9
[ 79762-54-2 ]
[ 74-88-4 ]
[ 590417-94-0 ]
[ 590417-95-1 ]

Reference： [1] Patent: WO2015/42397, 2015, A1, . Location in patent: Paragraph 000898
[2] Patent: WO2015/65937, 2015, A1, . Location in patent: Paragraph 000807

10
[ 79762-54-2 ]
[ 68-12-2 ]
[ 669050-69-5 ]

Yield	Reaction Conditions	Operation in experiment
58%	Stage #1: With sodium hydride In tetrahydrofuran at 20℃; for 1 h; Stage #2: With sec.-butyllithium In tetrahydrofuran; hexane at -78℃; for 2.25 h; Stage #3: at 20℃;	To a suspension of 60 percent NaH (10.0 g, 0.24 mol) in THF (240 mL) was added a suspension of 6-bromo-lH-indazole (39.4 g, 0.2 mol) in THF (280 mL) dropwise over 45 min. After addition, the resulting mixture was stirred for 1 h at rt to give a dark red clear solution which was cooled to -78 ⁰C.5-BuLi (1.4 M in <n="86"/>hexane, 300 mL, 0.42 mol) was added dropwsie over 1 h. During this addition, additional THF (130 mL) was added to keep the mixture stirring. After the addition, the resulting mixture was stirred for 75 min at -78 ⁰C; DMF (90 mL) was added dropwise (note: reaction solidified upon addition of DMF, occasional warming was needed to keep the mixture stirring). The resulting mixture was stirred at it overnight and cooled to 0 ⁰C. Solid NH₄Cl and saturated NH₄Cl were added to quench the reaction and bring the pH to about 7. The product was extracted with EtOAc (800 mL + 200 mL +300 mL, 1.3 L in total) and the combined extracts were washed with H₂O (300 mL x 3) and dried (Na₂SO₄). Evaporation of the solvent gave a dark red solid which was triturated by EtOAc (4 times, the last filtrate was purified by flash chromatography) to give the title compound (16.96 g in total, 58percent) as yellow brown solid. ¹H NMR (400 MHz, DMSO-d6) δ 13.62 (s, IH, NH), 10.12 (s, IH, CHO), 8.23 (s, IH), 8.17 (s, IH), 7.93 (d, J = 8.4 Hz, IH), 7.59 (d, J = 8.4 Hz, IH); MS ESI 147.0 [M + H]⁺, calcd for [C₈H₆N₂O+ H]⁺ 147.0.

Reference： [1] Patent: WO2009/79767, 2009, A1, . Location in patent: Page/Page column 84-85

11
[ 79762-54-2 ]
[ 24424-99-5 ]
[ 877264-77-2 ]

Yield	Reaction Conditions	Operation in experiment
94%	With dmap; triethylamine In acetonitrile at 0 - 20℃; for 18 h;	a) 1,1 -dimethylethyl 6-bromo- lH-indazole- 1 -carboxylateA suspension of 6-bromo-lH-indazole (82.74 mmol), DMAP (16.55 mmol), and Et₃N (19.56 mL) in CH₃CN at 0 °C was treated with bis( 1,1 -dimethylethyl) dicarbonate (82.74 mmol) in CH₃CN over 15 min such that the internal temperature remained at 5 °C. The reaction mixture was warmed to room temperature and stirred for 18 h. The reaction was concentrated in vacuo and the residue purified by flash chromatography (7percentEtO Ac/petroleum ether) to afford the title compound (23.2 g, 94percent) as a solid.
94%	With dmap; triethylamine In acetonitrile at 5 - 20℃; for 18.25 h;	1 ,1 -Dimethylethyl 6-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 H-indazole-1 - carboxylate(a) 1 ,1 -Dimethylethyl 6-bromo-1 H-indazole-1 -carboxylateA suspension of 6-bromo-1 /-/-indazole (82.74 mmol), 4-(dimethylamino)pyridine (16.55 mmol), and triethylamine (19.56 ml.) in acetonitrile at 0 °C was treated with bis(1 , 1 - dimethylethyl) dicarbonate (82.74 mmol) in acetonitrile over 15 min such that the internal temperature remained at 5 °C. The reaction mixture was warmed to room temperature and stirred for 18 h. The reaction was concentrated in vacuo and the residue purified by flash chromatography (7percent ethyl acetate/petroleum ether) to afford the title product as a solid (23.2 g, 94percent).
63%	With dmap; triethylamine In acetonitrile at 0 - 20℃;	To a 0 °C solution of 6-bromo-lH-indazole (20 mmol), triethylamine (4 mL), and 4-(dimethylamino)pyridine (4 mmol) in acetonitrile (100 mL) was dropwise added bis( 1 , 1 -dimethylethyl) dicarbonate (20 mmol) in acetonitrile. The reaction mixture was then stirred at room temperature overnight. The mixture was concentrated in vacuo and the residue was purified by flash chromatography (10percent ethyl acetate/petroleum ether) to give the title product (63percent).

Reference： [1] Patent: WO2012/37298, 2012, A1, . Location in patent: Page/Page column 49
[2] Patent: WO2013/28445, 2013, A1, . Location in patent: Page/Page column 54; 55
[3] Patent: WO2011/66211, 2011, A1, . Location in patent: Page/Page column 71-72
[4] Patent: WO2016/57834, 2016, A1, . Location in patent: Paragraph 000198

12
[ 79762-54-2 ]
[ 73183-34-3 ]
[ 937049-58-6 ]

Yield	Reaction Conditions	Operation in experiment
100%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium acetate In N,N-dimethyl-formamide at 100℃; for 15 h; Inert atmosphere	A mixture of 6-bromo-1 /-/-indazole (700 mg; 3.55 mmol), 4,4,4',4',5,5,5',5'-octamethyl- 2,2'-bi(1 ,3,2-dioxaborolane) (1 .50 g; 5.91 mmol), Pd(dppf)CI₂- DCM (290 mg; 0.36 mmol) and KOAc (1 .04 g; 10.6 mmol) in DMF (20 mL) was stirred at 100°C for 15 hours under nitrogen. The mixture was concentrated in vacuo, suspended in EtOAc (30 mL), filtered through Celite, and concentrated to afford 866 mg (100percent) of the title compound as a brown semi-solid, which was used directly without further purification. LC-MS for Ci₃H₁₇BN₂O₂+H⁺ [M+H]⁺: calcd. 245.1 ; found: 245.0.
81%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium acetate In N,N-dimethyl-formamide at 100℃; Sealed tube; Inert atmosphere	A 6-bromo-lH-indazole (3.0 g, 15.2 mmol), bis(pinacolato)diboron (7.7 g, 30.4 mmol), potassium acetate (5.9 g, 60.9 mmol) in dry N,N-dimethylformamide (40 mL) were placed in a sealed tube under argon purge. The reaction mixture was degassed for a further 10 min with a slow stream of argon, at which point [ 1 , 1 '- bis(diphenylphosphino)ferrocene]palladium(II) chloride, complex with dichloromethane (0.3 g) was added. The reaction mixture was heated at 100°C overnight. After cooled to ambient temperature reaction mixture was filtered through Celite, washed with ethyl acetate and solvents were evaporated under reduced pressure. Crude product was purified by flash chromatography (silica gel; hexane/ethyl acetate 1 : 1) to give 6-(tetramethyl-l ,3,2-dioxaborolan-2-yl)-lH- indazole (3.0 g); yield 81percent. LC-MS (m/z) 244.9 (M+l).

Reference： [1] Patent: WO2015/140717, 2015, A1, . Location in patent: Page/Page column 87; 88
[2] Patent: WO2017/68064, 2017, A1, . Location in patent: Page/Page column 182
[3] Journal of Medicinal Chemistry, 2017, vol. 60, # 10, p. 4458 - 4473
[4] Patent: US2007/203143, 2007, A1, . Location in patent: Page/Page column 50
[5] RSC Advances, 2017, vol. 7, # 44, p. 27737 - 27746

[ 79762-54-2 ] Synthesis Path-Downstream 1~81

1
[ 79762-54-2 ]
[ 2344-83-4 ]
6-bromo-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	With dicyclohexylmethylamine In tetrahydrofuran at 20℃; for 3h;

Reference： [1]Luo, Guanglin; Chen, Ling; Dubowchik, Gene [Journal of Organic Chemistry, 2006, vol. 71, # 14, p. 5392 - 5395]

2
[ 79762-54-2 ]
[ 885521-88-0 ]

Yield	Reaction Conditions	Operation in experiment
92%	With iodine; potassium hydroxide; In N,N-dimethyl-formamide; at 20℃; for 3h;	To a solution of 6-bromo-IH-indazole (10 g, 50.8 mmol) in dry dimethylformamide (10 mL) was added 12 (28.3 g, 112 mmol) and KOH (6.83 g, 122 mmol) and the reaction mixture was stirred at roomtemperature for 3h. The reaction mixture was partitioned between ethyl acetate and a 1:1 mixture of aqueous saturated NaCI and saturated Na2S2O3. The aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried (Na2SO4) and concentrated under reduced pressure to give iodoindazole INT-5A (15.0 g, 46.4 mmol, 92%) as a solid. LCMS: calculated for [M+Hj: 323/325, found: 323/325.
92%	With iodine; potassium hydroxide; In N,N-dimethyl-formamide; at 30℃; for 1h;	A mixture of 6-bromo-lH-indazole (31.8 g, 161.4 mmol, 1.0 eq), KappaOmicronEta (27.1 g, 484.2 mmol, 3.0 eq) in DMF (200 mL) was added I2 (82.0 g, 322.8 mmol, 2.0 eq). The mixture was stirred at 30 C for 1 h. The reaction was poured into aqueous Na2S03 solution and stirred for 15 min. The resulting solid was collected to give 6-bromo-3-iodo-lH-indazole (48.0 g, 92%) as an off-white solid. LRMS (M+H+) m/z calculated 322.9, found 322.7 and 324.7.
89.8%	With iodine; potassium hydroxide; In N,N-dimethyl-formamide; at 0 - 20℃;	To a solution of 38-S1 (2.5 g, 12.8 mmol) and DMF (15 mL) was added KOH (1.62 g, 28.8 mmol) and iodine (4.86 g, 19.1 mmol) at 0 C. The reaction mixture was stirred at room temperature overnight, quenched by aqueous Na2S2O3 solution (5 mL), diluted with EtOAc, washed with 10% aqueous LiCl solution and brine, dried over Na2SO4, and concentrated to dryness. The remaining residue was purified by column chromatography on silica gel (eluted with PE/EtOAc = 30:1) to afford 38-S2 (3.70 g, 89.8% yield) as a white solid. LC/MS (ESI) m/z: 322 (M+H)+.

88%	With iodine; potassium hydroxide; In N,N-dimethyl-formamide; at 20℃; for 1h;	To a flask was added 6-bromo- lH-indazole (i-9a) (1.96 g, 10 mmol), KOH (1.68 g, 30 mmol) and DMF (60 mL), followed by the addition of I2 (5.08 g, 20 mmol) in portions. The reaction mixture was stirred at RT for 1 h. The mixture was diluted with H20, and the organic layer was separated. The aqueous layer was extracted with CH2C12 (3 * 50 mL). The combined organics were washed with H20, brine, dried over Na2S04, and concentrated. The residue was purified by column chromatograph (PE/EA=10/1) to afford 2.84 g (88%) of the title compound. LCMS (ESI) calc'd for C7H4BrIN2 [M+H]+: 322.86, found: 323. Step 2. Preparation of (6-bromo-3-iodo-lH-indazol-l-yl)(2-chloro-6-(trifluorom- ethyl)phenyl)methanone (i-9c). To a flask was added 6-bromo-3-iodo-lH-indazol e (i-9b) (3.22 g, 10 mmol), DMAP (1.22 g, 10 mmol), TEA (2.77 mL, 20 mmol) and DCM (50 mL), followed by the addition of 2-chloro-6-(trifluoromethyl) benzoyl chloride (2.61 g, 10 mmol) slowly. The reaction mixture was stirred at RT for 5 h. The mixture was diluted with H20, and the organic layer was separated. The aqueous layer was extracted with CH2C12 (3 x 50 mL), The combined organics were washed with H20, brine, dried over Na2S04, and concentrated. The residue was purified by column chromatograph (PE/EA=10/1) to afford 4.9 g (82 %) of the title compound. LCMS (ESI) calc'd for Ci5H6BrClF3IN20 [M+H] : 528.83, found: 529.
88%	With iodine; potassium hydroxide; In N,N-dimethyl-formamide; at 20℃; for 1h;	To a flask was added <strong>[79762-54-2]6-bromo-1H-indazole</strong> (i-9a) (1.96 g, 10 mmol), KOH (1.68 g, 30 mmol) and DMF (60 mL), followed by the addition of 12 (5.08 g, 20 mmol) in portions. The reaction mixture was stirred at room temperature for 1 h. The mixture was diluted with H20, and the organic layer was separated. The aqueous layer was extracted with CH2C12 (3 * 50 mL). The combined organics werewashed with H20, brine, dried over Na2SO4, and concentrated. The residue was purified by column chromatography (PE/EA=10/1) to afford 2.84 g (88%) of the title compound. LCMS (ESI) calc?d for C7H4BrIN2 [M+H]: 322.86, found: 323.
71.2%	With iodine; potassium carbonate; In N,N-dimethyl-formamide; at 65℃; for 10h;	Compound 4 (1.97 g, 10 mmol, 1.0 eq.) Was dissolved in DMF (20 mL),Potassium carbonate (2.7 g, 20 mmol, 2.0 eq.) Was added. I2 (5.0 g, 20 mmol, 2.0 eq.)It was dissolved in DMF (8 mL) and added dropwise to the reaction solution, and reacted at 65 C for 10 hours.After the reaction is monitored by TLC, the reaction solution is poured into insurance powder (5.0g) and potassium carbonate (2.0g)A white solid (80 mL) was precipitated.Stir for 30min and filter,Compound 5 was obtained as a white solid (2.3 g, 71.2%).
	With potassium hydroxide; iodine; In N,N-dimethyl-formamide; at 23℃; for 3h;	A mixture of <strong>[79762-54-2]6-bromo-1H-indazole</strong> (6-2, 2.0 g, 10.2 mmol, 1 equiv), iodine (5.67 g, 22.3 mmol, 2.20 equiv) and potassium hydroxide (1.37 g, 24.4 mmol, 2.40 equiv) in DMF (50 mL) was stirred at 23 C for 3 h. The reaction mixture was partitioned between a 1: 1 aqueous mixture of saturated sodium chloride solution and saturated sodium thiosulfate solution and ethyl acetate (2 x 100 mL). The combined organic layers were washed with water then brine, dried over sodium sulfate and concentrated to give 6-bromo-3-iodo-1H-indazole (6-3) as a tan solid. 1H NMR (500 MHz, CDCl3) delta 10.30 (br s, 1H), 7.69 (br s, 1H), 7.40 (d, 1H, J = 8.5 Hz), 7.36 (dd, 1H, / = 8.5, 1.5 Hz). LRMS tn/z (M+H + CH3CN) 323.0 found, 322.9 required.
		Example 1A6-bromo-3-iodo-1H-indazole; A solution of <strong>[79762-54-2]6-bromo-1H-indazole</strong> (10 g, 50.8 mmol, commercially available) in dioxane (200 ml) was treated with 3N aqueous NaOH (100 ml). The vigorously stirred mixture was treated with iodine (27.1 g, 107 mmol), added portionwise over 5 minutes then stirred for 60 minutes. The reaction was quenched with 200 ml of 20% citric acid solution, followed by 160 ml of saturated NaHSO3 solution, then partitioned between ethyl acetate and water. The organic extract was dried with MgSO4 and concentrated to a solid which was triturated with ether and pentane to afford the title compound.
1.45 g	With iodine; potassium hydroxide; In N,N-dimethyl-formamide; at 1 - 40℃; for 1h;	(1) Synthesis of 6-bromo-3-iodo-1H-indazole [36-1] (hereinafter referred to as a compound [36-1]) To a solution of <strong>[79762-54-2]6-bromo-1H-indazole</strong> (1.11 g) in N,N-dimethylformamide (10 mL) were added iodine (2.17 g) and potassium hydroxide (1.14 g), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was quenched with water, and extracted with chloroform. The obtained organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the titled compound (1.45 g) as a yellow solid. 1H-NMR (400 MHz, CDCl3) delta: 11.22 (1H, s), 7.71 (1H, s), 7.39-7.31 (2H, m).
	With iodine; sodium hydroxide; In 1,4-dioxane; at 20℃; for 1h;	[000178j To a stirred solution of <strong>[79762-54-2]6-bromo-1H-indazole</strong> 1 (60 g, 1 eq) and 3 N NaOH (600 mL) in 1,4-dioxane (1200 mL), Iodine (171 g, 2.2 eq) was added and stirred at room temperature for 1 h. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was quenched with 20% citric acid solution, saturated sodium bicarbonate solution and extracted with ethyl acetate (3 X 300 mL). Combined organic extracts were washed with brine, dried over anhydrous sodium sulfate and evaporated under reduced pressure to afford the crude compound 2. LCMS (mlz): 323.05 (M + 1).
0.51 g	With iodine; potassium hydroxide; In N,N-dimethyl-formamide; at 20℃; for 4h;	To a solution of compound 4 (0.5 g, 2.53 mmol, 1 eg.) in DMF (5 mL) was added KOH (0.284 g, 5.07 mmol, 2 eqs.). Now iodine (0.964 g, 3.79 mmol, 1 .5 eqs.) the reaction mixture was stirred at room temperature for 4 hrs. The progress of the reaction was monitored by tic taking 4 as a limiting reactant. After completion of reaction, the excess of solvent was dried under reduced pressure. The crude reaction mixture was purified via column chromatography using 20-25 % mixture of ethyl acetate in hexane as eluent to obtain 23 as pure compound (0.51 g).
1.5 g	With iodine; potassium hydroxide; In N,N-dimethyl-formamide; at 20 - 25℃; for 3h;	A mixture of 6-bromo-1 H-indazole (1 g) and Potassium hydroxide (0.570 g) in DMF (15 mL) was stirred at 0C and Iodine (1.93 g) was added. The mixture was stirred at ambient temperature for 3 h and Sodium thiosulphate solution (5 % in water) was subsequently added. The mixture was extracted with EtOAc and the extracts dried over anhydrous Sodium sulphate and evaporated invacuo and the residue obtained was subjected to silica gel flash column chromatography, eluting with a gradient of EtOAc and Heptane to obtain the title compound as a white solid (1.5 g). HPLC/MS (method 1): Rt : 1.89 min; m / z = 320.8 (M-1 )+; 1H NMR (500 MHz, DMSO-d6) d 13.68 (s, 1 H), 7.87 (s, 1 H), 7.45 (d, J = 8.6 Hz, 1 H), 7.38 (d, J = 8.6 Hz, 1 H).
		i: Compound 1 (1.0 eq) and potassium hydroxide solid (2.0 eq) were dissolved in DMF, stirred at room temperature, after completely dissolved, Iodine I2 was slowly added to the reaction flask, the reaction mixture last for 1-2 hours. After reaction was completed by TLC analysis, water was added to quench, and sodium thiosulfate was added to neutralize the excess I2 until the color of the reaction solution transformed from black to yellowish white. The precipitate was then filtered through a separator funnel and washed repeatedly several times, dried, then intermediate 2 was gained. The yield was 85%.

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 2361 - 2372
[2]Patent: WO2016/8590,2016,A1 .Location in patent: Page/Page column 59
[3]Patent: WO2018/229543,2018,A2 .Location in patent: Paragraph 00479
[4]Patent: WO2018/160891,2018,A1 .Location in patent: Page/Page column 548-549
[5]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 6049 - 6053
[6]Patent: WO2014/26327,2014,A1 .Location in patent: Page/Page column 61
[7]Patent: WO2014/28589,2014,A2 .Location in patent: Page/Page column 63
[8]Patent: CN110452176,2019,A .Location in patent: Paragraph 0121; 0125-0126
[9]Patent: WO2006/86255,2006,A2 .Location in patent: Page/Page column 71; 72
[10]Patent: US2011/281868,2011,A1 .Location in patent: Page/Page column 19
[11]Patent: EP2878594,2015,A1 .Location in patent: Paragraph 0532-0534
[12]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 4143 - 4147
[13]Patent: WO2016/57834,2016,A1 .Location in patent: Paragraph 000178; 000231; 000468
[14]Patent: WO2018/170517,2018,A1 .Location in patent: Page/Page column 60; 61
[15]Patent: WO2019/121159,2019,A1 .Location in patent: Page/Page column 86
[16]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29
[17]European Journal of Medicinal Chemistry,2020,vol. 187

3
[ 57848-46-1 ]
[ 79762-54-2 ]

Yield	Reaction Conditions	Operation in experiment
89.1%	With hydrazine hydrate; for 20h;Reflux;	2-Fluoro-4-bromobenzaldehyde (20.0 g, 98.5 mmol) was suspended in hydrazine hydrate (100 mL) and heated under reflux for 20 hours. Cooling to room temperature to produce a large number of precipitates,The precipitate was collected by filtration and washed with water, and dried to give the title compound (17.3 g, 89.1%).
85%	With hydrazine; In 1,2-dimethoxyethane;Reflux;	A solution of 2-fluoro-4-bromobenzaldehyde (5.09g, 25 mmol) was dissolved in glyme (25 mE) and slowlytreated over 10 minutes with anhydrous hydrazine (25 mE,0.8 mol, 32 eq.).11274] The resulting biphasic mixture was then held at reflux overnight. The reflux condenser was replaced with a short-path distillation head and about half the solvent distilled, at which time the reaction flask showed one phase and two phases were evident in the distillate. The undistilled residue was cooled and treated with water (25 mE), forming a white precipitate. This solid was collected by filtration, washed thoroughly with water, and dried in vacuo to give 6-bromoindazole (4.21 g, 85%) as white crystals.
76%	With hydrazine; at 125℃; for 3h;	To a 100 mL round-bottomed flask was added hydrazine (30 mL, 832 mmol) and 4-bromo-2-fluorobenzaldehyde (4.69 g, 23 mmol). The solution was stirred at 125 C. for 3 hours. After cooling to ambient temperature, the solution was concentrated under reduced pressure. The solution was quenched by pouring it into a mixture of ice water (100 mL), and then extracting with EtOAc (3×100 mL). The organic layers were combined, dried over sodium sulfate, and filtered. The solution was evaporated to dryness, and adsorbed onto silica gel. The crude product was purified using column chromatography through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 0% to 100% EtOAc in hexanes, to provide 6-bromo-1H-indazole (4.6 g, 18 mmol, 76% yield). LCMS (M+H) 197.9 calc. for C7H5BrN2 197.0, 1H NMR (400 MHz, CD3OD): delta ppm 8.03 (s, 1H), 7.67-7.72 (2H, m), 7.24-7.26 (m, 1H).

74%

With hydrazine hydrate; In 1,2-dimethoxyethane; at 170℃; for 8h;

4-bromo-2-fluorobenzaldehyde (2.03 g, 10 mmol) was dissolved in 10 mL of ethylene glycol dimethyl ether in a round bottom flask, followed by 10 mL of hydrazine hydrate, as shown in the above reaction equation.The reaction was carried out at 170 C for 8 hours.After completion of the reaction, the mixture was cooled to room temperature, and water was added to precipitate a solid. After filtration, the title compound was obtained in a yield of 74%.

Reference： [1]Patent: CN106146401,2016,A .Location in patent: Paragraph 0117; 0190; 0191
[2]Patent: US2015/368278,2015,A1 .Location in patent: Paragraph 1273; 1274
[3]Journal of Organic Chemistry,2006,vol. 71,p. 8166 - 8172
[4]Patent: US2007/173506,2007,A1 .Location in patent: Page/Page column 48
[5]Patent: CN110003171,2019,A .Location in patent: Paragraph 0140-0144
[6]Organic process research and development,2011,vol. 15,p. 565 - 569
[7]Journal of Organic Chemistry,2006,vol. 71,p. 8166 - 8172
[8]Journal of Medicinal Chemistry,2019,vol. 62,p. 6561 - 6574

4
[ 6967-12-0 ]
[ 79762-54-2 ]

Yield	Reaction Conditions	Operation in experiment
48%		6-Aminoindazole (1.33 g, 10 mmol) was dissolved in 48% hydrobromic acid (5 mL) and water (16 mL). To the resulting solution at 0 C. was added dropwise a solution of sodium nitrite (0.77 g, 11 mmol) in water (9 mL). The mixture was stirred at 0 C. for 15 min. Urea (0.40 g) was added to remove excess nitrous acid. After stirring for 10 min, this solution was added dropwise to a stirred mixture of copper(I) bromide (4.3 g, 30 mmol), 48% hydrobromic acid (10 mL) and water (24 mL) at room temperature. The reaction mixture was heated at 75-80 C. for 1.5 h, cooled to room temperature, basified with concentrated ammonium hydroxide, and extracted with chloroform (4×30 mL). The combined extracts were dried over sodium sulfate and concentrated to provide the bromoindazole (0.96 g, 48%) as a greenish yellow solid; 1H NMR (500 MHz, DMSO-d6) delta 13.16 (s, 1H), 8.09 (s, 1H), 7.67 (s, 1H), 7.74-7.72 (d, J=8.5 Hz, 1H), 7.25-7.23 (dd, J=8.5, 1.4 Hz, 1H).

Reference： [1]Patent: US2006/142307,2006,A1 .Location in patent: Page/Page column 8

5
5-bromo-2-methylphenyldiazonium tetrafluoroborate [ No CAS ]
[ 79762-54-2 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium acetate;18-crown-6 ether; In chloroform; at 23℃; for 20h;	A solution of sodium nitrite (4.08 g, 53.7 mmol, 1.10 equiv) in water (40 mL) was added slowly to a pre-cooled (-10 C) mixture of finely powdered 5-bromo-2-methylaniline (6-1, 10.0 g, 54.5 mmol, 1 equiv) and concentrated aqueous hydrochloric acid solution (12 M, 13.4 mL, 161 mmol, 3.00 equiv) in water (70 mL) at a rate that kept the reaction mixture temperature below 0 C. Following the addition, the reaction mixture was stirred at -5 C for 30 min, then filtered. A solution of sodium tetrafluoroborate (17.7 g, 161 mmol, 3.00 equiv) in water (50 mL) was immediately added to the cold filtrate. The precipitate was filtered and washed with ice-cold water (30 mL). The remaining solid was air-dried to give 5-bromo-2-methylbenzenediazonium tetrafluoroborate as a white solid. A suspension of this product (15.0 g, 52.7 mmol, 1 equiv), potassium acetate (12.9 g, 132 mmol, 2.50 equiv) and 18- crown-6 (1.39 g, 5.27 mmol, 0.100 equiv) in chloroform (300 mL) was stirred at 23 C for 20 h. The reaction mixture was filtered and concentrated. The residue was partitioned between water and EtOAc (500 mL). The organic layer was washed with brine, dried over sodium sulfate and concentrated to give 6-bromo-1H-indazole (6-2) as a tan solid. 1H NMR (300 MHz, CDCl3) delta 10.20 (br s, 1H), 8.06 (br s, 1H), 7.70 (s, 1H), 7.63 (d, 1H, J = 8.5 Hz), 7.29 (dd, 1H, J = 8.5, 1.5 Hz).
0.9 g	With 18-crown-6 ether; potassium acetate; In chloroform; at 20℃; for 2h;	[0410] 5-Bromo-2-methylphenyldiazonium tetrafluoroborate (1.50 g) was added to a mixture of potassium acetate (1.0g) and 18-crown-6 (70 mg) in chloroform (50 mL) at room temperature in portions and then the reaction was stirred for2 h. The resulting mixture was filtered and washed with chloroform. The filtrate was concentrated, and the residue wasdissolved in diethyl ether, which was then washed with water, brine, dried, and the solvent was removed to give theproduct 6-bromoindazole (0.9 g). The product was used in the next step without further purification

Reference： [1]Patent: WO2006/86255,2006,A2 .Location in patent: Page/Page column 71
[2]Patent: EP1622569,2015,B1 .Location in patent: Paragraph 0410

6
[ 79762-54-2 ]
[ 100-39-0 ]
[ 937046-99-6 ]

Yield	Reaction Conditions	Operation in experiment
62%	In 1,4-dioxane;Reflux;	6-Bromoindazole (3.63 g, 18 mmol) was suspended in dioxane (15 mE) and benzyl bromide (2.65 mE, 22 mmol, 1 .2 eq.) was added. The reaction was heated to reflux overnight, then allowed to cool to 80 C. after which point ethyl acetate (50 mE) added. The cake was broken up with a spatulaand afier stirring for 20 mm, the solids were filtered off and washed with ethyl acetate, giving glossy white crystals of the hydrobromide salt of 2-benzyl-<strong>[79762-54-2]6-bromoindazole</strong>. These were suspended in ethyl acetate (100 mE) and shaken with saturated NaHCO3 (150 mE) until dissolution. The layers were separated and the aqueous layer was extracted with ethyl acetate (50 mE). The combined organic layers were concentrated to an off-white powder which was recrystallized from 66% ethanol (40 mE). Washing with water and drying in vacuo gave 2-benzyl-<strong>[79762-54-2]6-bromoindazole</strong> (3.30 g, 62%) as shiny white plates.
61%		6-Bromoindazole (14.42 g, 73.2 mmol) was suspended in 50 mL of dioxane and the mixture was treated with benzyl bromide (10.5 mL, 88.8 mmol) and then heated in an oil bath to 120 0C with mechanical stirring overnight. The resulting thick suspension was allowed to cool to 80 0C (bath temp) and 200 mL of EtOAc was added. The mixture was vigorously stirred for 20 minutes and the precipitated orange-brown solid was collected by filtration, washed well with EtOAc and air-dried. The resulting brown solid was partitioned between sat aq. NaHCO3 (100 mL) and EtOAc (300 mL) with stirring until all of the solid material had dissolved. The layers were separated and the aqueous phase was extracted with 2 X 100 mL of EtOAc. The combined organic phases were washed with brine, dried and filtered and concentrated in vacuo to give a brown solid.Recrystallization of the solid from 200 mL of 2:1 EtOH:water gave 12.78 g (61%) of desired product as tan needles. 1H-NMR (DMSO-alphafe) beta 8.55 (s, 1 H), 7.84 (s, 1 H), 7.72 (d,1 H), 7.48 - 7.28 (m, 5H), 7.13 (d, 1 H), 5.62 (s, 2H); LC-MS [M+H]+ = 287.3, 289.0, RT =3.53 min.

Reference： [1]Patent: US2015/368278,2015,A1 .Location in patent: Paragraph 1275
[2]Patent: WO2007/56170,2007,A2 .Location in patent: Page/Page column 75

7
[ 79762-54-2 ]
[ 879014-17-2 ]
4-(6-bromo-1H-indazol-1-yl)-6,7-dimethoxycinnoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95.6%	With copper(l) iodide; potassium carbonate; N,N`-dimethylethylenediamine; In toluene; at 115℃; for 24h;	[00189] Step l. Into a 5 mL microwave tube was added 4-bromo-6,7- dimethoxycinnoline (250 mg, 0.743 mmol, prepared as described in Example 1 above), 6- <n="57"/>bromo-lH-indazole (219.1 mg, 1.112 mmol), copper(I) iodide (18 mg, 0.093 mmol), potassium carbonate (258.4 mg, 1.870 mmol), N,N'-dimethyl-l,2-ethanediamine (40 muL) and toluene (1 mL) The resulting dark, olive-green colored suspension was heated at 115 0C for 24 h. The crude product was purified by flash chromatography on silica gel (using a gradient of 50% ethyl acetate/hexanes to 100% hexanes) to give 0.342 g of 4-(6-bromo-lH-indazol-l- yl)-6,7-dimethoxycinnoline (95.6 % yield) which was used in the next step without further purification.

Reference： [1]Patent: WO2007/98214,2007,A1 .Location in patent: Page/Page column 55-56

8
[ 79762-54-2 ]
[ 73183-34-3 ]
[ 937049-58-6 ]

Yield	Reaction Conditions	Operation in experiment
100%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In N,N-dimethyl-formamide; at 100℃; for 15h;Inert atmosphere;	A mixture of 6-bromo-1 /-/-indazole (700 mg; 3.55 mmol), 4,4,4',4',5,5,5',5'-octamethyl- 2,2'-bi(1 ,3,2-dioxaborolane) (1 .50 g; 5.91 mmol), Pd(dppf)CI2- DCM (290 mg; 0.36 mmol) and KOAc (1 .04 g; 10.6 mmol) in DMF (20 mL) was stirred at 100C for 15 hours under nitrogen. The mixture was concentrated in vacuo, suspended in EtOAc (30 mL), filtered through Celite, and concentrated to afford 866 mg (100%) of the title compound as a brown semi-solid, which was used directly without further purification. LC-MS for Ci3H17BN2O2+H+ [M+H]+: calcd. 245.1 ; found: 245.0.
81%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In N,N-dimethyl-formamide; at 100℃;Sealed tube; Inert atmosphere;	A 6-bromo-lH-indazole (3.0 g, 15.2 mmol), bis(pinacolato)diboron (7.7 g, 30.4 mmol), potassium acetate (5.9 g, 60.9 mmol) in dry N,N-dimethylformamide (40 mL) were placed in a sealed tube under argon purge. The reaction mixture was degassed for a further 10 min with a slow stream of argon, at which point [ 1 , 1 '- bis(diphenylphosphino)ferrocene]palladium(II) chloride, complex with dichloromethane (0.3 g) was added. The reaction mixture was heated at 100C overnight. After cooled to ambient temperature reaction mixture was filtered through Celite, washed with ethyl acetate and solvents were evaporated under reduced pressure. Crude product was purified by flash chromatography (silica gel; hexane/ethyl acetate 1 : 1) to give 6-(tetramethyl-l ,3,2-dioxaborolan-2-yl)-lH- indazole (3.0 g); yield 81%. LC-MS (m/z) 244.9 (M+l).
62%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In dimethyl sulfoxide; at 90℃; for 16h;Inert atmosphere;	6-Bromoindazole (0.5 g, 2.54 mmol), bis(pinacolato)diboron (0.7 g, 2.79 mmol) and potassium acetate (0.7 g, 7.62 mmol) were dissolved in dimethyl sulfoxide (15 mL). After replaced with nitrogen for three times, Pd(dppf)Cl2?DCM (310 mg, 0.38 mmol) was added to the system, and heated to 90 C under nitrogen atmosphere to reflux for 16 hours. TLC monitored that the raw material disappeared, and product was formed. The reaction was cooled to room temperature, and ethyl acetate (25 ml) and water (25 ml) were added to dilute the reaction solution and filtered. The filter cake was soaked with ethyl acetate (15 mL) and discarded. The filtrate was separated, and the combined organic layer was concentrated to dry to provide crude product. The crude product was purified by silica gel column chromatography (ethyl acetate / hexane = 1/50 to 30) to give an off-white solid compound 1b (384 mg, purity 96.8%, yield 62.0%). MS m/z 245.1 [M+H]+.

With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl-formamide; at 100℃; for 18h;

A mixture of <strong>[79762-54-2]6-bromo-1H-indazole</strong> (1 g), bis(pinacolato)diboron (3.87 g), potassium acetate (2.49 g), dichloro(1,1'-bis(diphenylphosphino)ferrocene) palladium(II) (112 mg) in DMF (20 mL) was stirred at 100 C. for 18 hours, cooled and extracted with ethyl acetate. The extract washed with brine, dried (Na2SO4), filtered and concentrated. The concentrate was flash chromatographed on silica gel twice with 15% ethyl acetate/hexanes.

Reference： [1]Patent: WO2015/140717,2015,A1 .Location in patent: Page/Page column 87; 88
[2]Patent: WO2017/68064,2017,A1 .Location in patent: Page/Page column 182
[3]Journal of Medicinal Chemistry,2017,vol. 60,p. 4458 - 4473
[4]Patent: EP3553065,2019,A1 .Location in patent: Paragraph 0118-0119
[5]Journal of Medicinal Chemistry,2020,vol. 63,p. 2527 - 2546
[6]Patent: US2007/203143,2007,A1 .Location in patent: Page/Page column 50
[7]RSC Advances,2017,vol. 7,p. 27737 - 27746

9
[ 79762-54-2 ]
[ 824-94-2 ]
[ 1049651-40-2 ]

Yield	Reaction Conditions	Operation in experiment
56%		4. Synthesis of 1-(4-methoxybenzyl)-<strong>[79762-54-2]6-bromo-1H-indazole</strong> Into a 500 mL round-bottom flask was placed a solution of NaH (2.03 g, 84.58 mmol) in TIE (60 mL). This was followed by the addition of a solution of <strong>[79762-54-2]6-bromo-1H-indazole</strong> (5 g, 25.38 mmol) in THY (70 mL), which was added dropwise with stirring, while cooling to a temperature of 0 C. over a time period of 30 minutes. The resulting solution was allowed to react, with stirring, for 30 minutes while the temperature was maintained at 0 C. in a bath of H2O/ice. This was followed by the addition of a solution of 1-(chloromethyl)-4-methoxybenzene (5.17 g, 33.01 mmol) in DMF (20 mL), which was added dropwise with stirring, while cooling to a temperature of 0 C. over a time period of 30 minutes. The resulting solution was allowed to react, with stirring, for an additional 4 hours while the temperature was maintained at reflux in a bath of oil. The reaction progress was monitored by TLC (ethyl acetate/petroleum ether=1:2). The residue was dissolved in 70 mL of H2O. The resulting solution was extracted three times with 300 mL of ethyl acetate and the organic layers combined and dried over Na2SO4. A filtration was performed. The filtrate was concentrated by evaporation under vacuum using a rotary evaporator. The residue was purified by eluding through a column with a 1:50 ethyl acetate/petroleum ether solvent system. This resulted in 4.5 g (56%) of 1-(4-methoxybenzyl)-<strong>[79762-54-2]6-bromo-1H-indazole</strong> as a white solid.

Reference： [1]Patent: US2008/200471,2008,A1 .Location in patent: Page/Page column 34; 35

10
[ 110-87-2 ]
[ 79762-54-2 ]
[ 1158680-88-6 ]

Yield	Reaction Conditions	Operation in experiment
89%	With pyridinium p-toluenesulfonate; In dichloromethane; at 20℃; for 48h;	A 250-mL round-bottom flask equipped with a magnetic stir bar, a rubber septum, and a nitrogen inlet was charged with 6-bromo-lH-indazole (10 g, 50.7 mmol) and anhydrous dichloromethane (102 mL). To this solution, 3,4-dihydro-2H-pyran (23 mL, 253.8 mmol) was added in one portion at room temperature followed by addition of pyridinium /?-toluene sulfonate (1.28 g, 5 mmol). The resulting mixture was stirred at room temperature for 48 h. Upon completion by TLC (or LCMS), the reaction mixture was quenched with water and extracted with dichloromethane (3x100 mL). The combined organic extracts were washed with water (100 mL), washed with brine (50 mL), dried over sodium sulfate, filtered, concentrated, and purified by silica gel chromatography (0- 10% ethyl acetate in hexanes) to give the title compound as a pale yellow oil (12.7 g, 89%). 1H NMR (400 MHz, DMSO-d6): delta 8.14 (s, 1H), 8.04 (br, 1H), 7.75 (d, / = 8.4 Hz, 1H), 7.32 (dd, / = 8.6, 1.6 Hz, 1H), 5.88 (dd, / = 9.8, 2.6 Hz, 1H), 3.89-3.72 (m, 2H), 2.44-2.31 (m, 1H), 2.06- 1.91 (m, 2H), 1.80-1.68 (m, 1H), 1.60- 1.47 (m, 2H).
84%	With magnesium sulfate; toluene-4-sulfonic acid; In tetrahydrofuran;Reflux;	A mixture of 6-bromo-1 H-indazole (10.0 g, 0.051 mcI), DHP (8.57 g, 0.102 mcI), PTSA (1.75g, 10.2 mmcl) and MgSO4 (18.0 g, 0.153 mcI) in THF (50 mL) was heated to reflux and stirred overnight. The mixture was filtered. The filtrate was diluted with water (50 mL) and extracted with EtOAc (30 mL x 3). The combination organic layers were washed with sat. NaHCO3 aqueous and brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by silica column (PE: EtOAc = 40: 1)to give the desired compound (12.0 g,yield 84%) as a yellow solid.1H NMR (300 MHz, CDCI3): oe 7.99 (S, 1H), 7.80 (s, 1H), 7.58 (d, J 8.7 Hz, 1H), 7.30-7.26(m, 1H), 5.67(dd, J- 9.3, 2.7 Hz, 1H), 4.06-4.02 (m, 1H), 3.81-3.72 (m, 1H), 2.60-2.47(m,IH), 2.19-2.04(m, 2H), 1.81-1.64(m, 3H).LC-MS (mobile phase: from 90% water and 10% CH3CN to 5% water and 95% CH3CN in 4.0mm, purity is > 95%, Rt = 2.632 mm; MS Calcd.: 280; MS Found: 281 [M+H].
73%	With toluene-4-sulfonic acid; In tetrahydrofuran; at 60℃; for 12h;	To a mixture of 6-bromo- lH-indazole (CAS 79762-54-2) (750 mg, 3.83 mmol, 1.0 eq) in THF (15 mL), DHP (2.8 g, 7.66 mmol, 2.0 eq) and TsOH (132 mg, 0.77 mmol, 0.2 eq) were added. The mixture was stirred at 60 C for 12 h. The solvent was removed in vacuo. The residue was diluted with ethyl acetate (50 mL) and washed with H20 (10 mL x 3). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (PE/EA = 10/1) to give 6-bromo-l-(tetrahydro-2H-pyran-2-yl)- lH-indazole as a yellow solid. 783 mg, Y: 73%. ESI-MS (M+H)+: 281.1. 1H NMR (400 MHz, CDC13) delta: 7.92 (s, 1H), 7.72 (s, 1H), 7.51 (d, J = 8.8 Hz, 1H), 7.21 (dd, J = 8.4, 1.6 Hz, 1H), 5.60 (dd, J = 9.2, 2.8 Hz, 1H), 3.98- 3.95 (m, 1H), 3.72-3.65 (m, 1H), 2.48-2.45 (m, 1H), 2.10- 1.99 (m, 2H), 1.72-1.48 (m, 3H).

67%	With toluene-4-sulfonic acid; In tetrahydrofuran; at 60℃;	A mixture of compound C-13 (25 g, 126.84 mmol), 114 3,4-dihydro-2H-pyran (134.5 mL, 1471.5 mL) and 115 p-TSA (5.57 g, 29.18 mmol) was taken in 15 THF (700 mL) and heated at 60 C. overnight. The reaction mixture was poured into ice water and the aqueous phase was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and filtered. The filtrate was evaporated under reduced pressure and residue purified over silica gel (230-400) column (eluting with 1-2% ethyl acetate in 107 hexane) to give desired compound C-11 (23.5 g, 67% yield).
62%	With toluene-4-sulfonic acid; In dichloromethane; at 20℃; for 4h;	Added to the dried 250mL round bottom flask 1 (10.00g, 51.0mmol), p-TSA (1.75g, 10.2mmol) and methylene chloride (100.0mL), was slowly added dropwise DHP (8.56g, 102.0mmol), room temperature stirring 4.0h. After completion of the reaction, the reaction solution was diluted with 100.0mL of water, 200 mL of dichloromethane and extracted two times the combined organic phase was dried over anhydrous sodium sulfate, the solvent was spin-dry compound 2 (8.90g, 62%).
49%	With toluene-4-sulfonic acid; In tetrahydrofuran; for 3h;Reflux;	A mixture of 6-bromo-1H-indazole (10 g, 52 mmol), dihydropyran (5.5 g, 66 mmol) and(775 mg, 4.1 mmol) in THF (100 mL) was refluxed for 3 hours. The reaction mixturewas diluted with H20 (200 mL), extracted with EtOAc (150 mL x 2), dried over Na2SO4 and concentrated. The residue was purified by flash chromatography column (petroleum ether/EtOAc 15/1) to afford the title compound (7.0 g, 49%) as a light yellow solid. 1H NMR (400 MHz, CDCI3): 67.98 (s, 1H), 7.79 (s, 1H), 7.58 (d, J 8.4 Hz, 1H), 7.27 (d, J=8.4 Hz, 1 H), 5.66 (dd, J 9.2, 2.4 Hz, 1 H), 4.05-4.01 (m, 1 H), 3.78-3.72 (m, 1 H), 2.58- 2.48(m, IH), 2.17- 2.05 (m, 2H), 1.81-1.67 (m, 3H).

Reference： [1]Synlett,2009,p. 615 - 619
[2]Asian Journal of Chemistry,2011,vol. 23,p. 451 - 454
[3]Patent: WO2016/189011,2016,A1 .Location in patent: Page/Page column 100; 101
[4]Journal of Medicinal Chemistry,2015,vol. 58,p. 4888 - 4904
[5]Patent: WO2017/12576,2017,A1 .Location in patent: Page/Page column 143; 144
[6]Patent: WO2016/11390,2016,A1 .Location in patent: Page/Page column 217
[7]Patent: US2018/311255,2018,A1 .Location in patent: Paragraph 0261
[8]Chemistry and biodiversity,2019,vol. 16
[9]Patent: CN105524048,2016,A .Location in patent: Paragraph 0226; 0227
[10]Patent: WO2018/137593,2018,A1 .Location in patent: Page/Page column 91; 92

11
[ 79762-54-2 ]
[ 76513-69-4 ]
[ 894808-02-7 ]

Yield	Reaction Conditions	Operation in experiment
96%	With tetrabutylammomium bromide; potassium hydroxide; In dichloromethane; water; at 0℃; for 1h;	To a mixture of 50% KOH in water (3.4 mL) and DCM (20 mL) at 0C was added (2-(chloromethoxy)ethyl)trimethylsilane (2.03 g, 12.18 mmol), followed by addition of TBAB (100 mg). The mixture was stirred at 0C for 1 hr then concentrated under reduced pressure. The residue was partitioned between water and EtOAc. The orgainc layer was separated, washed with water and brine, dried over anhydrous Na2S04, and concentrated under reduced pressure. The residue was purified on column chromatography to give the desired product (3.2 g, 96% yiled) as brown oil. LC-MS: m/z 327 (M+H)+.
69%		Example 9. 2-(6-Cyclopropyl- 1 -methyl- 1 H-indazol-3 -yl)-5H-pyrrolo [2,3 -b]pyrazine-7-carboxylic acid [(R)- 2-(4-cyano-piperidin- 1 -yl)- 1 -cyclo ropyl-2-oxo-ethyl]-amideStep 16 -Bromo - 1 -(2 -trimethylsilanyl-ethoxymethyl)- 1 H-indazo leIn a round-bottomed flask 6-bromo-lH-indazole (0.70 g, 3.55 mmol) was dissolved in DMF (7.5 ml). The reaction mixture was cooled to 0C and sodium hydride (60% dispersion in mineral oil, 172 mg, 4.3 mmol) was added). The reaction mixture was warmed to room temperature and stirred for 30 min then cooled back to 0C and SEM-C1 (0.76 ml, 4.28 mmol) was slowly added. After the addition was complete, the ice bath was removed and the reaction mixture was warmed to room temperature. After 1.5 h the reaction was quenched with water and extracted with diethyl ether (2x). The combined organic layers were washed twice with water and once with brine then dried over sodium sulfate, filtered and concentrated. The residue waschromato graphed over silica gel with EtOAc/Hexanes (gradient 0-10% EtOAc) to give 802 mg (69%) of 6-bromo-l-(2-trimethylsilanyl-ethoxymethyl)-lH-indazole as a light yellow oil.
	With tetrabutylammomium bromide; potassium hydroxide; In dichloromethane; water;	6- bromo-lH-indazole (4.93 g, 25 mmol) was suspended/partialy dissolved in anhydrous DCM (100 ml). Then 5N aqueous KOH (6.00 ml, 30.0 mmol) was added, followed by SEM-C1 (5.32 ml, 30.0 mmol) and tetrabutylammonium bromide (0.806 g, 2.500 mmol). Continued stirring overnight. Diluted with water and partitioned. Washed organic twice more with water, dried over sodium sulfate, filtered and evaporated. Added DCM to the crude and filtered to recover a white solid and a slightly yellow filtrate. Evaporated the filtrate down to half volume and filtered again, then purified the filtrate as is by silica gel chromatography, eluting with (0404) EtOAc/hexanes to give both regioisomers separately. The desired regioisomer eluted before the undesired. H NMR (500 MHz, CDC13): delta 7.99 s, IH), 7.79 (s, IH), 7.61 (d, J=8.5 Hz, IH), 7.31(dd, J=8.5, 1.5 Hz, 1H), 5.71 (s, 2H), 3.54 (m, 2H), 0.90 (m, 2H), 0.04 (s, 9H). (0405) MS[M+H]+: 327, 329.

Reference： [1]Patent: WO2016/112088,2016,A1 .Location in patent: Paragraph 0465
[2]Synlett,2009,p. 615 - 619
[3]Patent: WO2013/30138,2013,A1 .Location in patent: Page/Page column 72; 73
[4]Patent: WO2019/74810,2019,A1 .Location in patent: Page/Page column 31; 32; 33

12
[ 79762-54-2 ]
[ 68-12-2 ]
[ 669050-69-5 ]

Yield	Reaction Conditions	Operation in experiment
58%		To a suspension of 60 % NaH (10.0 g, 0.24 mol) in THF (240 mL) was added a suspension of 6-bromo-lH-indazole (39.4 g, 0.2 mol) in THF (280 mL) dropwise over 45 min. After addition, the resulting mixture was stirred for 1 h at rt to give a dark red clear solution which was cooled to -78 0C.5-BuLi (1.4 M in <n="86"/>hexane, 300 mL, 0.42 mol) was added dropwsie over 1 h. During this addition, additional THF (130 mL) was added to keep the mixture stirring. After the addition, the resulting mixture was stirred for 75 min at -78 0C; DMF (90 mL) was added dropwise (note: reaction solidified upon addition of DMF, occasional warming was needed to keep the mixture stirring). The resulting mixture was stirred at it overnight and cooled to 0 0C. Solid NH4Cl and saturated NH4Cl were added to quench the reaction and bring the pH to about 7. The product was extracted with EtOAc (800 mL + 200 mL +300 mL, 1.3 L in total) and the combined extracts were washed with H2O (300 mL x 3) and dried (Na2SO4). Evaporation of the solvent gave a dark red solid which was triturated by EtOAc (4 times, the last filtrate was purified by flash chromatography) to give the title compound (16.96 g in total, 58%) as yellow brown solid. 1H NMR (400 MHz, DMSO-d6) delta 13.62 (s, IH, NH), 10.12 (s, IH, CHO), 8.23 (s, IH), 8.17 (s, IH), 7.93 (d, J = 8.4 Hz, IH), 7.59 (d, J = 8.4 Hz, IH); MS ESI 147.0 [M + H]+, calcd for [C8H6N2O+ H]+ 147.0.

Reference： [1]Patent: WO2009/79767,2009,A1 .Location in patent: Page/Page column 84-85

13
[ 93777-26-5 ]
[ 79762-54-2 ]

Yield	Reaction Conditions	Operation in experiment
76%	With hydrazine hydrate; In dimethyl sulfoxide; at 120℃; for 21h;	To a vigorously stirred solution of 5-bromo-2-fluorobenzaldehyde (40.6 g, 0.2 mol) in DMSO (80 mL) was added N2H4-xH2O (40 mL, 0.8 mol) dropwise over 15 min (slow addition to keep the reaction not too hot). The resulting yellow slurry was heated at 120 0C (oil temp.) for 21 h. The whole mixture was transferred to a 1 L flask and cooled for 10 min in air before quenching with ice (300 mL) and ice- cold H2O (100 mL). The resulting mixture was stirred for 30 min at it. Precipitated formed was collected by suction filtration, rinsed thoroughly with H2O (100 mL x 2), 2 M HCl (100 mL x 2), H2O (100 mL x 2), 0.5 M Na2CO3 (100 mL x 2), H2O (100 mL x 2), dried in air for 1 h and under high vacuum for 2 days to give 6- bromo-lH-indazole (30.05 g, 76%) as a light yellow solid. MS ESI 196.9 [M + H]+, calcd for [C7H5BrN2 + H]+ 197.0.

Reference： [1]Patent: WO2009/79767,2009,A1 .Location in patent: Page/Page column 84

14
[ 79762-54-2 ]
[ 1201645-07-9 ]
[ 1201645-12-6 ]

Yield	Reaction Conditions	Operation in experiment
45%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 100℃; for 0.5h;Inert atmosphere; Microwave irradiation;	To a solution of compound 34 (160 mg, 0.35 mmol) in DMF (5 mL) was added 6-bromo-lH- indazole (103 mg, 0.53 mmol), IM Na2CO3 (91 mg, 1.05 mmol, in 1.0 mL water) and Pd(PPh3)4 (39 mg, 0.035 mmol). The reaction mixture was protected with N2, and stirred under microwave for 30 min at 1000C. The mixture was diluted with water (10 mL), extracted with DCM (3X20 mL), washed with brine, dried over Na2SO4, filtered, and concentrated. The resulting residue was purified by column chromatography (DCM: Methanol 80: 1 to 60: 1) to give 35b, 2-(4-((6-(1H- indazol-6-yl) -3-nitroqumolin-4-yl)methyl)phenyl)-2-methylpropanenitrile (70 mg, 45%) as a light yellow solid

Reference： [1]Patent: WO2009/155527,2009,A2 .Location in patent: Page/Page column 194

15
[ 79762-54-2 ]
[ 92136-39-5 ]
[ 1204400-68-9 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 60℃; for 1h;	Method for svnthesising A.2c and A.2 d; Bromoindazole A.4q (1.50 g, 7.61 mmol), K2CO3 (2.60 g, 19.0 mmol), CuI (304 mg, 1.60 mmol) and Pd(PPh3)4 (1.76 g, 1.60 mmol) are taken up in DME/H2O (30 mL, 1 :1), combined with alkyne A.3b (1.18 g, 7.61 mmol) and stirred for 1 h at 600C. The solvent is removed, the reaction mixture is purified by column chromatography (cyclohexane/EtOAc, 10% to 70%) and A.2c-PG (HPLC-MS: tRet. = 1.78 min; MS(M+H)+ = 272; method LCMSBASl) is obtained.
	With potassium carbonate;copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 60℃; for 1h;	Method for svnthesising A.2c and A.2; d(Boc)HNk 1 h, 60 0C A.2C-PG A.2d-PGA.2c A.2*d; Bromoindazole A.4q (1.50 g, 7.61 mmol), K2CO3 (2.60 g, 19.0 mmol), CuI (304 mg, 1.60 mmol) and Pd(PPh3)4 (1.76 g, 1.60 mmol) are taken up in DME/H2O (30 mL, 1 :1), combined with alkyne A.3b (1.18 g, 7.61 mmol) and stirred for 1 h at 60C. The solvent is removed, the reaction mixture is purified by column chromatography (cyclohexane/EtOAc, 10% to 70%) and A.2c-PG (HPLC-MS: tRet. = 1.78 min; MS(M+H)+ = 272; method LCMSBASl) is obtained.

Reference： [1]Patent: WO2010/7116,2010,A2 .Location in patent: Page/Page column 86-87
[2]Patent: WO2010/7114,2010,A2 .Location in patent: Page/Page column 120-121

16
[ 79762-54-2 ]
[ 1978-37-6 ]
[ 1248590-81-9 ]

Yield	Reaction Conditions	Operation in experiment
98%	With RuPhos palladacycle; lithium hexamethyldisilazane; ruphos In tetrahydrofuran at 65℃; for 4h; Inert atmosphere; Sealed vial;

Reference： [1]Henderson, Jaclyn L.; Buchwald, Stephen L. [Organic Letters, 2010, vol. 12, # 20, p. 4442 - 4445]

17
[ 79762-54-2 ]
[ 375853-82-0 ]
[ 1332527-16-8 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 110℃; for 16h;Inert atmosphere;	STEP A: 4-(1H-Indazol-6-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester To a mixture of <strong>[79762-54-2]6-bromoindazole</strong> (2.0 g, 10.2 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (3.5 g, 11.2 mmol) and Pd(PPh3)4 (1.2 g, 1.0 mmol) under N2 were added 1,4-dioxane (80 mL), followed by addition of K2CO3 (2 M in H2O, 20 mL, 40 mmol). The resulting mixture was heated at 110 C. for 16 h, then cooled to room temperature. The resulting mixture was then treated with saturated Na2CO3 aqueous solution. The resulting mixture was extracted with EtOAc (3*). The combined extracts were washed with brine and then dried over Na2SO4. The resulting mixture was filtered, concentrated under reduced pressure, and the residue purified by flash chromatography on silica-gel (gradient eluent heptane to 60% EtOAc in heptane) to yield 4-(1H-indazol-6-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester as brownish foam solid.
1.2 g	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; at 120℃; for 6h;Inert atmosphere;	To a solution of compound 4 (2 g, 10.1 mmol, 1 eq) in dioxane (80 imL) was added successively compound 34 (4.08 g, 7.8 mmol, 1 .3 eq.) and 2 (M) solution of K2CO3 (5.12 g, 26 mmol, 3 eq). Degassing was done for 15min, and then Pd(PP i3)4 (0.3 g, 0.26 mmol, 0.05 eq) was added under inert atmosphere. The reaction mixture was heated at 120C for 6 hrs. Excess of solvent was removed under vacuum and the reaction mass was diluted with water and extracted with ethyl acetate (3 x 50 ml). Combined organic layers were washed with water (50 ml) followed by brine solution (50 ml). The organic layer thus obtained was dried over anhy Na2S04 and concentrated to get crude product. The crude product was purified via column chromatography using 25 % mixture of ethyl acetate in hexane as eluent to obtain 35 as pure compound (1 .2 g).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 4762 - 4767
[2]Patent: US2011/263559,2011,A1 .Location in patent: Page/Page column 54
[3]Patent: WO2018/170517,2018,A1 .Location in patent: Page/Page column 67; 68

18
[ 79762-54-2 ]
[ 24424-99-5 ]
[ 877264-77-2 ]

Yield	Reaction Conditions	Operation in experiment
94%	With dmap; triethylamine; In acetonitrile; at 0 - 20℃; for 18h;	a) 1,1 -dimethylethyl 6-bromo- lH-indazole- 1 -carboxylateA suspension of 6-bromo-lH-indazole (82.74 mmol), DMAP (16.55 mmol), and Et3N (19.56 mL) in CH3CN at 0 °C was treated with bis( 1,1 -dimethylethyl) dicarbonate (82.74 mmol) in CH3CN over 15 min such that the internal temperature remained at 5 °C. The reaction mixture was warmed to room temperature and stirred for 18 h. The reaction was concentrated in vacuo and the residue purified by flash chromatography (7percentEtO Ac/petroleum ether) to afford the title compound (23.2 g, 94percent) as a solid.
94%	With dmap; triethylamine; In acetonitrile; at 5 - 20℃; for 18.25h;	1 ,1 -Dimethylethyl 6-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 H-indazole-1 - carboxylate(a) 1 ,1 -Dimethylethyl 6-bromo-1 H-indazole-1 -carboxylateA suspension of 6-bromo-1 /-/-indazole (82.74 mmol), 4-(dimethylamino)pyridine (16.55 mmol), and triethylamine (19.56 ml.) in acetonitrile at 0 °C was treated with bis(1 , 1 - dimethylethyl) dicarbonate (82.74 mmol) in acetonitrile over 15 min such that the internal temperature remained at 5 °C. The reaction mixture was warmed to room temperature and stirred for 18 h. The reaction was concentrated in vacuo and the residue purified by flash chromatography (7percent ethyl acetate/petroleum ether) to afford the title product as a solid (23.2 g, 94percent).
63%	With dmap; triethylamine; In acetonitrile; at 0 - 20℃;	To a 0 °C solution of 6-bromo-lH-indazole (20 mmol), triethylamine (4 mL), and 4-(dimethylamino)pyridine (4 mmol) in acetonitrile (100 mL) was dropwise added bis( 1 , 1 -dimethylethyl) dicarbonate (20 mmol) in acetonitrile. The reaction mixture was then stirred at room temperature overnight. The mixture was concentrated in vacuo and the residue was purified by flash chromatography (10percent ethyl acetate/petroleum ether) to give the title product (63percent).

With sodium hydroxide; In 1,4-dioxane; at 20℃; for 0.5h;

[000198j To a stirred solution of 6-bromo-1H-indazole 1 (0.9 g, 1 eq)in 1,4-dioxane (20 mE), 2 M NaOH solution (2.5 mL) was added and stirred at room temperature followed by the addition of Boc anhydride (1.106 g, 2 eq) and stirred for 30 mm. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was quenched with water and extracted with ethyl acetate (2 X 50 mL). Combined organic extracts were washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel 100-200 mesh using 15percent EtOAc-hexane to afford the title compound 2. LCMS (mlz): 196.90 (M - Boc).

Reference： [1]Patent: WO2012/37298,2012,A1 .Location in patent: Page/Page column 49
[2]Patent: WO2013/28445,2013,A1 .Location in patent: Page/Page column 54; 55
[3]Patent: WO2011/66211,2011,A1 .Location in patent: Page/Page column 71-72
[4]Patent: WO2016/57834,2016,A1 .Location in patent: Paragraph 000198

19
[ 79762-54-2 ]
[ 24424-99-5 ]
[ 890839-29-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: dmap; triethylamine / acetonitrile / 18 h / 0 - 20 °C 2: triethylamine; potassium acetate / dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; palladium diacetate / 1,4-dioxane / 110 °C
	Multi-step reaction with 2 steps 1: dmap; triethylamine / acetonitrile / 18.25 h / 5 - 20 °C 2: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium acetate; palladium diacetate; triethylamine / 1,4-dioxane / 110 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/37298, 2012, A1
[2]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2013/28445, 2013, A1

20
[ 79762-54-2 ]
3-(4-bromophenyl)-4-[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4H-1,2,4-triazole [ No CAS ]
6-[4-(4-[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4H-1,2,4-triazol-3-yl)phenyl]-1H-indazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
23%		Example 776-[4-(4- [(35)- 1 -(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl} -4H- 1 ,2,4-triazol-3- yl)phenyl]- lH-indazoleA mixture of 3-(4-bromophenyl)-4-[(35)-l-(cyclopropylcarbonyl)-3- pyrrolidinyl]methyl}-4H-l,2,4-triazole (100 mg, 0.266 mmol), PdCl2(dppf) (22 mg, 0.027 mmol), ¾zs(pinacolato)diboron (70 mg, 0.276 mmol), and KOAc (100 mg, 1.019 mmol) in 1,4-dioxane (2 mL) was stirred at 100 C overnight. 6-Bromo-lH-indazole (55 mg, 0.279 mmol) and 2 M aq. K2C03 (1.0 mL) were added and the reaction mixture was stirred at 100 C for 72 h. The reaction mixture was cooled to room temperature and the 1,4- dioxane layer was filtered through a plug of Celite and Na2S04, rinsing with 1,4-dioxane (4 mL). The combined 1,4-dioxane layers were concentrated in vacuo and the residue was purified by reverse phase HPLC (10-70% CH3CN/water with 0.1% NH4OH) to afford the title compound (25 mg, 23%) as a solid. MS(ES)+ m/e 413.1 [M+H]+.

Reference： [1]Patent: WO2012/37298,2012,A1 .Location in patent: Page/Page column 98

21
[ 79762-54-2 ]
[ 1044767-99-8 ]
[ 1394120-80-9 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In N,N-dimethyl-formamide; oil; at 0 - 50℃;	Synthesis of 5-bromo-4-(6-bromo-1H-indazol-1-yl)pyrimidin-2-amine To a solution of 6-bromo-1H-indazole (1.01 eq) in DMF (50 mL) at 0 C. was added sodium hydride in oil (1.3 eq). The ice bath was removed after 10 minutes and the reaction mixture was stirred for 30 minutes before the addition of <strong>[1044767-99-8]5-bromo-4-chloro-pyrimidin-2-amine</strong> (5.2 g). The reaction was judged to be complete by LC-MS after heating overnight at 50 C. The crude reaction mixture was subsequently concentrated to dryness whereupon the product was triterated from by sonication from Methanol to afford 7 g of 5-bromo-4-(6-bromo-1H-indazol-1-yl)pyrimidin-2-amine (158-a) as a light orange solid. 1H NMR (400 MHz, DMSO-d6) delta 8.48 (s, 1H), 8.41 (d, J=1.3 Hz, 1H), 7.86 (d, J=8.5 Hz, 1H), 7.49 (dd, J=8.5, 1.6 Hz, 1H), 7.30 (s, 2H).

Reference： [1]Patent: US2012/214762,2012,A1 .Location in patent: Page/Page column 188-189

22
[ 79762-54-2 ]
[ 1400706-19-5 ]
[ 1400704-03-1 ]

Yield	Reaction Conditions	Operation in experiment
37%		A reaction vessel containing <strong>[79762-54-2]6-bromoindazole</strong> (141.9mg, 0.72mmol), Et3N (1.5ml), dichlorobis- (triphenylphosphine)palladium (II) (16.8mg, 0.024mmol), copper (I) iodide (9.2mg, 0.048mmol) and DMF (2ml) was sealed, degassed and flushed with nitrogen. The mixture was stirred at rt for 30 min. A solution of (S)-2-[(4,6-dimethyl-2-prop-2-ynylamino-pyrimidine-5-carbonyl)-amino]- 3-[(thiophene-2-carbonyl)-amino]-propionic acid methyl ester (200mg, 0.48mmol) in DMF (2ml) was added at rt. The reaction mixture was stirred at 47 C for 24 h. The mixture was cooled to rt and extracted with EtOAc. The combined organic extracts were washed with water and brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by flashchromatography with a 40-100% EtOAc in hexane gradient to give pure product (99.2mg, 37% yield). MS m/e 532.0 (M+H+).

Reference： [1]Patent: WO2012/123467,2012,A1 .Location in patent: Page/Page column 72; 73

23
[ 79762-54-2 ]
[ 2367-76-2 ]
[ 1453841-41-2 ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: 2,4,6-trifluorobromobenzene With isopropylmagnesium chloride In tetrahydrofuran at 0℃; for 1h; Inert atmosphere; Stage #2: With zinc(II) chloride In tetrahydrofuran at 0 - 20℃; for 1h; Inert atmosphere; Stage #3: 6-bromo-1H-indazole With methanesulfonic acid(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II); XPhos In tetrahydrofuran at 20℃; for 12h; Inert atmosphere;

Reference： [1]Yang, Yang; Oldenhuis, Nathan J.; Buchwald, Stephen L. [Angewandte Chemie - International Edition, 2013, vol. 52, # 2, p. 615 - 619][Angew. Chem., 2013, vol. 125, # 2, p. 643 - 647,5]

24
[ 79762-54-2 ]
[ 352-34-1 ]
[ 1426845-58-0 ]

Yield	Reaction Conditions	Operation in experiment
55%	With trans-N,N'-dimethyl-1,2-cyclohexyldiamine; caesium carbonate; In 1,4-dioxane; at 100℃;	Synthesis of 6-bro -l-(4-fluorophenyl)-lH-indazoleTo a solution of 6-bromo-lH-indazole (500 mg, 2.54 mmol) and l-fluoro-4- iodobenzene (845 mg, 3.81 mmol) in Dioxane (10 mL), Cs2C03 (2.07 g, 6.35 mmol), Cul (48 mg, 0.25 mmol) and trans - Nu,Nu' -dimethyl- 1,2-cyclohexanediamine (50 mg, 0.35 mmol) were added. The reaction mixture was stirred at 100 C overnight. The reaction mixture was filtered and the filtrate was concentrated. The residue was purified by column chromatography (PE : EtOAc = 20 : 1) to provide 6-bromo-l-(4-fluorophenyl)-lH-indazole (400 mg, yield: 55%).

Reference： [1]Patent: WO2013/34048,2013,A1 .Location in patent: Page/Page column 91

25
[ 79762-54-2 ]
[ 5029-67-4 ]
[ 1414886-52-4 ]

Yield	Reaction Conditions	Operation in experiment
75%	With copper(I) oxide; caesium carbonate; In dimethyl sulfoxide; at 100℃; for 24h;Inert atmosphere;	General procedure: The N-nucleophile (0.735mmol), Cu2O (0.0735mmol), Cs2CO3 (1.47mmol), DMSO (0.3mL) and heteroaryl halide (1.103mmol) were added to a reaction vial and a screw cap was fitted to it. The reaction mixture was stirred under air in a closed system at 100C for 24h. After cooling to room temperature, the mixture was diluted with dichloromethane and filtered through a pad of Celite. The combined organic extracts were dried over anhydrous Na2SO4 and the solvent was removed under reduced pressure. The crude product was purified by silica-gel column chromatography to afford the N-arylated product. The identity and purity of the products was confirmed by 1H, 13C NMR spectroscopic analysis and elemental analysis or mass spectroscopy.

Reference： [1]Tetrahedron,2013,vol. 69,p. 7279 - 7284

26
[ 79762-54-2 ]
[ 761446-44-0 ]
[ 1448429-59-1 ]

Yield	Reaction Conditions	Operation in experiment
68%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In water; N,N-dimethyl-formamide; at 80℃; for 18h;Inert atmosphere;	In a three-necked round bottom flask (50 ml) equipped with a condenser and magnetic stirring bar, Pd(PPh3)4 (11.6 mg,0.01 mmol) was added portion wise to a solution of the <strong>[79762-54-2]6-bromo-1H-indazole</strong> (6; 1.97 g, 10 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole (7; 2.50 g, 12 mmol), K2CO3(4.145 mg, 30 mmol) in DMF/H2O (4/1, 15 ml), and nitrogen was bubbled through the mixture for 5 min. Then, the mixture was stirred for 18 h at 80 C (LC-MS control), then cooled to r.t., H2O(10 ml) was added, and the mixture was extracted with CH2Cl2(3 30 ml). The org. layer was dried (1 g of Na2SO4), concentrated to obtain crude product, which was purified by FC with MeOH/CH2Cl2.

Reference： [1]European Journal of Medicinal Chemistry,2013,vol. 65,p. 112 - 118

27
[ 79762-54-2 ]
[ 956907-34-9 ]
[ 1448429-60-4 ]

Yield	Reaction Conditions	Operation in experiment
55%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In water; N,N-dimethyl-formamide; at 80℃; for 18h;Inert atmosphere;	General procedure: In a three-necked round bottom flask (50 ml) equipped with a condenser and magnetic stirring bar, Pd(PPh3)4 (11.6 mg,0.01 mmol) was added portion wise to a solution of the <strong>[79762-54-2]6-bromo-1H-indazole</strong> (6; 1.97 g, 10 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole (7; 2.50 g, 12 mmol), K2CO3(4.145 mg, 30 mmol) in DMF/H2O (4/1, 15 ml), and nitrogen was bubbled through the mixture for 5 min. Then, the mixture was stirred for 18 h at 80 C (LC-MS control), then cooled to r.t., H2O(10 ml) was added, and the mixture was extracted with CH2Cl2(3 30 ml). The org. layer was dried (1 g of Na2SO4), concentrated to obtain crude product, which was purified by FC with MeOH/CH2Cl2.

Reference： [1]European Journal of Medicinal Chemistry,2013,vol. 65,p. 112 - 118

28
[ 79762-54-2 ]
[ 1257997-17-3 ]
[ 1448429-61-5 ]

Yield	Reaction Conditions	Operation in experiment
65%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In water; N,N-dimethyl-formamide; at 80℃; for 18h;Inert atmosphere;	General procedure: In a three-necked round bottom flask (50 ml) equipped with a condenser and magnetic stirring bar, Pd(PPh3)4 (11.6 mg,0.01 mmol) was added portion wise to a solution of the <strong>[79762-54-2]6-bromo-1H-indazole</strong> (6; 1.97 g, 10 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole (7; 2.50 g, 12 mmol), K2CO3(4.145 mg, 30 mmol) in DMF/H2O (4/1, 15 ml), and nitrogen was bubbled through the mixture for 5 min. Then, the mixture was stirred for 18 h at 80 C (LC-MS control), then cooled to r.t., H2O(10 ml) was added, and the mixture was extracted with CH2Cl2(3 30 ml). The org. layer was dried (1 g of Na2SO4), concentrated to obtain crude product, which was purified by FC with MeOH/CH2Cl2.

Reference： [1]European Journal of Medicinal Chemistry,2013,vol. 65,p. 112 - 118

29
[ 79762-54-2 ]
[ 78191-00-1 ]
[ 189559-85-1 ]

Yield	Reaction Conditions	Operation in experiment
9%		A. l-(lH-indazol-6-yl)ethanone (24-a) [00303] To a solution of 6-bromo-lH-indazole (5.0 g, 25.4 mmol) in 40 mL THF was added dropwise n-BuLi (2.5M, 30mL, 76.2 mmol) at -65 C, and the mixture was stirred for 2 h. Then, N-methoxy-N-methylacetamide (2.9 g, 27.9 mmol) was added. The reaction mixture was stirred for another 2 h at -65 C, then quenched with 40 mL H20. The mixture was extracted with EtOAc (3 x 50 mL). The combined organic layers were washed with 100 mL brine, dried, and concentrated to dryness. The residue was purified by flash column chromatography (PE/EA=40/1) to give the title compound 24-a (370 mg, 9%) as a yellow solid. [M+H] Calc'd for C9H8N20, 161; Found, 161.

Reference： [1]Patent: WO2014/89364,2014,A1 .Location in patent: Paragraph 00302; 00303

30
[ 79762-54-2 ]
[ 192182-56-2 ]
[ 1610790-52-7 ]

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

31
[ 79762-54-2 ]
[ 557-21-1 ]
[ 141290-59-7 ]

Yield	Reaction Conditions	Operation in experiment
	With tris(dibenzylideneacetone)dipalladium⁽⁰⁾ chloroform complex; N,N,N,N,-tetramethylethylenediamine; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In N,N-dimethyl-formamide at 160℃; for 0.0833333h; Microwave irradiation;	LLLL.1 Step 1: Synthesis of 1H-indazole-6-carbonitrile A suspension of 6-bromo-1H-indazole (1.00 g, 5.08 mmol, 1.00 equiv), zinc cyanide (1.19 g,10.13 mmol, 2.00 equiv), XantPhos (880 mg, 1.52 mmol, 0.30 equiv), Pd2(dba)3.CHC13 (530 mg,0.51 mmol, 0.10 equiv) and [2-(dimethylamino)ethyl]dimethylamine (2 mL, 13.25 mmol, 2.60equiv) in N,N-dimethylformamide (8 mL, 20.40 equiv) was irradiated with microwave radiationfor 5 mm at 160 °C. The reaction was then quenched by 20 mL of water. The solid was collectedand washed with 3x20 mL of diethyl ether to give the title compound (1.2 g, crude) as a brown solid. LC-MS (ES, m/z): 144 [M+Hf, 185 [M+CH3CN].
880 mg	With tetrakis(triphenylphosphine) palladium⁽⁰⁾ In N,N-dimethyl-formamide at 100℃; for 4h; Inert atmosphere;	88.1 Step 1: Preparation of ‘H-indazole-6-carbonitrile To a stirred solution of 6-bromo-1H-indazole (1.0 g, 5.08 mmol) in N,N-dimethylformamide (12mL) was added zinc cyanide (595 mg, 5.08 mmol, 322 liL) and tetrakis(triphenylphosphine)palladium(0)(586 mg, 508 limol), and the mixture was degassed with nitrogen three times. The mixture heated at 100°C for 4 h under nitrogen. The reaction cooled to 20 00 water (15 mL) was added, and the reactionmixture was extracted with ethyl acetate (40 mL x 3). The combined organic extracts were washed with saturated aqueous sodium chloride solution (20 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give crude product. This was triturated with petroleum ether (30 mL) and dichloromethane (5 mL), and the mixture filtered. The filter cake was dried in vacuo to give 1 H-indazole5 6-carbonitrile (880 mg) as a yellow solid that was used directly without further purification. 1H NMR (400MHz, DMSO-d6) O 13.65 (br. s., 1H), 8.33-8.12 (m, 2H), 7.99 (d, J8.4 Hz, 1H), 7.88-7.80 (m, 1H).

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2015/25025, 2015, A1 Location in patent: Page/Page column 231
[2]Current Patent Assignee: YUMANITY THERAPEUTICS INC - WO2018/81167, 2018, A1 Location in patent: Page/Page column 183; 184

32
[ 79762-54-2 ]
[ 74-88-4 ]
[ 590417-94-0 ]
[ 590417-95-1 ]

Yield	Reaction Conditions	Operation in experiment
		[000898] To Compound 232A (10 g, 50.8 mmol) in THF (50 mL) was added sodium hydride (60percent in mineral, 2.2 g, 55.8 mmol) with ice bath cooling. The mixture was stirred at room temperature for 30 min. Methyl iodide (4.74 mL, 76.1 mmol) was added at room temperature. The reaction mixture was stirred at room temperature for 1 h, quenched with saturated aqueous ammonium chloride solution (30 mL), and extracted with ethyl acetate (100 mL x 3). The combined organic layers were washed with brine (200 mL), dried over anhydrous sodium sulfate, and concentrated. Purification with flash column chromatography on silica gel (ethyl acetate in petroleum ether, 10percent to 30percent v/v) gave Compound 232B and Compound 232C.
		[000807j To Compound 132A (10 g, 50.8 mmol) in THF (50 mL) was added sodium hydride (60percent in mineral, 2.2 g, 55.8 mmol) with ice bath cooling. The mixture was stirred at room temperature for 30 mm. Methyl iodide (4.74 mL, 76.1 mmol) was added at room temperature. The reaction mixture was stirred at room temperature for 1 h, quenched with saturated aqueous ammonium chloride solution (30 mL), and extracted with ethyl acetate (100 mL x 3). The combined organic layers were washed with brine (200 mL), dried over anhydrous sodium sulfate, and concentrated. Purification with flash column chromatography on silica gel (ethyl acetate in petroleum ether, 10percent to 30percent v/v) gave Compound 132B and Compound 132C. For Compound 132B: LC-MS (ESI) mlz: 211 [M+H] ?H-NMR (DMSOd 6, 400 MHz): 5 (ppm) 4.04 (s, 3H), 7.26 (dd, J= 8.8, 2.0 Hz, 1H), 7.72 (d, J= 8.4 Hz, 1H), 7.99 (s, 1H), 8.08 (d, J= 0.8 Hz, 1H). For Compound 132C: LC-MS (ESI) mlz: 211 [M+H] ?H-NMR (DMSO-d6, 400 MHz): 5 Qpm) 4.17 (s, 3H), 7.13 (dd, J 8.8, 2.0 Hz, 1H), 7.69 (d, J= 8.8 Hz, 1H), 7.85 (s, 1H), 8.41 (s, 1H).

Reference： [1]Patent: WO2015/42397,2015,A1 .Location in patent: Paragraph 000898
[2]Patent: WO2015/65937,2015,A1 .Location in patent: Paragraph 000807

33
[ 79762-54-2 ]
[ 100-43-6 ]
6-bromo-1-(2-(pyridin-4-yl)ethyl)-1H-indazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88.9%	With potassium phosphate; tetrabutylammomium bromide; In water; at 180℃; for 0.333333h;Microwave irradiation; Green chemistry;	General procedure: To a 10 mL glass microwave vial equipped with a magnetic stir bar was charged with a mixture of 1H-indazoles (0.5 mmol, 1 equiv), 2-vinylpyridine or 4-vinylpyridine (1.5 mmol, 3 equiv), Potassium phosphate (1 mmol, 2 equiv) and TBAB (20 mol %, 0.1 mmol) in water (2 mL). The mixture was heated to 180C as fast as possible in microwave oven, and stirred for 20 min at 180C. The resulting solution was cooled to temperature and extracted with EtOAc twice. The combined organic layer was washed with saturated salt water, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by gradient elution (PE/AcOEt for starting materials, PE/AcOEt/TEA = 100/50/3 for the pure N1 substituted products and PE/AcOEt/TEA = 20/20/1 for N2 substituted products).

Reference： [1]Tetrahedron Letters,2015,vol. 56,p. 4811 - 4814

34
[ 79762-54-2 ]
[ 74-88-4 ]
[ 590417-94-0 ]

Yield	Reaction Conditions	Operation in experiment
46%		Step 1: Preparation of 6-Bromo-1-methyl-1H-indazole To a solution of 6-bromo-1H-indazole (6.48 g, 32.9 mmol) in anhydrous tetrahydrofuran (80 mL) at 0 C. was added sodium hydride (60% in mineral oil, 1.39 g, 34.5 mmol). The reaction mixture was warmed to room temperature for 2 h, then iodomethane (18.68 g, 132 mmol) was added and reaction mixture stirred at room temperature for 3 h. The reaction mixture was diluted with water (300 mL) and extracted with ethyl acetate (100 mL*3). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, concentrated in vacuo. The crude residue was purified by column chromatography (silica, petroleum ether/ethyl acetate=4/1) to afford 6-bromo-1-methyl-1H-indazole (3.2 g, 15.2 mmol, 46%) as a yellow oil. LCMS (ESI) m/z: 211.1 [M+H]+.
160 mg	With potassium hydroxide; In methanol; for 2.5h;Reflux;	[0411] 6-Bromoindazole (400 mg) was dissolved in methanol (10 mL). To this solution, potassium hydroxide (450 mg)was added followed by methyl iodide (0.50 mL) and the mixture was refluxed for 2.5 h. The reaction was cooled, dilutedwith diethyl ether, washed with water, brine, dried and concentrated. The product 6-bromo-1-methylindazole (160 mg)was separated from its isomer by Combiflash
	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;	General procedure: 458 mg (2.0 mmol) of methyl 3-(bromomethyl) benzoate (6a) and 382 mg (2.0 mmol) 6-bromoindole (5a) were added into a 50 mL flask, then 5.0 mL anhydrous DMF and 1.38 g (10.0mmol) potassium carbonate were added. The mixture was stirred at room temperature overnight.TLC indicated no starting material remained and the reaction was quenched by adding 25 mLwater. The solution was extracted with ethyl acetate (30 mL ×3) or dichloromethane (30 mL ×3).The organic solvent was combined and evaporated, the product was purified by flash column chromatography using hexane : ethyl acetate (7:1) as eluent. 655.2 mg target compound obtainedas pale yellow oil, yield 95%.

Reference： [1]Patent: US2019/330198,2019,A1 .Location in patent: Paragraph 1174
[2]Patent: EP1622569,2015,B1 .Location in patent: Paragraph 0411
[3]European Journal of Medicinal Chemistry,2019,vol. 161,p. 533 - 542

35
[ 79762-54-2 ]
[ 83004-13-1 ]
6-bromo-2-(6-methylpyridin-2-yl)-2H-indazole [ No CAS ]
6-bromo-1-(6-ethylpyridin-2-yl)-1H-indazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
19%; 26%		The preparation of 6-bromo-l-(6-ethylpyridin-2-yl)-lH-indazole was the same as that of 6-bromo-l-(6-methylpyridin-2-yl)-lH-indazole. The mixture of 6-bromo-l-(6- ethylpyridin-2-yl)-lH-indazole and 6-bromo-2-(6-ethylpyridin-2-yl)-2H-indazole was purified by pre-TLC (PE/EA = 10/1) to give 41-02-0002 and 6-bromo-2-(6-ethylpyridin-2- yl)-2H-indazole. Rf value of 6-bromo-l-(6-ethylpyridin-2-yl)-lH-indazole is more than that of 6-bromo-2-(6-ethylpyridin-2-yl)-2H-indazole. 6-bromo-l-(6-ethylpyridin-2-yl)-lH-indazole, 230 mg, as a yellow solid, Y: 26percent. ESI-MS (M+H)+: 302.0, 304.0. 6-bromo-2-(6-ethylpyridin-2-yl)-2H-indazole, 170 mg, as a yellow solid, Y: 19percent. ESI-MS (M+H)+: 302.0, 304.0.

Reference： [1]Patent: WO2016/11390,2016,A1 .Location in patent: Page/Page column 195

36
[ 79762-54-2 ]
[ 1037223-35-0 ]
6-bromo-1-(6-isopropylpyridin-2-yl)-1H-indazole [ No CAS ]
6-bromo-2-(6-isopropylpyridin-2-yl)-2H-indazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
23%; 21%		The preparation of 6-bromo-l-(6-isopropylpyridin-2-yl)-lH-indazole was the same as that of 6-bromo-l-(6-methylpyridin-2-yl)-lH-indazole. The mixture of 6-bromo-l-(6- isopropylpyridin-2-yl)-lH-indazole and 6-bromo-2-(6-isopropylpyridin-2-yl)-2H-indazole was purified by pre-TLC (PE/EA = 10/1) to give 6-bromo-l-(6-isopropylpyridin-2-yl)-lH- indazoleand 6-bromo-2-(6-isopropylpyridin-2-yl)-2H-indazole. Rf value of 6-bromo-l-(6- isopropylpyridin-2-yl)-lH-indazole is more than that of 6-bromo-2-(6-isopropylpyridin-2-yl)- 2H-indazole. 6-bromo-l-(6-isopropylpyridin-2-yl)-lH-indazole, 200 mg, as a yellow solid, Y: 23%. ESI-MS (M+H)+: 316.0, 318.0. 6-bromo-2-(6-isopropylpyridin-2-yl)-2H-indazole, 180 mg, as a yellow solid, ESI-MS (M+H)+: 316.0, 318.0.

Reference： [1]Patent: WO2016/11390,2016,A1 .Location in patent: Page/Page column 197; 198

37
[ 79762-54-2 ]
[ 7238-61-1 ]
2-(6-bromo-1H-indazol-1-yl)-4-methylthiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
32%	With sodium hydride; In N,N-dimethyl-formamide; at 130℃; for 12h;	The preparation of 2-(6-bromo-lH-indazol-l-yl)-4-methylthiazole was the similar to that of 6-bromo-l-(6-methylpyridin-2-yl)-lH-indazole. 200 mg, as a brown solid, Y: 32%. ESI-MS (M+H)+: 294.0. 1H NMR (400 MHz, CDC13) delta: 8.78 (s, 1H), 8.06 (s, 1H), 7.55 (d, J = 8.5 Hz, 1H), 7.36 (dd, J = 8.5, 1.5 Hz, 1H), 6.55 (s, 1H), 2.42 (s, 3H).

Reference： [1]Patent: WO2016/11390,2016,A1 .Location in patent: Page/Page column 213

38
[ 79762-54-2 ]
[ 41731-23-1 ]
2-(6-bromo-1H-indazol-1-yl)-5-methylthiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
33%	With sodium hydride; In N,N-dimethyl-formamide; at 130℃; for 12h;	The preparation of 2-(6-bromo-lH-indazol-l-yl)-5-methylthiazole was the similar to that of 6-bromo-l-(6-methylpyridin-2-yl)-lH-indazole. 200 mg, as a brown solid, Y: 33%. ESI-MS (M+H)+: 294.0. 1H NMR (400 MHz, CDC13) delta: 8.81 (s, 1H), 8.11 (s, 1H), 7.62 (d, J = 8.5 Hz, 1H), 7.42 (dd, J = 8.5, 1.6 Hz, 1H), 7.26 (s, 1H), 2.48 (d, J = 1.2 Hz, 3H).

Reference： [1]Patent: WO2016/11390,2016,A1 .Location in patent: Page/Page column 215

39
[ 79762-54-2 ]
[ 131747-45-0 ]
(4-(6-bromo-1H-indazol-1-yl)pyridin-2-yl)methanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
32%	With potassium phosphate; copper(l) iodide; trans-N,N'-dimethylcyclohexane-1,2-diamine; In 1,4-dioxane; at 100℃; for 16h;	A mixture of 6-Bromo-lH-indazole (CAS No. 79762-54-2, 1.5 g, 7.6 mmol, 1.0 eq), 4- Bromo-2-pyridinemethanol (CAS No. 131747-45-0, 1.85 g, 9.9 mmol, 1.3 eq), Cul (285 mg, 1.5 mmol, 0.2 eq), K3P04 (3.2 g, 15.2 mmol, 2.0 eq) and 61798-24-1 (426 mg, 3.0 mmol, 0.4 eq) in 1,4-dioxane (15 mL) was stirred at 110 C for 16 h. After concentration, the residue was purified by silica gel chromatography using PE/EA (3/1) as eluent to give (4-(6-bromo- lH-indazol-l-yl)pyridin-2-yl)methanol as a yellow solid. 750 mg, Y: 32%. ESI-MS (M+H)+: 304.1

Reference： [1]Patent: WO2016/11390,2016,A1 .Location in patent: Page/Page column 316

40
[ 79762-54-2 ]
[ 40155-34-8 ]
methyl 6-(6-bromo-1 H-indazol-1-yl)pyrazine-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
36%	With potassium phosphate; trans-N,N'-dimethylcyclohexane-1,2-diamine; copper(I) bromide; In toluene; at 110℃; for 16h;	The preparation of methyl 6-(6-bromo-lH-indazol-l-yl)pyrazine-2-carboxylate was similar to that of (6-(4-bromo-6-((4-methoxybenzyl)oxy)- lH-indazol- l-yl)pyridin-2-yl)methanol (Example 352, Step 4) to give 1.1 g as a yellow solid, Y: 36%. ESI-MS (M+H)+: 333.0. 1H NMR (400 MHz, CDC13) delta: 9.61 (s, 1H), 9.21 (s, 1H), 9.17 (s, 1H), 8.28 (s, 1H), 7.71 (d, J = 8.4 Hz, 1H), 7.52 (dd, J = 8.4, 1.2 Hz, 1H), 4.15 (s, 3H).
36%	With potassium phosphate; copper(l) iodide; cis-N,N'-dimethyl-1,2-diaminocyclohexane; In toluene; at 110℃; for 16h;	A mixture of <strong>[79762-54-2]6-bromo-1H-indazole</strong> (79762-54-2) (3.2 g, 16.3 mmol, 1.0 eq), (6-bromopyridin-2-yl)methanol (33674-96-3) (3.66 g, 19.6 mmol, 1.2 eq), CuT (620 mg, 3.26 mmol,0.2 eq), K3P04 (6.9 g, 32.6 mmol, 2.0 eq) and N,N?-Dimethyl-cyclohexane-1,2-diamine (61798-24-1) (930 mg, 6.52 mmol, 0.4 eq) in 1,4-dioxane (50 mL) was stirred at 110C for 16 h. After concentration, the residue was purified by silica gel chromatography using PE/EA (3/1) as eluent to give (6-(6-bromo-1H-indazol-1-yl)pyridin-2-yl)methanol;_The preparation of methyl 6-(6-bromo- 1 H-indazol- 1 -yl)pyrazine-2-carboxylate was similar to that of (6-(6-bromo-1H-indazol-1-yl)pyridin-2-yl)methanol (Example 1, Step 7) togive 1.1 g as a yellow solid, Y: 36%. ESI-MS (M+H): 333.0. ?H NMR (400 MHz, CDC13) (5:9.61 (s, 1H), 9.21 (s, 1H), 9.17 (s, 1H), 8.28 (s, 1H), 7.71 (d, J= 8.4 Hz, 1H), 7.52 (dd, J= 8.4,1.2 Hz, 1H), 4.15 (s, 3H).

Reference： [1]Patent: WO2016/11390,2016,A1 .Location in patent: Page/Page column 312
[2]Patent: WO2017/127430,2017,A1 .Location in patent: Page/Page column 28; 45

41
[ 79762-54-2 ]
[ 149849-94-5 ]
methyl 2-(6-bromo-1H-indazol-1-yl)pyrimidine-4-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
59%		To a solution of 6-bromo-lH-indazole (Cas No. 79762-54-2, 400 mg, 2.04 mmol, 1.0 eq) in DMF (6 mL) was added NaH (90 mg, 2.24 mmol, 1.1 eq) at 0 C. After stirring at 0 C for 15 min, Methyl 2-chloropyrimidine-4-carboxylate (CAS No. 149849-94-5, 352 mg, 2.04 mmol, 1.0 eq) dissolving in DMF (2 mL) was added and the reaction mixture was stirred at 0 C for 1 h. The reaction mixture was poured into H20 (40 mL) and stirred at rt for 15 min. The precipitate was collected by filtration and dried to give methyl 2-(6-bromo-lH-indazol-l- yl)pyrimidine-4-carboxylate. 400 mg, as a yellow solid, Y: 59%. ESI-MS (M+H)+: 333.0.
59%		To a solution of 6-bromo-1H-indazole (Cas No. 79762-54-2, 400 mg, 2.04 mmol, 1.0 eq) in DMF (6 mL) was added NaH (90 mg, 2.24 mmol, 1.1 eq) at 0C. After stirring at 0C for 15 mm, Methyl 2-chloropyrimidine-4-carboxylate (CAS No. 149849-94-5, 352 mg, 2.04 mmol, 1.0eq) dissolved in DMF (2 mL) was added and the reaction mixture was stirred at 0 C for 1 h. The reaction mixture was poured into H20 (40 mL) and stirred at ft for 15 mm. The precipitate was collected by filtration and dried to give methyl 2-(6-bromo-1H-indazol-1-yl)pyrimidine-4- carboxylate. 400 mg, as a yellow solid, Y: 59%. ESI-MS (M+H): 333.0.

Reference： [1]Patent: WO2016/11390,2016,A1 .Location in patent: Page/Page column 324
[2]Patent: WO2017/127430,2017,A1 .Location in patent: Page/Page column 42; 43

42
[ 79762-54-2 ]
[ 758699-74-0 ]
6-(4-methoxypyridin-3-yl)-1H-indazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); potassium carbonate; In 1,4-dioxane; water; at 110.0℃;	A mixture of 6-bromo-lH-indazole (500 mg, 2.54 mmol), 4-methoxy-3-(4,4,5,5-tetramethyl- l,3,2-dioxaborolan-2-yl)pyridine (895 mg, 3.81 mmol), Pd(dppf)C12 (414 mg, 0.51 mmol) and K2C03 (701 mg, 5.08 mmol) in dioxane (10 mL) and water (0.5 mL) was heated tol lO C and stirred overnight. The filtration removed the solid. After washing with DCM, the combined filtrate was concentrated in vacuo. The residue was purified by ISCO flash chromatography (eluted with 0-100% EtOAc / hexane) to provide 6-(4-methoxypyridin-3-yl)-lH-indazole.

Reference： [1]Patent: WO2016/36586,2016,A1 .Location in patent: Page/Page column 40; 41

43
[ 79762-54-2 ]
[ 758699-74-0 ]
4-(4-(6-(4-methoxypyridin-3-yl)-1H-indazol-1-yl)pyridin-2-yl)morpholine [ No CAS ]

Reference： [1]Patent: WO2016/36586,2016,A1

44
[ 79762-54-2 ]
[ 134419-59-3 ]
6-bromo-1-(tetrahydro-2H-pyran-4-yl)-1H-indazole [ No CAS ]
C₁₂H₁₃BrN₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%	With tetra-(n-butyl)ammonium iodide; potassium carbonate; In N,N-dimethyl-formamide; at 120℃; for 14h;	Intermediate R15 6-Bromo-l-(tetrahydro-2H-pyran-4-yl)-lH-indazole To a solution of 6-bromo-lH-indazole (200 mg, 1.015 mmol) in DMF (10 mL) was added <strong>[134419-59-3]tetrahydro-2H-pyran-4-yl methanesulfonate</strong> (274 mg, 1.523 mmol), TBAI (37.5 mg, 0.102 mmol) and K2CO3 (351 mg, 2.54 mmol). The reaction mixture was heated at 120 C for 14 h. The mixture was cooled to room temperature, diluted with EtOAc (20 mL), and washed with H2O (20 mL). The orange organic layer was washed with brine, dried over with MgS04, then concentrated to give crude product, which was purified by flash chromatography on silica gel eluting with 0-100% EtOAc/hexane (12 g column, 16 min gradient) to afford two regioisomers. 6-Bromo-l-(tetrahydro-2H-pyran- 4-yl)-lH-indazole (114 mg, 40% yield). LCMS (M+H)+ = 281.15. NMR (500 MHz, CDCb) delta 2.27 (m, 4H), 3.62 (m, 2H), 4.19 (m, 2H), 4.66 (m, 1H), 7.19 (dd, 1H), 7.56 (dd, 1H), 7.9 l(s, 1H), 7.98 (s, 1H).

Reference： [1]Patent: WO2016/64958,2016,A1 .Location in patent: Page/Page column 62

45
[ 79762-54-2 ]
[ 1083326-75-3 ]
N-(5-(1H-indazol-6-yl)-2-methoxypyridin-3-yl)methanesulfonamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 7239 - 7251

46
[ 79762-54-2 ]
[ 773-64-8 ]
6-bromo-1-(2,4,6-trimethylbenzenesulfonyl)indazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92.6%		0 C,To a solution of <strong>[79762-54-2]6-bromoindazole</strong> (7.35 g, 37.3 mmol) in tetrahydrofuran (100 mL) was added potassium tert-butoxide (3.65 g, 38.1 mmol) and stirred for 30 minutes.2,4,6-trimethylbenzenesulfonyl chloride (8.35 g, 38.1 mmol) was added in one portion to the reaction system and stirred at room temperature for 40 minutes.The reaction was quenched with saturated aqueous ammonium chloride and extracted with ethyl acetate.The organic phase was washed with saturated brine,Dried over anhydrous sodium sulfate, and concentrated to give the title compound (13.1 g, 92.6%).

Reference： [1]Patent: CN106146401,2016,A .Location in patent: Paragraph 0192; 0193

47
[ 79762-54-2 ]
C₅H₁₃ClOSi [ No CAS ]
[ 894808-02-7 ]

Yield	Reaction Conditions	Operation in experiment
79%	With sodium hydride; In tetrahydrofuran; at 0 - 20℃; for 1h;	To a solution of 6-bromo-1 H-indazole (2.00 g, 10.2 mmol) in THF (30 mL) was added NaH (0.820 g, 20.4 mmol) at 0 C. The mixture was stirred at rt for 30 mm. SEM-CI (2.55 g, 15.3 mmol) was added to the mixture at 0 C. The mixture was stirred at room temperature for another 1 h. The mixture was diluted with H20 (50 mL) and extracted with EtOAc (3 x 20 mL). The combined organic layers were washed with brine, dried over Na2SO4 andconcentrated under vacuum. The residue was purified by silica columm (PE: EtOAc = 60: 1)to give the desired product (2.62 g, yield 79%) as a red oil.1H NMR (300 MHz, CDCI3): 6 7.97 (s, 1H), 7.77 (s, 1H), 7.60 (d, J 8.7 Hz, 1H), 7.30 (dd, J= 8.7, 1.5 Hz, 1 H), 5.69 (s, 2H), 3.53 (t, J = 8.1 Hz, 2H), 0.89 (t, J = 8.1 Hz, 2H), -0.06 (s,9H).LC-MS: [mobile phase: from 90% water (0.02% NH4OAc) and 10% CH3CN to 5% water (0.02% NH4OAc) and 95% CH3CN in 4 mm], Rt = 2.981 mm MS Calcd.: 326, MS Found: 327 [M+H].

Reference： [1]Patent: WO2017/12576,2017,A1 .Location in patent: Page/Page column 205

48
[ 79762-54-2 ]
[ 744219-43-0 ]

Reference： [1]Patent: WO2017/12576,2017,A1

49
[ 79762-54-2 ]
[ 1209458-23-0 ]
6-bromo-1-(6-ethylpyrazin-2-yl)-1H-indazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	With sodium hydride; In water-d2; at 120℃; for 2h;Inert atmosphere;	A mixture of 2-chloro-6-ethylpyrazine (520 mg, 3.7 mmol, 1.0 eq), 6-bromo- lH-indazole (0493) (798 mg, 4.1 mmol, 1.1 eq) and NaH (164 mg, 4.1 mmol, 1.1 eq) in DMF (10 mL) was stirred while purging N2 at 120 C for 2 h. The mixture was diluted with EA (100 mL) and washed with H20 (50 mL x 3). The organic phase was dried over Na2S04. After filtration and concentration, the residue was purified by silica gel chromatography (PE/EA = 10/1) to give 6-bromo- l-(6- ethylpyrazin-2-yl)- lH-indazole (620 mg, Y: 56%) as a yellow solid. ESI-MS (M+H)+: 303.1. 1H NMR (400 MHz, CDC13) S: 9.20 (s, 1H), 9.03 (s, 1H), 8.34 (s, 1H), 8.20 (s, 1H), 7.65 (d, J = 8.4 Hz, 1H), 7.43 (d, / = 8.4 Hz, 1H), 2.97 (q, J = 7.6 Hz, 2H), 1.48 (t, J = 7.6 Hz, 3H).

Reference： [1]Patent: WO2017/127430,2017,A1 .Location in patent: Page/Page column 59

50
[ 79762-54-2 ]
[ 39890-95-4 ]
6-bromo-1-(6-(trifluoromethyl)pyridin-2-yl)-1H-indazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
34%	With sodium hydride; In N,N-dimethyl-formamide; at 150℃; for 3h;	To a solution of 6-bromo-1H-indazole (Cas No. 79762-54-2, 400 mg, 2.04 mmol, 1.0 eq) in DMF (6 mL) was added NaH (90 mg, 2.24 mmol, 1.1 eq) at 0C. After stirring at 0C for 15 mm, Methyl 2-chloropyrimidine-4-carboxylate (CAS No. 149849-94-5, 352 mg, 2.04 mmol, 1.0eq) dissolved in DMF (2 mL) was added and the reaction mixture was stirred at 0 C for 1 h. The reaction mixture was poured into H20 (40 mL) and stirred at ft for 15 mm. The precipitate was collected by filtration and dried to give methyl 2-(6-bromo-1H-indazol-1-yl)pyrimidine-4- carboxylate.;_The preparation of 6-bromo- 1 -(6-(trifluoromethyl)pyridin-2-yl)- 1 H-indazole was similar to that of methyl 2-(6-bromo- 1 H-indazol- 1 -yl)pyrimidine-4-carboxylate (Example 8, Step 1). 600 mg, as a yellow solid, Y: 34 %. ESI-MS (M+H): 342.0.

Reference： [1]Patent: WO2017/127430,2017,A1 .Location in patent: Page/Page column 42; 43; 48

51
[ 79762-54-2 ]
[ 33034-67-2 ]
6-bromo-1-(4-(trifluoromethyl)pyrimidin-2-yl)-1H-indazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	With sodium hydride; In N,N-dimethyl-d6-formamide; at 110℃; for 3h;	To a solution of <strong>[79762-54-2]6-bromo-1H-indazole</strong> (2.5 g, 12.7 mmol, 1.0 eq) in dry DMF (10 mL) was slowly added NaH (560 mg, 14.0 mmol, 1.1 eq) at rt. After stirring at ft for 10 mm, 2-chloro-4-ethylpyrimidine (2.0 g, 14.0 mmol, 1.1 eq) was added to the mixture. Then the mixturewas stirred at 130 C for 4 h under N2 atmosphere. After cooling down to rt, the mixture wasdiluted with H20 (50 mL) and stirred at ft for 10 mm. The precipitate was collected by filtration and was purified by silica gel chromatography (PE/EA = 3/1) to give 6-bromo-1-(4-ethylpyrimidin-2-yl)-1H-indazole as a yellow solid. 3.5 g,;_The preparation of 6-bromo- 1 -(4-(trifluoromethyl)pyrimidin-2-yl)- 1 H-indazole was similar to that of 6-bromo-1-(4-ethylpyrimidin-2-yl)-1H-indazole (Example 11, Step 1) to give 400mg as a yellow solid. Y: 58%. ESI-MS (M+H): 343.1. ?H NMR (400 MHz, CDC13) (5: 9.10 (d, J= 4.8 Hz, 1H), 8.97 (s, 1H), 8.33 (s, 1H), 7.68 (d, J= 8.4 Hz, 1H), 7.59-7.41 (m, 2H).

Reference： [1]Patent: WO2017/127430,2017,A1 .Location in patent: Page/Page column 50; 55

52
[ 79762-54-2 ]
[ 149849-94-5 ]
(2-(6-bromo-1H-indazol-1-yl)pyrimidin-4-yl)methanol [ No CAS ]

Reference： [1]Patent: WO2017/127430,2017,A1

53
[ 79762-54-2 ]
[ 188707-99-5 ]
6-bromo-1-(4-ethylpyrimidin-2-yl)-1H-indazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%		To a solution of <strong>[79762-54-2]6-bromo-1H-indazole</strong> (2.5 g, 12.7 mmol, 1.0 eq) in dry DMF (10 mL) was slowly added NaH (560 mg, 14.0 mmol, 1.1 eq) at rt. After stirring at ft for 10 mm, 2-chloro-4-ethylpyrimidine (2.0 g, 14.0 mmol, 1.1 eq) was added to the mixture. Then the mixturewas stirred at 130 C for 4 h under N2 atmosphere. After cooling down to rt, the mixture wasdiluted with H20 (50 mL) and stirred at ft for 10 mm. The precipitate was collected by filtration and was purified by silica gel chromatography (PE/EA = 3/1) to give 6-bromo-1-(4-ethylpyrimidin-2-yl)-1H-indazole as a yellow solid. 3.5 g, Y: 91%. ESI-MS (M+H): 303.1. ?H NMR (400 MHz, CDC13) (5: 9.06 (s, 1H), 8.69 (d, J = 5.2 Hz, 1H), 8.26 (s, 1H), 7.64 (d, J = 8.4Hz, 1H), 7.42 (d, J= 8.0 Hz, 1H), 7.07 (d, J= 5.2 Hz, 1H), 2.96 (q, J= 7.6 Hz, 2H), 1.43 (t, J= 7.6 Hz, 3H).

Reference： [1]Patent: WO2017/127430,2017,A1 .Location in patent: Page/Page column 50

54
[ 79762-54-2 ]
[ 162607-15-0 ]
6-(4-methylthiophen-2-yl)-1H-indazole [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2017,vol. 8,p. 1264 - 1268

55
[ 79762-54-2 ]
[ 872041-85-5 ]
6-(5-chloropyridin-3-yl)-1H-indazole [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2017,vol. 8,p. 1264 - 1268

56
[ 79762-54-2 ]
[ 319460-85-0 ]

Reference： [1]Beilstein Journal of Organic Chemistry,2018,vol. 14,p. 786 - 795

57
[ 79762-54-2 ]
[ 79-06-1 ]
(E)-3-(1H-indazol-6-yl)acrylamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	With palladium diacetate; N-ethyl-N,N-diisopropylamine; tris-(o-tolyl)phosphine; In 1-methyl-pyrrolidin-2-one; at 130℃; for 18h;Inert atmosphere;	A stirred mixture of N,N-diisopropylethylamine (0.532 mL, 3.05 mmol) and <strong>[79762-54-2]6-bromo-1H-indazole</strong> (500 mg, 2.54 mmol) and acrylamide (180 mg, 2.54 mmol) and tri(o-toly)lphosphine (77 mg, 0.25 mmol) in dry N-methylpyrrolidinone (5 mL) was degassed with nitrogen for 10 minutes and then treated with palladium(II) acetate (28.5 mg, 0.13 mmol). The reaction mixture was stirred under nitrogen for 18 hours at 130 C. The mixture was partitioned between 2-methyltetrahydrofuran and aqueous brine, the aqueous layer was extracted with further 2-methyltetrahydrofuran (x5) and the combined organics were, dried, filtered and the solvent removed under reduced pressure. The crude product was purified by flash silica chromatography, elution gradient 0 to 5% methanol in ethyl acetate. Pure fractions were evaporated to dryness and the residue tritrurated with ethanol (5 mL) to afford (E)-3-(1H-indazol-6-yl)acrylamide (290 mg, 61%) as a white solid. 1H NMR (400 MHz, DMSO, 30 C): delta (ppm) 6.68 (d, J=15.8 Hz, 1H), 7.09 (s, 1H), 7.34 (d, J=8.4 Hz, 1H), 7.49 - 7.60 (m, 2H), 7.67 (s, 1H), 7.77 (d, J=8.4 Hz, 1H), 8.07 (s, 1H), 13.18 (s, 1H). 13C NMR (126 MHz, DMSO, 30 C) 110.4, 119.0, 121.1, 122.5, 123.4, 132.9, 133.7, 139.9, 140.3, 166.8. ESI+ obs 188.08176 calc 188.08184. HPLC Purity 98.7%.

Reference： [1]Tetrahedron Letters,2018,vol. 59,p. 2917 - 2920

58
[ 79762-54-2 ]
[ 98-89-5 ]
C₁₃H₁₅BrN₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With copper(I) thiophene-2-carboxylate; (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(5-methyl-2-(4-fluorophenyl)pyridine(-1H))-iridium(III) hexafluorophosphate; N,N,N?,N?-tetramethyl-N?-tert-butylguanidine; bathophenanthroline; iodomesitylene diacetate; In 1,4-dioxane; at 20℃; for 1h;Inert atmosphere; Irradiation;	General procedure: To a 20 ml or 40 ml viale quipped with a stir bar was added photocatalyst, nitrogen nucleophile, iodomesitylene dicarboxylate, copper salt, and ligand. Dioxane was added followed by addition of the base. The solution was sonicated for 1-3 min until it became homogeneous. Next, the solution was degassed by sparging with nitrogen for 5-10 min before sealing with Parafilm. The reaction was stirred and irradiated using two 34-W blue LED lamps (3 cm away, with cooling fan to keep the reaction at room temperature) for 1 h. The reaction mixture was removed from the light, cooled to ambient temperature, diluted with water (15 ml) and ethyl acetate (25 ml), and the aqueous layer was extracted with ethyl acetate (3 × 25 ml). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography on silica gel to afford the desired decarboxylative C-N coupling product. For aniline substrates, a solution of these nitrogen nucleophiles in dioxane was used; additionally, if the iodomesitylene dicarboxylate is a liquid, its solution in dioxane was used.

Reference： [1]Nature,2018,vol. 559,p. 83 - 88

59
[ 79762-54-2 ]
[ 39267-79-3 ]
6-bromo-1-(oxetan-3-yl)indazole [ No CAS ]
6-bromo-2-(oxetan-3-yl)indazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.6 g; 0.6 g	With potassium carbonate; In N,N-dimethyl-formamide; at 85℃; for 16h;	Step-1: A solution of6-bromo-lH-indazole (2 g, 10.2 mmol), <strong>[39267-79-3]3-bromooxetane</strong> (2.7 g, 20.4 mmol) and anhydrous K2CO3 (2.8 g, 20.4 mmol) in DMF (15 mL) was stirred at 85 C for 16 h. It was then cooled to room temperature and diluted using water (50 mL). Extraction was carried out using EtOAc (30 mL x 3); the combined organic layers were washed with water (50 mL x 2); brine (50 mL); dried over anhydrous Na2S04, filtered and concentrated under reduced pressure. The residue obtained was purified using silica gel column chromatography (0-30% EtOAc in hexane) to provide desired intermediates III-B-4 (non-polar spot) (0.6 g) and III-B- 5 (polar spot) (0.6 g). III-B-4:LCMS: m/z; 253 (M+1)+. 1H NMR (CDCI3; 400 MHz) 5.11-5.15 (m, 2H); 5.25-5.29 (m, 2H); 5.69-5.76 (m, 1H); 7.26-7.30 (aromatics, 1H); 7.61 (d, J = 8.8 Hz, 1H); 7.71 (s, 1H); 8.06 (s, 1H). III-B-5:LCMS: m/z; 253 (M+1)+. 1H NMR (CDCI3; 400 MHz) 5.14-5.21 (m, 4H); 5.66-5.73 (m, 1H); 7.19 (dd, Jl= 1.5 Hz, J2 = 8.9 Hz, 1H); 7.54 (d, J = 8.8 Hz, 1H); 7.93 (s, 1H); 8.09 (s, 1H).

Reference： [1]Patent: WO2018/167800,2018,A1 .Location in patent: Paragraph 00013

60
[ 79762-54-2 ]
[ 493-05-0 ]
C₁₆H₁₃BrN₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With [bis(acetoxy)iodo]benzene; In 1,2-dichloro-ethane; at 20 - 80℃; for 6h;Schlenk technique;	General procedure: PhI(OAc)2 (0.5 mmol) was added to a mixture of 1H-benzimidazole(1a; 0.5 mmol), isochroman (2a; 2.0 mmol), and DCE (2.0mL) in a Schlenk tube at r.t. The mixture was stirred at 80 C for6 h then cooled. H2O (10 mL) was added, and the mixture wasextracted with CH2Cl2 (3 × 10 mL). The combined organic layerwas dried (Na2SO4) and concentrated under reduced pressure.The residues were purified by flash column chromatography(silica gel, hexane-EtOAc) to give a colorless oil; yield: 115 mg(92%).

Reference： [1]Synlett,2018,vol. 29,p. 2432 - 2436

61
[ 79762-54-2 ]
[ 5722-11-2 ]
1-(1H-indazol-6-yl)-2,2-dimethylcyclopropane-1-carbonitrile [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2019,vol. 84,p. 4670 - 4679

62
[ 79762-54-2 ]
[ 4426-11-3 ]
1-(1H-indazol-6-yl)cyclobutane-1-carbonitrile [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2019,vol. 84,p. 4670 - 4679

63
[ 79762-54-2 ]
[ 4254-02-8 ]
1-(1H-indazol-6-yl)cyclopentane-1-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	With N-Xantphos Pd G₄; lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 3h; Inert atmosphere; Sealed tube;

Reference： [1]Wright, Brandon A.; Ardolino, Michael J. [Journal of Organic Chemistry, 2019, vol. 84, # 8, p. 4670 - 4679]

64
[ 79762-54-2 ]
[ 52462-29-0 ]
[ 94957-44-5 ]
[ 38385-95-4 ]
C₃₉H₄₁Cl₂N₅O₃RuS⁽¹⁺⁾*Cl^(1-) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		S2, weigh 200 mg of 2-(4-piperidinyl) benzimidazole,Then add 19 mL of carbon tetrachloride solvent in sequence.0.8 mg of azobisisobutyronitrile, 170 mg of N-bromosuccinimide,Reflow at 60 C for 20 h,After removing the solvent by rotary evaporation, 118 mg of 6-bromocarbazole was added.31 mg of intermediate product, co-dissolved in 14 mL of anhydrous toluene,Add 0.18 mg of NaOH again under stirring.0.08 mL of ethylenediamine, 2.8 mg of cesium carbonate,5.5 mL of triethylamine, then pass nitrogen for 30 min,Then add 14.5 mg of tetrakis(triphenylphosphine)palladium,1.8 mg of CuI, 49 mg of propynyl p-toluenesulfonate,Reacted at 75 C for 22 h,Finally, 0.8 mg of zinc chloride and 0.8 mL of 10% by mass of hydrochloric acid were added.Precipitating a red solid,It is a phototoxic anti-tumor compound.

Reference： [1]Patent: CN108752390,2018,A .Location in patent: Sheet 0033; 0037; 0047

65
[ 79762-54-2 ]
3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(3-(trifluoromethyl)phenyl)benzamide [ No CAS ]
3-(1H-indazol-6-yl)-N-(3-(trifluoromethyl)phenyl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%		To a resealable vial was added 77 K2CO3 (112mg, 0.81mmol), 105 17 (175mg, 0.45mmol), 98 <strong>[79762-54-2]6-bromo-1H-indazole</strong> (80.0mg, 0.41mmol). The vial was sealed and evacuated and purged with Ar for 5min before addition of PdCl2(dppf)-CH2Cl2 Adduct (20mg, 0.02mmol), dissolved in 79 1,4-dioxane/80 water (10mL, 4:1, v/v) was then added to this solution before the vial was heated to 80C overnight. The reaction was cooled to room temperature, which was then brought to basic using 81 aqueous sodium bicarbonate solution and extracted with ethyl acetate. The organic layer was collected and distilled under reduced pressure. The crude residue was purified via by silica gel column chromatography (eluting with 0-30% EtOAc in 82 petroleum ether) to afford the 107 product as a white solid (96mg, 62%). 1H NMR (400MHz, Methanol-d4) delta 8.31 (s, 1H), 8.22 (s, 1H), 8.10 (s, 1H), 8.02-7.94 (m, 3H), 7.90 (d, J=8.4Hz, 1H), 7.86 (s, 1H), 7.66 (t, J=7.8Hz, 1H), 7.59 (d, J=7.9Hz, 1H), 7.58-7.52 (m, 1H), 7.46 (d, J=7.8Hz, 1H). 13C NMR (126MHz, DMSO-d6) delta 166.31, 141.31, 140.98, 140.43, 137.95, 135.58, 133.94, 131.04, 130.36, 129.98, 129.72, 127.35, 126.80, 124.64 (d, J=272.2Hz), 124.30, 122.91, 121.61, 120.60, 120.48, 116.92, 108.51.HRMS m/z (ESI) found 382.1168 (M+H)+, C21H15F3N3O+ calcd for 382.1162, retention time 3.76min, >97% pure.