[ CAS No. 40598-94-5 ] {[proInfo.proName]}

Name: 40598-94-5|3-Bromo-1H-indazole|97%
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SKU: A153191
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Quality Control of [ 40598-94-5 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 40598-94-5 ]

CAS No. :	40598-94-5	MDL No. :	MFCD00159926
Formula :	C₇H₅BrN₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	HTKXRTUKPXEALT-UHFFFAOYSA-N
M.W :	197.03	Pubchem ID :	721568
Synonyms :

Calculated chemistry of [ 40598-94-5 ]

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) :	-5.67 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.33
Log Po/w (XLOGP3) :	2.58
Log Po/w (WLOGP) :	2.33
Log Po/w (MLOGP) :	2.15
Log Po/w (SILICOS-IT) :	2.75
Consensus Log Po/w :	2.23

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.35
Solubility :	0.0874 mg/ml ; 0.000444 mol/l
Class :	Soluble
Log S (Ali) :	-2.83
Solubility :	0.291 mg/ml ; 0.00148 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 :	1.73

Safety of [ 40598-94-5 ]

Signal Word:	Danger	Class:	6.1
Precautionary Statements:	P261-P301+P310-P305+P351+P338	UN#:	2811
Hazard Statements:	H301-H315-H319-H335	Packing Group:	Ⅲ
GHS Pictogram:

Application In Synthesis of [ 40598-94-5 ]

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

Upstream synthesis route of [ 40598-94-5 ]
Downstream synthetic route of [ 40598-94-5 ]

[ 40598-94-5 ] Synthesis Path-Upstream 1~11

1
[ 271-44-3 ]
[ 40598-94-5 ]

Yield	Reaction Conditions	Operation in experiment
80%	With hydrogenchloride; bromine; sodium hydrogensulfite In sodium hydroxide	A. 3-Bromo-1H-indazole To a suspension of 1H-indazole (3.00 g, 25.4 mmol) in 2.0 M sodium hydroxide solution (70 mL) at ambient temperature was added a solution of bromine (3.00 g, 18.8 mmol) in 2.0 M sodium hydroxide solution (30 mL) dropwise. After stirring for 3 hours, to the reaction mixture was added sodium bisulfite (0.1 g), followed by 2.0 N hydrochloric acid solution (80 mL). The precipitates were filtered and washed with water to provide the title compound (3.98 g, 80percent yield): mp 136° C.; ¹H NMR (CDCl₃) δ 13.4 (br s, 1H), 7.57 (m, 2H), 7.45 (t, 1H), 7.22 (t, 1H); EI-MS (m/z) 198 [M+2]⁺, 196 [M]⁺.
80%	at 20℃; for 3 h;	Bromine (1.5g, 9.4mmol) in 2M NaOH solution (lOmL) was added drop wise tosuspension of indazole (1.5g, 12.7mmol) in 2M NaOH solution (23mL) at ambient temperature. Stined the reaction mass for 3h at room temperature and added sodium bisulfate (0.05g) followed by the addition of 2N HC1. The solid precipitated was filtered out and washed with water, suction dried followed by in Rotavap under reduced pressure to afford the title compound (2g, 80percent). LCMS: mlz = 197.1 (M+H).
45%	With bromine; sodium hydrogensulfite In sodium hydroxide	3-Bromoindazole 4a was prepared using a procedure described by Boulton, B. E. and Coller, A. W (Aust. J Chem., 1974, 27, 2343-2346): A solution of bromine (0.99 g, 6.19 mmol) in 10percent NaOH was slowly added to a suspension of indazole (1 g, 8.50 mmol) in 2 N NaOH (25 mL). The reaction mixture became a thick white slurry. After stirring for 2 hours, a small amount of sodium bisulfite was added and the solution was neutralized with 1 N HCl. The white solid was filtered and washed with water. Recrystallization from water gave 0.76 g (45percent yield) of 3-bromoindazole 4a: ¹H NMR (CDCl₃) δ 7.22-7.27 (m, 1H), 7.43-7.52 (m, 2H), 7.60-7.67 (m, 1H); IR (KBr, cm^-1) 3154, 2944, 2915, 1624, 1479, 1331, 1242, 1026, 901, 770, 735, 639; MS m/e 195 (MH^-); Anal. Calcd for C₇H₅BrN₂: C, 42.67; H, 2.56; N, 14.22 Found: C, 42.37; H, 2.55; N, 14.06.

Reference： [1] RSC Advances, 2016, vol. 6, # 93, p. 90031 - 90034
[2] Journal of Organic Chemistry, 2018, vol. 83, # 2, p. 930 - 938
[3] Organic Letters, 2015, vol. 17, # 4, p. 1042 - 1045
[4] Patent: US2002/103229, 2002, A1,
[5] Patent: US2004/127536, 2004, A1,
[6] Patent: US2005/9876, 2005, A1,
[7] Patent: WO2016/193939, 2016, A1, . Location in patent: Page/Page column 84
[8] Synthesis, 2011, # 16, p. 2651 - 2663
[9] Patent: US2002/99208, 2002, A1,
[10] Journal fuer Praktische Chemie (Leipzig), 1924, vol. <2> 108, p. 314
[11] Patent: WO2006/50006, 2006, A2, . Location in patent: Page/Page column 47-48

2
[ 2596-89-6 ]
[ 40598-94-5 ]

Reference： [1] Chemische Berichte, 1899, vol. 32, p. 1799[2] Justus Liebigs Annalen der Chemie, 1899, vol. 305, p. 354 Anm. 10

3
[ 2596-89-6 ]
[ 10035-10-6 ]
[ 271-44-3 ]
[ 53857-57-1 ]
[ 40598-94-5 ]
[ 40598-76-3 ]

Reference： [1] Chemische Berichte, 1899, vol. 32, p. 1781

4
[ 40598-94-5 ]
[ 66607-27-0 ]

Reference： [1] Patent: US2002/99208, 2002, A1,

5
[ 40598-94-5 ]
[ 75-36-5 ]
[ 4498-72-0 ]

Reference： [1] Synthesis, 1992, # 10, p. 937 - 939

6
[ 40598-94-5 ]
[ 40598-76-3 ]

Reference： [1] Chemische Berichte, 1922, vol. 55, p. 1141,1157

7
[ 7726-95-6 ]
[ 40598-94-5 ]
[ 64-19-7 ]
[ 40598-76-3 ]

Reference： [1] Chemische Berichte, 1922, vol. 55, p. 1141,1157

8
[ 2596-89-6 ]
[ 10035-10-6 ]
[ 271-44-3 ]
[ 53857-57-1 ]
[ 40598-94-5 ]
[ 40598-76-3 ]

Reference： [1] Chemische Berichte, 1899, vol. 32, p. 1781

9
[ 40598-94-5 ]
[ 465529-56-0 ]

Reference： [1] Chemische Berichte, 1922, vol. 55, p. 1141,1157

10
[ 40598-94-5 ]
[ 465529-57-1 ]

Reference： [1] Chemische Berichte, 1922, vol. 55, p. 1141,1157
[2] Chemische Berichte, 1922, vol. 55, p. 1141,1157

11
[ 40598-94-5 ]
[ 130641-38-2 ]

Reference： [1] Patent: WO2011/15501, 2011, A1,
[2] Patent: WO2011/15502, 2011, A1,

[ 40598-94-5 ] Synthesis Path-Downstream 1~88

1
[ 2596-89-6 ]
[ 40598-94-5 ]

Reference： [1]Chemische Berichte,1899,vol. 32,p. 1799
Justus Liebigs Annalen der Chemie,1899,vol. 305,p. 354 Anm. 10

2
[ 40598-94-5 ]
[ 108-94-1 ]
[ 144730-61-0 ]

Reference： [1]Synthesis,1992,p. 937 - 939

3
[ 40598-94-5 ]
[ 100-52-7 ]
[ 33100-54-8 ]

Reference： [1]Synthesis,1992,p. 937 - 939

4
[ 40598-94-5 ]
[ 98-88-4 ]
[ 59591-73-0 ]

Reference： [1]Synthesis,1992,p. 937 - 939

5
[ 40598-94-5 ]
[ 100-47-0 ]
[ 144730-63-2 ]

Reference： [1]Synthesis,1992,p. 937 - 939

6
[ 40598-94-5 ]
[ 75-36-5 ]
[ 4498-72-0 ]

Reference： [1]Synthesis,1992,p. 937 - 939

7
[ 40598-94-5 ]
[ 98-86-2 ]
[ 144730-62-1 ]

Reference： [1]Synthesis,1992,p. 937 - 939

8
[ 40598-94-5 ]
[ 67-64-1 ]
[ 58706-33-5 ]

Reference： [1]Synthesis,1992,p. 937 - 939
[2]Synthesis,1992,p. 937 - 939

9
[ 40598-94-5 ]
[ 83553-84-8 ]
3-bromo-1-nitroindazole [ No CAS ]
3-bromo-1,4-dinitroindazole [ No CAS ]

Reference： [1]Organic Magnetic Resonance,1982,vol. 19,p. 225 - 227

10
[ 40598-94-5 ]
1-benzylidenamino-3-bromoindazole [ No CAS ]

Reference： [1]Chemistry of Heterocyclic Compounds,1994,vol. 30,p. 1174 - 1181
Khimiya Geterotsiklicheskikh Soedinenii,1994,p. 1355 - 1363

11
[ 40598-94-5 ]
4-(3-bromoindazolyl-1)aminobenzo-1,2,3-triazine [ No CAS ]

Reference： [1]Chemistry of Heterocyclic Compounds,1994,vol. 30,p. 1174 - 1181
Khimiya Geterotsiklicheskikh Soedinenii,1994,p. 1355 - 1363

12
[ 40598-94-5 ]
[ 52088-11-6 ]

Reference： [1]Chemische Berichte,1922,vol. 55,p. 1141,1157
[2]Journal fur praktische Chemie (Leipzig 1954),1924,vol. <2> 108,p. 314
[3]Chemische Berichte,1922,vol. 55,p. 1141,1157
[4]Journal fur praktische Chemie (Leipzig 1954),1924,vol. <2> 108,p. 314

13
[ 40598-94-5 ]
2-acetyl-5-bromo-2H-indazole [ No CAS ]

Reference： [1]Chemische Berichte,1922,vol. 55,p. 1141,1157

14
[ 40598-94-5 ]
1-acetyl-3,5-dibromo-1H-indazole [ No CAS ]

Reference： [1]Chemische Berichte,1922,vol. 55,p. 1141,1157
[2]Chemische Berichte,1922,vol. 55,p. 1141,1157

15
[ 40598-94-5 ]
[ 53857-57-1 ]

Reference： [1]Chemische Berichte,1922,vol. 55,p. 1141,1157

16
[ 5720-07-0 ]
[ 40598-94-5 ]
[ 55271-06-2 ]

Yield	Reaction Conditions	Operation in experiment
5%	With sodium carbonate;tetrakis(triphenylphosphine)palladium (0); In 1,2-dimethoxyethane;	B. 3-(4-Methoxyphenyl)-1H-indazole A mixture of <strong>[40598-94-5]3-bromo-1H-indazole</strong> (0.20 g, 1.0 mmol), 4-methoxyphenylboronic acid (0.228 g, 1.5 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.228 g, 0.1 mmol) in ethylene glycol dimethyl ether (5 mL) and 2.0 M sodium carbonate solution (6 mL) under nitrogen was heated at 100 C. for 18 hours. It was quenched by water and extracted with chloroform. The extracts were dried over magnesium sulfate, filtered, and concentrated. The residue was then purified by chromatography (SiO2, 15-30% ethyl acetate/hexane) to provide the title compound (0.012 g, 5% yield): 1H NMR (CDCl3) delta 10.4 (br s, 1H), 8.01 (d, 1H), 7.92 (d, 2H), 7.46 (m, 2H), 7.22 (m, 1H), 7.06 (d, 2H), 3.89 (s, 3H); EI-MS (m/z) 224 [M]+.

Reference： [1]Patent: US2002/103229,2002,A1

17
[ 40598-94-5 ]
[ 66607-27-0 ]

Yield	Reaction Conditions	Operation in experiment
89%		3-iodoindazole (5a) was prepared using the same procedure as compound 4a with iodine in 89% yield: 1H NMR (CDCl3) delta 7.21-7.27 (m, 1H), 7.43-7.60 (m, 3H); IR (KBr, cm-1) 3153, 2933, 2903, 1620, 1472, 1344, 1321, 1239, 1013, 899, 769, 747, 738; MS m/e 243 (MH-); Anal. Calcd for C7H5IN2: C, 34.45; H, 2.07; N, 11.45 Found: C, 34.62; H, 1.97; N, 11.38.

Reference： [1]Patent: US2002/99208,2002,A1

18
3-benzyloxyoxybenzaldehyde [ No CAS ]
[ 40598-94-5 ]
[ 885694-02-0 ]

Yield	Reaction Conditions	Operation in experiment
	With n-butyllithium; tert.-butyl lithium; In diethyl ether; hexane; pentane; at -78℃; for 0.25h;	Example 1 ; 3-[(l//-indazol-3-yl)methyl]phenol; Step A: [3-(benzyloxy)phenyl](lJ-indazol-3-yl)methanol[0171] ; A solution of <strong>[40598-94-5]3-bromoindazole</strong> (3.2 g, 16.4 mmol) in 50 mL Et2O was cooled to -78C and treated dropwise with n-butyllithium (6.6 mL, 16.4 mmol, 2.5M in hexanes). After the addition was complete, t-butyllithiurn (19 mL, 32.4 mmol, 1.7M in pentane) was added dropwise to the cooled solution. The mixture was stirred at - 78C for 15 minutes after which 3-benzyloxyoxybenzaldehyde (3.8 g, 18 mmol) was added in one portion. The cooling bath was removed and the solution was allowed to warm to ambient temperature. The reaction was quenched with IN HCl and extracted with EtOAc. The organic phase was washed with brine and dried (Na2SO4). Removal of the solvent afforded the crude product which was purified by flash chromatography (silica gel, hexane-ethyl acetate, 3:2) to give the title compound, 1.3 g off-white solid, mp 124-125 C;1H NMR (DMSO-d6): delta 5.05 (s, 2H), 6.03 (s, 2H), 6.83 (dd, IH), 6.97 (m, 2H), 7.13 (s, IH), 7.18 (t, IH), 7.24-7.32 (m, 2H), 7.35 (t, IH), 7.42 (m, 4H), 7.64 (d, IH), 12.74 (s, IH).MS (ESI) m/z 329 ([M-H]"); Anal, calcd for C21H18N2O2: C:76.34 H:5.49 N:8.48 Found: C:75.90 H:5.47 N:8.41.

Reference： [1]Patent: WO2006/50006,2006,A2 .Location in patent: Page/Page column 49

19
[ 917494-85-0 ]
[ 40598-94-5 ]
[ 1032648-16-0 ]

Yield	Reaction Conditions	Operation in experiment
19%		Example 3: 2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(lH-indazol-3- yl)ethanol; To a chilled (-780C) solution of 97 mg (0.49 mmol) of 3-bromo-lH-indazole in 5 niL of anhydrous ether was added 195 muL (0.49 mmol) of a 2.5 M solution of n-BuLi in hexanes dropwise. After 5 minutes, 590 muL (1.0 mmol) of a 1.7 M solution of tert-BuLi in pentane was added dropwise. The mixture stirred for 15 minutes and then a solution of 151 mg (0.49 mmol) of 2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanone in 3 mL of ether was added dropwise. After 1 hour, the reaction was monitored by thin layer chromatography (30% ethyl acetate-hexanes) and LCMS. The mixture was diluted with 10 mL of saturated aqueous ammonium chloride and extracted with three 10 mL portions of ethyl acetate. The combined organic layers were washed with three 10 mL portions of brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude residue was chromatographed on silica gel using dichloromethane-hexanes (1 : 1) to load the sample and then eluting with dichloromethane- hexanes (1 : 1, then 100:0) followed by ethyl acetate-hexanes (2:8). The material from the column was triturated with ether-hexanes to afford 41 mg (19%) of the title compound. MS m/z 427.20 (MH+).

Reference： [1]Patent: WO2008/70507,2008,A2 .Location in patent: Page/Page column 114-115

20
[ 40598-94-5 ]
[ 407-25-0 ]
[ 1040502-31-5 ]

Yield	Reaction Conditions	Operation in experiment
		a) To a solution of 3-bromo-1 H-indazole (400mg) (preparation according to Zhurnal Obshchei Khimii 1964, 34(8), 2777) in dry diethyl ether (1 OmL) cooled to -78C is added a solution of n- butyl lithium (n-BuLi, 0.81 ml_, 2.5M in hexanes). After 5 min. a solution of t-BuLi (2.39ml_, 1.7M in pentane) is added dropwise while keeping the temperature below -70C. The reaction mixture is stirred for 15min. at -78C and a solution of trifluoroacetic acid anhydride (0.34ml_) in diethyl ether (1 ml.) is added. The reaction mixture is stirred for 1 h at -78C and then allowed to warm slowly to room temperature. A saturated solution of ammonium chloride in H2O is added and the mixture is extracted with diethyl ether. The combined organic phases are washed with water and brine, dried over MgSO4 and filtered. After removal of the solvent the residue is purified by preparative reverse-phase chromatography on a Daisogel C18-ODS AP column with a water/formic acid (10'000:1 ) to acetonitrile/formic acid (10'000:1 ) to give 2,2,2-trifluoro-1-(1 H- indazol-3-yl)-ethanone after removal of the solvents.

Reference： [1]Patent: WO2008/74757,2008,A1 .Location in patent: Page/Page column 22

21
[ 421-50-1 ]
[ 40598-94-5 ]
[ 1040502-35-9 ]

Yield	Reaction Conditions	Operation in experiment
		a) To a solution of 3-bromo-1 H-indazole (331 mg) (preparation according to Zhurnal Obshchei Khimii 1964, 34(8), 2777) in dry diethyl ether (9mL) cooled to -78C is added a solution of n-BuLi (0.67mL, 2.5M in hexanes). After 5 min. a solution of t-BuLi (1.98mL, 1.7M in pentane) is added dropwise while keeping the temperature below -700C. The reaction mixture is stirred for 15min. at -78C and 1 ,1 ,1-trifluoroacetone (0.18mL) is added. The reaction mixture is stirred for 1 h at - 78C and then allowed to warm slowly to room temperature. A saturated solution of ammonium chloride in H2O is added and the mixture is extracted with diethyl ether. The combined organic phases are washed with water and brine, dried over MgSO4 and filtered. After removal of the solvent the residue is purified by preparative reverse-phase chromatography on a Daisogel C18- <n="24"/>ODS AP column with a water/formic acid (10'000:1 ) to acetonitrile/formic acid (10'000:1 ) to give 1 ,1 ,1-trifluoro-2-(1 /-/-indazol-3-yl)-propan-2-ol after removal of the solvents,

Reference： [1]Patent: WO2008/74757,2008,A1 .Location in patent: Page/Page column 22-23

22
[ 110-87-2 ]
[ 40598-94-5 ]
[ 60869-95-6 ]

Yield	Reaction Conditions	Operation in experiment
98%	With toluene-4-sulfonic acid; In ethyl acetate; for 48h;Reflux;	3,4-Dihydro-2H-pyran (0.232 mL, 2.54 mmol) and p-toluenesulfonic acid monohydrate (0.024 g, 0.127 mmol) were added to a solution of <strong>[40598-94-5]3-bromo-1H-indazole</strong> (0.250 g, 1.269 mmol) in ethyl acetate (12.0 ml), and the mixture was heated at reflux for 48 h. The reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution. The aqueous phase was separated and extracted with ethyl acetate. The combined organic phases were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated to afford an orange oil. This material was purified via column chromatography on silica gel (Biotage 25 g column. gradient elution with 0-25% ethyl acetate-hexane) to afford 3-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (0.350 g, 98%) as a colorless oil. MS (ESI, pos. ion) m/z 281, 283 [M+H]+.
72%	With toluene-4-sulfonic acid; In ethyl acetate; at 95℃;	General procedure: A solution of the correspond indazole (1.0 equiv.), DHP (2.0equiv.) and PTSA (5 mol%) in EtOAc (0.7 mmol/mL) was heatedovernight at 95 C. After cooling, the solution was concentratedunder vacuum. The residuewas diluted withwater and the aqueousphase was extracted 3 times with EtOAc. The combined organiclayers were washed with water and brine, dried over Na2SO4,filtered, concentrated and purified by silica gel column chromatography,using the appropriate heptanes:EtOAc mixture.
51%	With toluene-4-sulfonic acid; In ethyl acetate; for 5h;Reflux;	3,4-dihydro-2H-Pyrane (0.42g, 5mmol) was added to a solution of <strong>[40598-94-5]3-bromo-1H-indazole</strong> (0.5g, 2.5mmol) in ethyl acetate (lOmL) with catalytic amount of PTSA (0.05g). The resulting reaction mass was stined and heated to reflux for 5h. The reaction mass was neutralized with aq. ammonia and diluted with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure and purified by silica gel column chromatography by eluting with 5% ethyl acetate-hexane to afford the title compound (0.4g, 51% ) LCMS: mlz = 283 (M+3).

With toluene-4-sulfonic acid; In toluene; at 80℃; for 1h;

Reference Example 4; 3-Bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazoleTo a solution of [40598-94-5]3-bromo-1H-indazole (500 mg) synthesized according to a method of the literature (V> Auwers, et al., J. Prakt. Chem., 1924, 314) in toluene (25 mL, manufactured by Wako Pure Chemical Industries, Ltd.), 3,4-dihydro-2H-pyrane (640 mg, manufactured by Tokyo Chemical Industry Co., Ltd.) and p-toluenesulfonic acid monohydrate (10 mg, manufactured by Wako Pure Chemical Industries, Ltd.) were added, and the mixture was heated for one hour at 80 C. The reaction solution was cooled to room temperature, and then a saturated aqueous solution of sodium hydrogen carbonate (10 mL) was added thereto. The mixture was extracted with ethyl acetate (3×20 mL), washed with brine (40 mL), and dried (MgSO4), and the solvent was evaporated. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1), to give 570 mg of the title compound. LC-MS: HPLC retention time 4.93 minutes, m/z 281 (M+H), condition B-1.

Reference： [1]Patent: WO2015/74081,2015,A1 .Location in patent: Paragraph 00388
[2]Journal of Medicinal Chemistry,2017,vol. 60,p. 2361 - 2372
[3]Organic Letters,2018,vol. 20,p. 4875 - 4879
[4]Synthesis,2011,p. 2651 - 2663
[5]Organometallics,2015,vol. 34,p. 4775 - 4780
[6]European Journal of Medicinal Chemistry,2019,vol. 177,p. 269 - 290
[7]Patent: WO2016/193939,2016,A1 .Location in patent: Page/Page column 84
[8]Patent: US2010/29733,2010,A1 .Location in patent: Page/Page column 37

23
N-[(1R)-1-(4-bromo-2-fluorophenyl)ethyl]acetamide [ No CAS ]
[ 40598-94-5 ]
[ 1259568-29-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 7011 - 7014

24
[ 40598-94-5 ]
[ 100-39-0 ]
[ 29985-03-3 ]

Yield	Reaction Conditions	Operation in experiment
50%		3-bromo-1 H-indazole (90.4 g, 0.459 mol, 1.0 eq.) and toluene (450 ml_) were placed in a 1 litre flask fitted with a mechanical stirrer under an atmosphere of nitrogen. Then potassium t-butoxide (t-BuOK, 54.2 g, 0.483 mol, 1.05 eq.) was added at room temperature over about half an hour and benzyl bromide (86.3 g, 0.505 mol, 1.1 eq.) was added over approximately 1.5 hours. The mixture was left stirred at the same temperature until the reaction was complete (checked by TLC, approximately 3 hours). Then 0.1 M HCI (45 ml_) and water (90 ml_) were added and the resulting phases were separated. The organic phase was washed with water, and the solvent was evaporated off at reduced pressure in order to obtain a red oily residue. The product was then precipitated through the addition of n-heptane, filtered and dried under vacuum at room temperature. Yield: 65.9 g of beige solid (yield 50%).1H NMR (300 MHz, DMSO-d6) delta (ppm) 5.67 (s, 2H), 7.29 (m, 6H), 7.50 (ddd, 1 H, J = 8.6 Hz, 6.9 Hz, 1.0 Hz), 7.60 (dd, 1 H, J = 8.2 Hz, 0.7 Hz), 7.80 (dd, 1 H, J = 8.6 Hz, 0.7 Hz).13C NMR (300 MHz, DMSO-d6) delta (ppm) 52.2, 1 10.4, 1 19.5, 121 .7, 122.9, 127.4, 127.4, 127.6, 127.7, 128.6, 128.6, 129.6, 136.9, 140.5.
50%		3-bromo-1 H-indazole (90.4 g, 0.459 mol, 1.0 eq.) and toluene (450 ml_) were placed in a 1 litre flask fitted with a mechanical stirrer under an atmosphere of nitrogen. Then potassium t-butoxide (t-BuOK, 54.2 g, 0.483 mol, 1.05 eq.) was added at room temperature over about half an hour and benzyl bromide (86.3 g, 0.505 mol, 1.1 eq.) was added over approximately 1.5 hours. The mixture was left stirred at the same temperature until the reaction was complete (checked by TLC, approximately 3 hours). Then 0.1 M HCI (45 mL) and water (90 mL) were added and the resulting phases were separated. The organic phase was washed with water, and the solvent was evaporated off at reduced pressure in order to obtain a red oily residue. The product was then precipitated through the addition of n-heptane, filtered and dried under vacuum at room temperature. Yield: 65.9 g of beige solid (yield 50%).1H NMR (300 MHz, DMSO-d6) delta (ppm) 5.67 (s, 2H), 7.29 (m, 6H), 7.50 (ddd, 1 H, J = 8.6 Hz, 6.9 Hz, 1.0 Hz), 7.60 (dd, 1 H, J = 8.2 Hz, 0.7 Hz), 7.80 (dd, 1 H, J = 8.6 Hz, 0.7 Hz).13C NMR (300 MHz, DMSO-d6) delta (ppm) 52.2, 110.4, 119.5, 121.7, 122.9, 127.4, 127.4, 127.6, 127.7, 128.6, 128.6, 129.6, 136.9, 140.5

Reference： [1]Patent: WO2011/15501,2011,A1 .Location in patent: Page/Page column 21
[2]Patent: WO2011/15502,2011,A1 .Location in patent: Page/Page column 18

25
[ 40598-94-5 ]
[ 131427-21-9 ]

Reference： [1]Patent: WO2011/15501,2011,A1
[2]Patent: WO2011/15502,2011,A1

26
[ 40598-94-5 ]
1-benzyl-3-chloromethyl-1H-indazole [ No CAS ]

Reference： [1]Patent: WO2011/15501,2011,A1
[2]Patent: WO2011/15502,2011,A1

27
[ 40598-94-5 ]
[ 130641-38-2 ]

Reference： [1]Patent: WO2011/15501,2011,A1
[2]Patent: WO2011/15502,2011,A1

28
[ 40598-94-5 ]
C₂₁H₂₄N₂O₃ [ No CAS ]

Reference： [1]Patent: WO2011/15501,2011,A1
[2]Patent: WO2011/15502,2011,A1

29
[ 40598-94-5 ]
[ 1339955-84-8 ]

Reference： [1]Synthesis,2011,p. 2651 - 2663

30
[ 40598-94-5 ]
[ 1339955-85-9 ]

Reference： [1]Synthesis,2011,p. 2651 - 2663

31
[ 40598-94-5 ]
[ 1339955-86-0 ]

Reference： [1]Synthesis,2011,p. 2651 - 2663

32
[ 40598-94-5 ]
[ 1339955-87-1 ]

Reference： [1]Synthesis,2011,p. 2651 - 2663

33
[ 40598-94-5 ]
[ 1339955-88-2 ]

Reference： [1]Synthesis,2011,p. 2651 - 2663

34
[ 40598-94-5 ]
[ 1339955-89-3 ]

Reference： [1]Synthesis,2011,p. 2651 - 2663

35
[ 40598-94-5 ]
[ 1339955-90-6 ]

Reference： [1]Synthesis,2011,p. 2651 - 2663

36
[ 40598-94-5 ]
[ 1339955-91-7 ]

Reference： [1]Synthesis,2011,p. 2651 - 2663

37
[ 40598-94-5 ]
[ 1339955-92-8 ]

Reference： [1]Synthesis,2011,p. 2651 - 2663

38
[ 40598-94-5 ]
[ 1339955-93-9 ]

Reference： [1]Synthesis,2011,p. 2651 - 2663

39
[ 40598-94-5 ]
3-(4-benzylpiperazin-1-yl)-1H-indazole [ No CAS ]

Reference： [1]Synthesis,2011,p. 2651 - 2663

40
[ 40598-94-5 ]
[ 1339956-01-2 ]

Reference： [1]Synthesis,2011,p. 2651 - 2663

41
[ 40598-94-5 ]
[ 835-42-7 ]

Reference： [1]Synthesis,2011,p. 2651 - 2663

42
[ 776-04-5 ]
[ 40598-94-5 ]
[ 1392808-92-2 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In dichloromethane; at 20℃; for 3h;	To a suspension of <strong>[40598-94-5]3-bromoindazole</strong> (500 mg, 2.54 mmol) in 8 ml CH2Cl2 was added triethyl amine (1.06 ml, 7.61 mmol) at room temperature. To this yellow solution was added 2-(trifluoromethyl)benzenesulfonyl chloride (0.392 ml, 2.54 mmol) and the reaction mixture was stirred for 3 h at room temperature. The reaction mixture was concentrated under reduced pressure and the residue was purified on SiO2 using 5% to 20% ethyl acetate in heptane to give 3-bromo-1-(2-(trifluoromethyl)phenylsulfonyl)-1H-indazole (894 mg)

Reference： [1]Patent: EP2487159,2012,A1 .Location in patent: Page/Page column 15

43
[ 69360-26-5 ]
[ 40598-94-5 ]
[ 1392809-20-9 ]

Reference： [1]Patent: WO2012/106995,2012,A1
[2]Patent: EP2487159,2012,A1

44
[ 69360-26-5 ]
[ 40598-94-5 ]
[ 1409955-76-5 ]

Yield	Reaction Conditions	Operation in experiment
		Example 144-(l -(2-cyanophenylsulfonyl H-indazol-3-yl)benzoic acidi) To a solution of 3-bromo-iH-indazole (200 mg, 1.02 mmol) in 2 ml CH2CI2 was added triethylamine (308 mg, 3.05 mmol) and 2-cyanobenzene-l-sulfonyl chloride (205 mg, 1.02 mmol). The reaction mixture was stirred overnight at room temperature. After completion the reaction mixture was concentrated under reduced pressure and the product was purified on Si02 using 0% to 50% ethylacetate in heptane as the eluent to give 4-(-(2- cyanophenylsulfonyl H-indazol-3-yl)benzoic acid (360 mg) as a yellow solid
	With triethylamine; In n-heptane; dichloromethane; at 20℃;	To a solution of <strong>[40598-94-5]3-bromo-1H-indazole</strong> (200 mg, 1.02 mmol) in 2 ml CH2Cl2 was added triethylamine (308 mg, 3.05 mmol) and 2-cyanobenzene-1-sulfonyl chloride (205 mg, 1.02 mmol). The reaction mixture was stirred overnight at room temperature. After completion the reaction mixture was concentrated under reduced pressure and the product was purified on SiO2 using 0% to 50% ethylacetate in heptane as the eluent to give 4-(1-(2-cyanophenylsulfonyl)-1H-indazol-3-yl)benzoic acid (360 mg) as a yellow solid.

Reference： [1]Patent: WO2012/106995,2012,A1 .Location in patent: Page/Page column 70
[2]Patent: EP2487159,2012,A1 .Location in patent: Page/Page column 23

45
[ 40598-94-5 ]
[ 312-94-7 ]
[ 1392808-92-2 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In dichloromethane; at 20℃; for 3h;	1,1,1 ,3 ,3-hexafluoro-2-(4-(l -(2-(trifluorometliyl)plienylsulfonyl)-iH-indazol-3- yl)phenyl)propan-2-oli) To a suspension of <strong>[40598-94-5]3-bromoindazole</strong> (500 mg, 2.54 mmol) in 8 ml CH2CI2 was added triethyl amine (1.06 ml, 7.61 mmol) at room temperature. To this yellow solution was added 2-(trifluoromethyl)benzenesulfonyl chloride (0.392 ml, 2.54 mmol) and the reaction mixture was stirred for 3 h at room temperature. The reaction mixture was concentrated under reduced pressure and the residue was purified on Si02 using 5% to 20% ethyl acetate in heptane to give 3-bromo-l-(2-(trifluoromethyl)phenylsulfonyl)-iH-indazole (894 mg)

Reference： [1]Patent: WO2012/106995,2012,A1 .Location in patent: Page/Page column 61-62

46
[ 40598-94-5 ]
[ 4659-45-4 ]
[ 1392808-81-9 ]

Yield	Reaction Conditions	Operation in experiment
	pyridine; at 1℃; for 150h;	ExamplesExample 14-(l-(2,6-dichlorobenzoyl H-indazol-3-yl)benzoic acidi) A solution of 3-bromo-4-azaindole (100 mg, 0.508 mmol) and 2,6-dichlorobenzoyl chloride (159 mg, 0.761 mmol) in 4 ml of pyridine was stirred for 1 h at 150 C in a microwave reactor. After cooling to room temperature the reaction mixture was diluted with water and the product was extracted into CH2CI2. The organic layer was washed with water, dried over a phase separation filter and concentrated under reduced pressure. The residue was purified on S1O2, using 10% ethylacetate in heptane as the eluent, to give (3-bromo-7H-indazol- 1 -yl)(2,6- dichlorophenvDmethanone (140 mg) as a yellow solid.
	With pyridine; at 150℃; for 1h;Microwave;	A solution of 3-bromo-4-azaindole (100 mg, 0.508 mmol) and 2,6-dichlorobenzoyl chloride (159 mg, 0.761 mmol) in 4 ml of pyridine was stirred for 1 h at 150 C in a microwave reactor. After cooling to room temperature the reaction mixture was diluted with water and the product was extracted into CH2Cl2. The organic layer was washed with water, dried over a phase separation filter and concentrated under reduced pressure. The residue was purified on SiO2, using 10% ethylacetate in heptane as the eluent, to give (3-bromo-1H-indazol-1-yl)(2,6-dichlorophenyl)methanone (140 mg) as a yellow solid.

Reference： [1]Patent: WO2012/106995,2012,A1 .Location in patent: Page/Page column 57-58
[2]Patent: EP2487159,2012,A1 .Location in patent: Page/Page column 11
[3]ACS Medicinal Chemistry Letters,2020,vol. 11,p. 114 - 119

47
[ 40598-94-5 ]
[ 1392808-80-8 ]

Reference： [1]Patent: WO2012/106995,2012,A1
[2]Patent: EP2487159,2012,A1
[3]ACS Medicinal Chemistry Letters,2020,vol. 11,p. 114 - 119

48
[ 40598-94-5 ]
[ 1392809-08-3 ]

Reference： [1]Patent: WO2012/106995,2012,A1

49
[ 40598-94-5 ]
[ 1392808-82-0 ]

Reference： [1]Patent: WO2012/106995,2012,A1
[2]Patent: EP2487159,2012,A1
[3]ACS Medicinal Chemistry Letters,2020,vol. 11,p. 114 - 119

50
[ 40598-94-5 ]
methyl 4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-1H-indazol-3-yl)benzoate [ No CAS ]

Reference： [1]Patent: WO2012/106995,2012,A1

51
[ 40598-94-5 ]
sodium 4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-1H-indazol-3-yl)benzoate [ No CAS ]

Reference： [1]Patent: WO2012/106995,2012,A1

52
[ 40598-94-5 ]
5-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-1H-indazol-3-yl)isobenzofuran-1(3H)-one [ No CAS ]

Reference： [1]Patent: WO2012/106995,2012,A1

53
[ 40598-94-5 ]
benzyl 4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-1H-indazol-3-yl)-2-(hydroxymethyl)benzoate [ No CAS ]

Reference： [1]Patent: WO2012/106995,2012,A1

54
[ 40598-94-5 ]
benzyl 4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-1H-indazol-3-yl)-2-formylbenzoate [ No CAS ]

Reference： [1]Patent: WO2012/106995,2012,A1

55
[ 40598-94-5 ]
benzyl 4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-1H-indazol-3-yl)-2-(difluoromethyl)benzoate [ No CAS ]

Reference： [1]Patent: WO2012/106995,2012,A1

56
[ 40598-94-5 ]
4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-1H-indazol-3-yl)-2-(difluoromethyl)benzoic acid [ No CAS ]

Reference： [1]Patent: WO2012/106995,2012,A1

57
[ 2905-27-3 ]
[ 40598-94-5 ]
[ 1392809-29-8 ]

Reference： [1]Patent: WO2012/106995,2012,A1
[2]Patent: EP2487159,2012,A1

58
[ 2905-27-3 ]
[ 40598-94-5 ]
[ 1392809-40-3 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 20℃; for 2h;	Example 174-(l-(3,5-dimethylphenylsulfonyl)-lH-indazol-3-yl)-3-fluorobenzoic acid i) 3-bromo-iH-indazole (3 gram; 15 mmol) was dissolved in 30 ml DMF, followed by the addition of sodiumhydride (850 mg, 21 mmol). After stirring for 20 min at room temperature, 3,5-dimethylbenzene-l-sulfonyl chloride (4.4 gram, 21 mmol) was added and the reaction mixture was stirred for another 2 h at room temperature. The reaction was quenched by the addition of water and the formed solids were filtered off and washed with little methanol. The solids were dried to obtain 3-bromo-l-(3,5-dimethylphenylsulfonyl)-lH-indazole (2.1 gram) as a white solid.
		<strong>[40598-94-5]3-bromo-1H-indazole</strong> (3 gram; 15 mmol) was dissolved in 30 ml DMF, followed by the addition of sodiumhydride (850 mg, 21 mmol). After stirring for 20 min at room temperature, 3,5-dimethylbenzene-1-sulfonyl chloride (4.4 gram, 21 mmol) was added and the reaction mixture was stirred for another 2 h at room temperature. The reaction was quenched by the addition of water and the formed solids were filtered off and washed with little methanol. The solids were dried to obtain 3-bromo-1-(3,5-dimethylphenylsulfonyl)-1H-indazole (2.1 gram) as a white solid.

Reference： [1]Patent: WO2012/106995,2012,A1 .Location in patent: Page/Page column 74
[2]Patent: EP2487159,2012,A1 .Location in patent: Page/Page column 26

59
2-chloro-6-(trifluoromethyl)benzoyl chloride [ No CAS ]
[ 40598-94-5 ]
(3-bromo-1H-indazol-1-yl)(2-chloro-6-(trifluoromethyl)phenyl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	With dmap; triethylamine; In dichloromethane; at 20℃; for 3h;	To a solution of 3-bromo-lH-indazole (F-1) (200 mg, 1.02 mmol) in DCM (20 mL) was added DMAP (12.5 mg, 0.1 mmol), TEA (0.3 mL, 2 mmol), 2-chloro-6-(trifluoromethyl)benzoyl chloride (370 mg, 1.53 mmol) in DCM (5 mL) was added slowly, the reaction mixture was stirred at RT for 3 h, then diluted with EA (100 mL), washed with Sat. NaHC03 aqueous, water and brine, concentrated and purified with flash chromatograph (PE:EA=10: 1) to give 400 mg (99%) of title compound as a yellow solid. LCMS (ESI) calc'd for Ci5H7BrClF3N20 [M+H]+, 402.9, found: 403, 405.
99%	With dmap; triethylamine; In dichloromethane; at 20℃; for 3h;	To a solution of <strong>[40598-94-5]3-bromo-1H-indazole</strong> (F-i) (200 mg, 1.02 mmol) in DCM (20 mL) was added DMAP (12.5 mg, 0.1 mmol), TEA (0.3 mL, 2 mmol), followed by the addition of 2-chloro-6-(trifluoromethyl)benzoyl chloride (370 mg, 1.53 mmol) in DCM (5mL) slowly. The reaction mixture was stirred at room temperature for 3 h, then diluted with EA (100 mL), washed with sat.NaHCO3 aqueous, water and brine, concentrated, and purified with flash chromatography (PE :EA= 10:1) to give 400 mg (99%) of the title compound as ayellow solid. LCMS (ESI) calc?d for C15H7BrClF3N2O [M+H], 402.9, found: 403, 405.
	With triethylamine;dmap; In dichloromethane; at 20℃; for 24h;	Example 24B: Preparation of sodium 4-(l-(2-chloro-6-(trifluoromethyl)benzoyl) indazol-3- yl)benzoate (24B)B-4 24E i) Preparation of (3-bromo-/H-indazol-l-yl)(2-chloro-6-(trifluoromethyl) phenyl)methanone (B-2). To a solution of 3-bromo-iH-indazole (2 g, 0.75mmol), DMAP (1 g, 8.5 mmol) and Et3N (1.85 ml, 12.7 mmol) in CH2CI2 (20 mL) at 0 C was added a solution of compound A-3 (4 g, 20.4 mmol) in CH2CI2 (5 mL). The mixture was stirred at rt for 24 h, diluted with CH2CI2, washed with 1M HC1. The organic layer was washed with sat. NaHC03 and brine, dried over anhydrous Na2S04 and concentrated. The residue was purified by flash chromatography (PE/EA=10/1) to give the title compound. LCMS (ESI) calc'd for Ci5H8BrClF3N20 [M+H]: 404.9, Found: 404.9.

Reference： [1]Patent: WO2014/26327,2014,A1 .Location in patent: Page/Page column 73
[2]Patent: WO2014/28589,2014,A2 .Location in patent: Page/Page column 71; 93; 94
[3]Patent: WO2012/106995,2012,A1 .Location in patent: Page/Page column 83

60
[ 40598-94-5 ]
[ 1403488-80-1 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 9735 - 9750

61
[ 40598-94-5 ]
[ 1403488-91-4 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 9735 - 9750

62
[ 23133-37-1 ]
[ 40598-94-5 ]
[ 1403488-90-3 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 9735 - 9750

63
[ 40598-94-5 ]
[ 1562453-66-0 ]

Reference： [1]Patent: WO2014/26327,2014,A1
[2]Patent: WO2014/28589,2014,A2

64
[ 40598-94-5 ]
[ 1562453-71-7 ]

Reference： [1]Patent: WO2014/26327,2014,A1
[2]Patent: WO2014/28589,2014,A2

65
[ 40598-94-5 ]
[ 1562449-98-2 ]

Reference： [1]Patent: WO2014/26327,2014,A1
[2]Patent: WO2014/28589,2014,A2

66
[ 1561771-96-7 ]
[ 40598-94-5 ]
[ 1562995-63-4 ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; triethylamine; In dichloromethane; at 20℃;	A mixture of 2-chloro-6-cyclopropylbenzoic acid (0.23 g, 1.17 mol) and (COCl)2 (0.2 mL,2.34 mol) in DCM (10 mL) and DMF (5 drops) was stirred at room temperature for 1.5h. The solvent was removed and the residue was dissolved in DCM (10 mL).To a mixture of <strong>[40598-94-5]3-bromo-1H-indazole</strong> (0.23 g, 1.17 mol), DMAP (74 mg, 0.59 mol) and Et3N (0.32 mL, 2.34 mol) in DCM (10 mL) was added the above DCM solution dropwise, and thereaction mixture was stirred at room temperature overnight. The resulting solution was diluted with H20 (50 mL), and the aqueous layer was extracted with DCM (30 mLx3). The combined organic layers were washed with brine (30 mL), dried over anhydrous Na2SO4 and concentrated. The residue was chromatographed on silica gel (PE:EA 10:1) to obtain the title compound as a white solid. LCMS (ESI) calc?d for C17H12BrClN2O [M+H]: 375, found: 375.

Reference： [1]Patent: WO2014/28589,2014,A2 .Location in patent: Page/Page column 73; 74

67
[ 40598-94-5 ]
3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole [ No CAS ]

Reference： [1]Patent: WO2014/134772,2014,A1
[2]Patent: WO2014/137719,2014,A1
[3]Journal of Medicinal Chemistry,2017,vol. 60,p. 2983 - 2992
[4]Patent: WO2018/64119,2018,A1
[5]Patent: WO2019/215203,2019,A1

68
[ 40598-94-5 ]
4-(6-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-3-yl)pyrimidin-4-yl)morpholine [ No CAS ]

Reference： [1]Patent: WO2014/134772,2014,A1
[2]Patent: WO2014/137719,2014,A1
[3]Journal of Medicinal Chemistry,2017,vol. 60,p. 2983 - 2992

69
[ 40598-94-5 ]
C₁₅H₁₅N₅O [ No CAS ]

Reference： [1]Patent: WO2014/134772,2014,A1

70
[ 76513-69-4 ]
[ 40598-94-5 ]
3-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66.21%		[1066] to a cold (0 C), stirred solution of <strong>[40598-94-5]3-bromo-1H-indazole</strong> (5 g, 25.38 mmol) in DMF(130 ml) was added NAH (1.22 g, 50.76 mmol) in portions. After 0.2h, sem-c1 (5.08 g, 30.46 mmol) was added and then the mixture was stirred at 25 C for 6 hours under N2 atmosphere. The reaction was quenched with a saturated aqueous solution of nh4ci and the resulting layer was extracted with EtOAc (100 ml x 2). The combined organic layers were dried, filtered and concentrated under reduced pressure to leave a residue. The residue which was purified by flash chromatography on silica (elution with 100: 1 to 10: 1 petroleum ether : EtOAc ) to give compound compound 197a (5.5 g, 66.21% yield) as an oil. 1H NMR (CDCl3, 400 mhz): delta 7.71 - 7.69 (m, 1h), 7.65 - 7.60 (m, 1h), 7.57 - 7.51 (m, 1h), 7.37 - 7.29 (m, 1h), 5.76 (d, = 3.2 hz, 2h), 3.70 -3.55 (m, 2h), 1.02 - 0.87 (m, 2h), 0.00 (d, = 3.2 hz, 9h). MS (ESI) m/z (M+H)+ 338.3.
52.1%		3-Bromo-lH-indazole (5 g, 25.38 mmol) was stirred as a suspension in DMF (100 ml) under nitrogen then cooled to 0C. Sodium hydride (60% dispersion in mineral oil) (1.218 g, 30.45 mmol) was added portion-wise and the reaction was stirred at 0C for 15 minutes. (2-(chloromethoxy)ethyl)trimethylsilane (5.39 ml, 30.45 mmol) was added drop-wise then the reaction was allowed to reach room temperature over 16 hours. The reaction was quenched with NH4CI (50 ml) and diluted with water (300 ml) and ethyl acetate (300 ml). The layers were separated and the organic phase was washed with water (2 x 200 ml), passed through a phase separator cartridge and concentrated under reduced pressure to afford a brown oil. The oil was purified by flash silica chromatography, elution gradient of 0-10% EtOAc in heptanes to afford 3-bromo-l-[2-(trimethylsilyl)ethoxy]methyl}-lH-indazole (4.33 g, 52.1%) as a white solid. 1H NMR (400 M Hz, CDCI3, 30C) -0.00 (9H, s), 0.9 - 0.99 (2H, m), 3.57 - 3.69 (2H, m), 5.75 (2H, s), 7.26 - 7.37 (1H, m), 7.53 (1H, ddd), 7.62 (1H, d), 7.67 - 7.76 (1H, m).
		Step 1: To a cold (0 C), stirred solution of <strong>[40598-94-5]3-bromoindazole</strong> (1.0 g, 5.08 mmol) in DMF (25 mL) was added NaH (0.24 g of 60% in oil, 6.09 mmol) in portions. After 15 min, SEMC1 (1.08 mL, 6.09 mmol) was added and the mixture was stirred at room temperature overnight. The reaction was quenched with a saturated aqueous solution of NH4CI and the resulting layer was extracted with EtOAc (x2). The combined organic layers were dried, filtered and concentrated under reduced pressure to leave a residue which was purified by flash chromatography on silica (elution with 100: 1 to 10: 1 hexane:EtOAc) to yield the desired product as an oil.

To a cold (0 C), stirred solution of [40598-94-5]3-bromoindazole (1.0 g, 5.08 mmol) in DMF (25 mL) was added NaH (0.24 g of 60% in oil, 6.09 mmol) in portions. After 15 min, SEMCI (1.08 mL, 6.09 mmol) was added and the mixture was stirred at room temperature overnight. The reaction was quenched with a saturated aqueous solution of NH4C1 and the resulting layer was extracted with EtOAc (x2). The combined organic layers were dried, filtered and concentrated under reduced pressure to leave a residue which was purified by flash chromatography on silica (elution with 100: 1 to 10: 1 hexane:EtOAc) to yield the desired product as an oil.

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 2983 - 2992
[2]Patent: WO2018/64119,2018,A1 .Location in patent: Paragraph 1066
[3]Patent: WO2019/215203,2019,A1 .Location in patent: Page/Page column 60-61
[4]Patent: WO2014/134772,2014,A1 .Location in patent: Page/Page column 115
[5]Patent: WO2014/137719,2014,A1 .Location in patent: Page/Page column 119

71
[ 40598-94-5 ]
[ 1692-25-7 ]
[ 1310207-72-7 ]

Reference： [1]Journal of Organic Chemistry,2014,vol. 79,p. 8871 - 8876

72
[ 40598-94-5 ]
(R)-1-(1H-indazol-3-yl)-2-phenylmethanesulfonyl-1,2,3,4-tetrahydroisoquinoline [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2015,vol. 96,p. 196 - 208
[2]Patent: US2018/57483,2018,A1

73
[ 40598-94-5 ]
3-[(R)-[2-(2-benzyloxyethyl)phenyl]-((R)-2-methylpropane-2-sulfinylamino)methyl]indazole-1-carboxylic acid tert-butyl ester [ No CAS ]