[ CAS No. 253801-04-6 ] {[proInfo.proName]}

Name: 253801-04-6|1H-Indazole-5-carbaldehyde|97%
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Quality Control of [ 253801-04-6 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 253801-04-6 ]

CAS No. :	253801-04-6	MDL No. :	MFCD06738280
Formula :	C₈H₆N₂O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	YJKMYHNMBGQQQZ-UHFFFAOYSA-N
M.W :	146.15	Pubchem ID :	21250644
Synonyms :

Calculated chemistry of [ 253801-04-6 ]

Physicochemical Properties

Num. heavy atoms :	11
Num. arom. heavy atoms :	9
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	41.48
TPSA :	45.75 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) :	-6.37 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.69
Log Po/w (XLOGP3) :	1.15
Log Po/w (WLOGP) :	1.38
Log Po/w (MLOGP) :	0.49
Log Po/w (SILICOS-IT) :	2.17
Consensus Log Po/w :	1.18

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.01
Solubility :	1.43 mg/ml ; 0.00977 mol/l
Class :	Soluble
Log S (Ali) :	-1.71
Solubility :	2.88 mg/ml ; 0.0197 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.84
Solubility :	0.213 mg/ml ; 0.00146 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.03

Safety of [ 253801-04-6 ]

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

Application In Synthesis of [ 253801-04-6 ]

* 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 [ 253801-04-6 ]
Downstream synthetic route of [ 253801-04-6 ]

[ 253801-04-6 ] Synthesis Path-Upstream 1~7

1
[ 253801-04-6 ]
[ 74626-47-4 ]

Reference： [1] Synlett, 2011, # 15, p. 2223 - 2227

2
[ 53857-57-1 ]
[ 68-12-2 ]
[ 253801-04-6 ]

Yield	Reaction Conditions	Operation in experiment
51%	Stage #1: With sodium hydride In tetrahydrofuran at 20℃; for 0.416667 h; Stage #2: With sec.-butyllithium In tetrahydrofuran; cyclohexane at -70 - -60℃; for 2 h;	A) Preparation of Intermediate Products; Intermediate Product 1: 1H-indazole-5-carbaldehyde; 2.60 g (65.00 mmol) sodium hydride (60percent in mineral oil) was added batchwise to a solution of 11.64 g (59.08 mmol) 5-bromo-1H-indazole in 150 mL THF under argon within 10 minutes and the mixture was stirred for 15 minutes at RT. The reaction mixture was cooled to -70° C. and within 30 minutes 100.00 mL (130.00 mmol) sec-butyllithium (1.3 M in cyclohexane) were added dropwise, while the temperature was kept below -60° C. The mixture was stirred for a further 2 h at -70° C. and then a solution of 20.00 mL (0.260 mol) DMF in 20 mL THF was added dropwise, while the temperature was kept below -50° C. The reaction mixture was slowly heated to RT and stirred for 16 h. Then the mixture was slowly cooled to 0° C. and slowly 180 mL of 2N aqueous HCl was added dropwise, the mixture was stirred for a further 15 minutes and the pH was adjusted to 9-10 with sat. aqueous sodium bicarbonate solution. The aqueous phase was exhaustively extracted with EtOAc, the combined org. phases were dried over magnesium sulphate and evaporated down i. vac. Column chromatography (silica gel, petroleum ether/EtOAc 1:1 v/v), trituration with hexane and drying i. vac. at 50° C. yielded the product. Yield: 4.40 g (51percent of theory) R_f=0.37 (silica gel, petroleum ether/EtOAc 1/1 v/v) ESI-MS: (M+H)⁺=147

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 16, p. 4482 - 4485
[2] Patent: WO2005/84672, 2005, A1, . Location in patent: Page/Page column 40-41
[3] Patent: US2005/227968, 2005, A1, . Location in patent: Page/Page column 15-16
[4] Patent: WO2008/154241, 2008, A1, . Location in patent: Page/Page column 67

3
[ 53857-57-1 ]
[ 253801-04-6 ]

Yield	Reaction Conditions	Operation in experiment
57%	Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -40℃; for 0.25 h; Stage #2: With N,N-dimethyl-formamide In tetrahydrofuran; hexane at -40 - 20℃; for 1.5 h;	1H-INDAZOLE-5-CARBALDEHYDE (57) To a solution of commercially available 5- bromoindazole (0.5 g, 2.53 mmol) in dry THF (10 ml) was added 2.5 M solution of n-BuLi in hexane (6.42 mmol) at-40 C and under argon atmosphere. After 15 minute of stirring at this temperature, DMF (0.4 ml, 5.06 mmol) was added and the mixture stirred for additional 30 minutes AT-40 C. The cold bath was then removed and the mixture was allowed to stir for one hrs at room temeperature. Water (30 ml) was added and the aqueous layer was extracted with EtOAc (2X30 ml). The organic layer was washed with brine, dried (NA2S04) and concentrated to give 0.54 g of crude 57 that was purified on silica gel to give 0.21 g (57percent yield) aldehyde 57. 'H NMR (400 MHz, CDCL3) : 8 7.62 (dd, 1H), 7.98 (d, 1H), 8.35 (M, 2H), 10.11 (s, 1H), 10. 59 (br. S, 1H) ppm.

Reference： [1] Patent: WO2005/813, 2005, A1, . Location in patent: Page 36
[2] Patent: US6313110, 2001, B1,

4
[ 68-12-2 ]
[ 253801-04-6 ]

Yield	Reaction Conditions	Operation in experiment
52%	Stage #1: With n-butyllithium In tetrahydrofuran at -78 - -40℃; for 1 h; Stage #2: at -78 - 20℃; for 2.5 h; Stage #3: With water In tetrahydrofuran	Example 1; Synthesis of 4-(lH-indazol-5-yl)-6-(4-phenoxyphenyl)pwimidin-2(lH)-one; STEP 1:; [0198] lH-indazole-5-carbaldehyde (2). w-Butyllithium (35.0 mL, 87.5 mmol) was added slowly to 5-bromoindazole (1, 4.98 g, 25.3 mmol) in THF (60 mL) at -78⁰C. After 30 min, the solution was warmed to -4O⁰C over 30 min and then cooled to -78⁰C. DMF (3.1 mL, 77.5 mmol) was added. After 15 min, the reaction flask was removed from the dry ice/acetone bath and stirred at room temperature for 2.5 h. The solution was quenched with H₂O. The aqueous layer was extracted with EtOAc. The organic layer was washed with H₂O and brine, dried over Na₂SO₄, filtered and concentrated to a golden oil. The crude material was purified by column chromatography (0-100percent EtOAc/hexanes) to give 2 as a light yellow solid (1.91 g, 52percent yield). LCMS m/z 147.0 (MH⁺), R, 1.53 min.[0199] Reference for the synthesis of lH-indazole-5-carbaldehyde: E. Piatnitski, WO 2005/000813 p 37.

Reference： [1] Patent: WO2007/124288, 2007, A1, . Location in patent: Page/Page column 50

5
[ 201230-82-2 ]
[ 55919-82-9 ]
[ 141-53-7 ]
[ 253801-04-6 ]

Yield	Reaction Conditions	Operation in experiment
59%	at 110℃; for 6 h;	A mixture of 5-iodoindazole (10 g, 41 mmol) , HCOONa (5.57 g, 82 mmol) and PdCI₂(PPh₃J₂ (1.44 g, 2.05 mmol) in DMF (60 mL) was put under vacuum and charged with carbon monoxide (CO). This process was repeated three times, after which the mixture was kept at 110 ⁰C for 6 hr. After cooling to room temperature (rt), the reaction mixture was diluted with brine and extracted with EtOAc. The organic phases were combined, washed with brine, dried, and concentrated. The crude product was purified by column chromatography to afford 1 H-indazole-5-carboxaldehyde (3.52 g, 59percent) as a white solid.

Reference： [1] Patent: WO2008/71451, 2008, A1, . Location in patent: Page/Page column 47

6
[ 74626-47-4 ]
[ 253801-04-6 ]

Reference： [1] Patent: US6200978, 2001, B1,

7
[ 88990-57-2 ]
[ 253801-04-6 ]

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 19, p. 5442 - 5447

[ 253801-04-6 ] Synthesis Path-Downstream 1~88

1
[ 253801-04-6 ]
[5-(5-amino-3-methyl-3H-imidazol-4-yl)-[1,3,4]oxadiazol-2-yl]-(4-chloro-phenyl)-amine [ No CAS ]
(4-chloro-phenyl)-(5-{5-[(1H-indazol-5-ylmethylene)-amino]-3-methyl-3H-imidazol-4-yl}-[1,3,4]oxadiazol-2-yl)-amine [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 1440 - 1444

2
[ 253801-04-6 ]
[ 883556-81-8 ]
[ 883557-47-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 1913 - 1919

3
[ 253801-04-6 ]
[ 5031-78-7 ]
4-(1H-indazol-5-yl)-6-(4-phenoxyphenyl)pyrimidin-2(1H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		STEP 2:; a) Urea, /-PrOH, HCI b) Urea, delta [0200] 4-(lH-indazol-5-yl)-6-(4-phenoxyphenyl)pyrimidin-2(lH)-one (3). lH-Indazole-5-carbaldehyde (2, 0.27 g, 1.85 mmol) and urea (0.33 g, 5.45 mmol) were stirred overnight at room temperature in i-PrOH (18 mL) and HCl (cone, 1.8 mL). At that time, the viscous solution was divided into nine equal portions. To one portion was added 4'-phenoxyacetophenone (0.0531 g, 0.25 mmol) and additional urea. The reaction was heated at 8O0C overnight in a sealed vial. The reaction mixture was then cooled, <n="52"/>concentrated and purified by reverse phase HPLC to give 3 as the TFA salt (9.6 mg, 99% purity). LCMS m/z 381.1 (MH+), R, 2.39 min.

Reference： [1]Patent: WO2007/124288,2007,A1 .Location in patent: Page/Page column 50-51

4
[ 253801-04-6 ]
(5-{2-[2-(1H-indazol-5-yl)-ethyl]-pyridin-3-yl}-[1,3,4]oxadiazol-2-yl)-(3-trifluoromethyl-phenyl)-amine [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 1913 - 1919

5
[ 253801-04-6 ]
[ 24424-99-5 ]
[ 635713-71-2 ]

Yield	Reaction Conditions	Operation in experiment
99%	dmap; In acetonitrile; at 20℃; for 0.5h;	5-Formyl-indazole-1-carboxylic acid tert-butyl ester (58) To a solution of 57 (0.21 g, 1.43 mmol) in acetonitrile (10 ml) was added BOC anhydride (0.314 g, 1.43 mol) followed by catalytic amounts OF DMAP (0.03 g). After 30 minutes of stirring at room temperature, solvent was evaporated, EtOAc (30 ml) was added and the organic layer was washed with 0.5 N HCl solution (10 ml) and brine. It was then dried (NA2S04) and concentrated to give 0.35 g (99% yield) desired product that was used to prepare di-Boc-protected 3 without purification.
90%	With dmap; triethylamine; In dichloromethane;	5-Formyl-indazole-1-carboxylic acid tert-butyl ester A methylene chloride (2 mL) solution of di-tert-butyldicarbonate (388 mg, 1.78 mmol) was added dropwise at room temperature to a solution of <strong>[253801-04-6]1H-indazole-5-carbaldehyde</strong> (273 mg, 1.87 mmol), 4-dimethylaminopyridine (114 mg, 0.94 mmol), and triethylamine (0.26 mL, 1.87 mmol) in methylene chloride (10 mL). The resulting bright yellow solution was stirred at room temperature for 16 h. Solvents were removed in vacuo and the residue was subjected to flash chromatography with silica gel (25 g) and ethyl acetate/hexanes (1:1) containing 1% triethylamine as eluent to afford the title compound as a brownish yellow liquid (414 mg, 90%). 1H-NMR (CDCl3, 500 MHz) delta 10.08 (s, 1H), 8.38 (s, 1H), 8.34 (s, 1H), 8.25 (d, J=8.5 Hz, 1H), 8.04 (d, J=8.8 Hz, 1H), 1.71 (s, 9H). 13C-NMR (CDCl3, 125 MHz) delta 191.8, 149.0, 142.5, 140.6, 133.0, 128.3, 126.4, 125.8, 115.3, 85.7, 27.8.
90%	With dmap; triethylamine; In dichloromethane; at 20℃; for 16h;	A methylene chloride (2 [ML)] solution of di-tert-butyldicarbonate (388 mg, 1.78 mmol) was added dropwise at room temperature to a solution of 1H-indazole-5- carbaldehyde (273 mg, 1.87 mmol), [4-DIMETHYLAMINOPYRIDINE] (114 mg, 0.94 mmol), and triethylamine (0.26 mL, 1.87 mmol) in methylene chloride (10 mL). The resulting bright yellow solution was stirred at room temperature for 16 h. Solvents were removed in vacuo and the residue was subjected to flash chromatography with silica gel (25 g) and ethyl [ACETATE/HEXANES] [(1] : [1)] containing [1%] triethylamine as eluent to afford the title compound as a brownish yellow liquid (414 mg, [90%).'H-NMR] [(CDC13,] 500 MHz) [8] 10.08 (s, [1H),] 8. 38 (s, 1H), 8.34 (s, 1H), 8.25 (d, J = 8.5 Hz, 1H), 8.04 (d, J = 8.8 Hz, 1H), 1.71 (s, 9H). 13CNMR [(CDC13,] 125 MHz) 8 191.8, 149.0, 142.5, 140.6, 133.0, 128.3, 126.4, 125.8, 115.3, 85.7, 27.8.

90%

With dmap; triethylamine; In dichloromethane; at 20℃; for 16h;

A methylene chloride (2 mL) solution of di-tert-butyldicarbonate (388 mg, 1.78 mmol) was added dropwise at room temperature to a solution of [253801-04-6]1H-indazole-5-carbaldehyde (273 mg, 1.87 mmol), 4-dimethylaminopyridine (114 mg, 0.94 mmol), and triethylamine (0.26 mL, 1.87 mmol) in methylene chloride (10 mL). The resulting bright yellow solution was stirred at room temperature for 16 h. Solvents were removed in vacuo and the residue was subjected to flash chromatography with silica gel (25 g) and ethyl acetate/hexanes (1:1) containing 1% triethylamine as eluent to afford the title compound as a brownish yellow liquid (414 mg, 90%). 1H-NMR (CDCl3, 500 MHz) delta 10.08 (s, 1H), 8.38 (s, 1H), 8.34 (s, 1H), 8.25 (d, J=8.5 Hz, 1H), 8.04 (d, J=8.8 Hz, 1H), 1.71 (s, 9H). 13CNMR (CDCl3, 125 MHz) delta 191.8, 149.0, 142.5, 140.6, 133.0, 128.3, 126.4, 125.8, 115.3, 85.7, 27.8.

Reference： [1]Patent: WO2005/813,2005,A1 .Location in patent: Page 37
[2]Patent: US2004/204397,2004,A1
[3]Journal of Organic Chemistry,2008,vol. 73,p. 8502 - 8510
[4]Patent: WO2003/104236,2003,A1 .Location in patent: Page 60
[5]Patent: US2005/215576,2005,A1 .Location in patent: Page/Page column 20

6
[ 53857-57-1 ]
[ 253801-04-6 ]

Yield	Reaction Conditions	Operation in experiment
57%		1H-INDAZOLE-5-CARBALDEHYDE (57) To a solution of commercially available 5- bromoindazole (0.5 g, 2.53 mmol) in dry THF (10 ml) was added 2.5 M solution of n-BuLi in hexane (6.42 mmol) at-40 C and under argon atmosphere. After 15 minute of stirring at this temperature, DMF (0.4 ml, 5.06 mmol) was added and the mixture stirred for additional 30 minutes AT-40 C. The cold bath was then removed and the mixture was allowed to stir for one hrs at room temeperature. Water (30 ml) was added and the aqueous layer was extracted with EtOAc (2X30 ml). The organic layer was washed with brine, dried (NA2S04) and concentrated to give 0.54 g of crude 57 that was purified on silica gel to give 0.21 g (57% yield) aldehyde 57. 'H NMR (400 MHz, CDCL3) : 8 7.62 (dd, 1H), 7.98 (d, 1H), 8.35 (M, 2H), 10.11 (s, 1H), 10. 59 (br. S, 1H) ppm.
	With hydrogenchloride; sodium hydroxide; sodium hydrogensulfite; In tetrahydrofuran; N-methyl-acetamide; cyclohexane; water; ethyl acetate; mineral oil;	Preparation of 5-carboxaldehydeindazole. A flask was charged with 60% sodium hydride in mineral oil (20.5 g) and tetrahydrofuran (1.05 L) under nitrogen. A solution of 5-bromoindazole (91.0 g) in tetrahydrofuran (0.64 L) was added over 15 minutes and the mixture stirred another 15 minutes before cooling to -60 C. A solution of 1.3 N sec-buthyllithium in cyclohexane (0.750 L) was added at -60 to -40 C. over 19 minutes. The solution was stirred another hour at -40 to -50 C. A solution of dimethylformamide (160 mL) in tetrahydrofuran (200 mL) was charged at -45 to -40 C. over 12 minutes. The mixture was warmed to 25 C. over 5 h and recooled to 0 C. 1 N Hydrochloric acid (1.20 L) was added at <10 C. and the solution was made basic by adding back solid sodium bicarbonate. The layers were separated and the aqueous further extracted with ethyl acetate (20.65 L). The combined organic layers were washed with water (0.35 L). 5-Carboxaldehydeindazole, 14, was extracted from the organic solution by washes with 0.6 N sodium bisulfite solution in water (30.65 L). The combined extracts were backwashed with ethyl acetate (0.225 L) and the pH was adjusted to 10 by the addition of 5 N sodium hydroxide (0.21 L used). 5-Carboxaldehydeindazole was extracted into ethyl acetate (3*0.50 L). The combined extracts were dried over magnesium sulfate (3 g) and filtered through a pad of silica gel (50 g) with ethyl acetate. The eluant was concentrated by rotary evaporation, adding a total of 0.30 L heptane during the distillation. The solid was filtered, washed with heptane (0.50 L) and dried under vacuum at 45 C. to produce 54.6 g of 14 (78% yield). The solids contain 2 wgt % ethyl acetate.

Reference： [1]Patent: WO2005/813,2005,A1 .Location in patent: Page 36
[2]Patent: US6313110,2001,B1

Yield	Reaction Conditions	Operation in experiment
		Aldehyde preparation: The aldehyde was prepared according to : DeLucca, G. V. US 6313110 B1 (11/6/2001). Data [: 1H NMR (CDCL3) No. 9.91 (S, ] 1H), 8.25 (s, 1H), 8.17 (s, 1H), 7.83 (dd, J= 8.5, 1.5, 1H), 7.60 (d, J= 8.5, 1H).

8
[ 68-12-2 ]
[ 253801-04-6 ]

Yield	Reaction Conditions	Operation in experiment
52%		Example 1; Synthesis of 4-(lH-indazol-5-yl)-6-(4-phenoxyphenyl)pwimidin-2(lH)-one; STEP 1:; [0198] lH-indazole-5-carbaldehyde (2). w-Butyllithium (35.0 mL, 87.5 mmol) was added slowly to 5-bromoindazole (1, 4.98 g, 25.3 mmol) in THF (60 mL) at -780C. After 30 min, the solution was warmed to -4O0C over 30 min and then cooled to -780C. DMF (3.1 mL, 77.5 mmol) was added. After 15 min, the reaction flask was removed from the dry ice/acetone bath and stirred at room temperature for 2.5 h. The solution was quenched with H2O. The aqueous layer was extracted with EtOAc. The organic layer was washed with H2O and brine, dried over Na2SO4, filtered and concentrated to a golden oil. The crude material was purified by column chromatography (0-100% EtOAc/hexanes) to give 2 as a light yellow solid (1.91 g, 52% yield). LCMS m/z 147.0 (MH+), R, 1.53 min.[0199] Reference for the synthesis of lH-indazole-5-carbaldehyde: E. Piatnitski, WO 2005/000813 p 37.

Reference： [1]Patent: WO2007/124288,2007,A1 .Location in patent: Page/Page column 50

9
[ 253801-04-6 ]
[ 106-65-0 ]
C₁₃H₁₂N₂O₄ [ No CAS ]
C₁₃H₁₂N₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium tert-butylate; In tert-butyl alcohol; at 60℃; for 2h;	Intermediate Product 2: methyl 2-[1-(1H-indazol-5-yl)-methylidene]-succinate; 3.40 g (29.69 mmol) potassium-tert-butoxide was added to a solution of 2.00 g (13.68 mmol) 1H-indazol-5-carbaldehyde and 2.80 mL (20.97 mmol) dimethyl succinate in 100 mL tert-butanol and the mixture was stirred for 2 h at 60 C. The reaction mixture was cooled to RT, diluted with 200 mL water and the aqueous phase was washed twice with EtOAc. The aqueous phase was acidified with semiconc. aqueous HCl to pH 3-4 and exhaustively extracted with EtOAc. The combined org. phases were dried over magnesium sulphate, filtered through activated charcoal and evaporated down i. vac. The crude product was triturated with diisopropylether and a little isopropanol, filtered off and the residue was washed with diisopropylether (3.60 g, 1st stereoisomer). The mother liquor was evaporated down i. vac. and the residue was purified by column chromatography (silica gel, EtOAc/HOAc 10/0.1 v/v) and dried i. vac. (3.60 g, 2nd stereoisomer). Yield: 7.20 g (2 stereoisomers, 74% of theory) Rf=0.49 (silica gel, EtOAc/HOAc 100/1 v/v) ESI-MS: (M+H)+=261

Reference： [1]Patent: US2005/227968,2005,A1 .Location in patent: Page/Page column 16

10
[ 253801-04-6 ]
[ 106-65-0 ]
[ 635713-14-3 ]

Reference： [1]Patent: WO2005/84672,2005,A1 .Location in patent: Page/Page column 41
[2]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 2912 - 2916

11
[ 253801-04-6 ]
[ 100-58-3 ]
[ 1025762-64-4 ]

Yield	Reaction Conditions	Operation in experiment
64%		(b) To a solution of lH-<strong>[253801-04-6]indazole-5-carboxaldehyde</strong> (28 g, 200 mmol) and TMEDA (2m mL) in 1 L of THF was added a solution of 1.0M phenylmagnesium bromide in THF (800 mmol) dropwise. After 3 days, the reaction was quenched with sat. NaCl and extracted with 3 x EtOAc. The EtOAc extracts were dried over MgSO4, filtered, concentrated by rotary evaporator, and crystallized from CH2Cl2/ether to give 28.8 g (64%) of lH-indazol-5-yl)(phenyl)methanol. MS found: (M+H)+ = 225.
64%		(b) lH-Indazole-5-carbaldehyde (28 g, 200 mmol) was dissolved in 1 L of THF and 25 mL of TMEDA and treated with PhMgBr (800 mL of 1.0 M in THF, 800 mmol). After 36 h, the reaction was quenched with MeOH, poured into brine and extracted with EtOAc x 3. The organic layers were dried over MgSO4, filtered, and concentrated. Crude residue was crystallized from DCM/ether and solids were collected and dried to give 28.8 g (64%) of product lH-indazol-5- yl)(phenyl)methanol. MS found: (M+eta)+ = 319.

Reference： [1]Patent: WO2008/57856,2008,A2 .Location in patent: Page/Page column 80
[2]Patent: WO2008/57857,2008,A1 .Location in patent: Page/Page column 103

12
5-hydroxymethyl-1H-indazole [ No CAS ]
[ 253801-04-6 ]

Yield	Reaction Conditions	Operation in experiment
100%	With Dess-Martin periodane; In dichloromethane; for 12h;	(a) (lH-Indazol-5-yl)methanol (29 g, 200 mmol) was dissolved in 2 L DCM and treated with commercially available Dess-Martin periodinane (100 g, 235 mmol). After 12 h, the reaction mixture was concentrated in vacuo then dissolved in IL of EtOAc and washed with IN NaOH x 2. The organic layers were dried over MgSO4, filtered, and concentrated to give 28.6 g (100%) of product lH-indazole-5- carbaldehyde. MS found: (M+H)+ = 147.
82%	With Dess-Martin periodane; In dichloromethane;	EXAMPLE 29; 3-(lH-Indazol-5-yl)-2,2-dimethyl-3-phenyl-N-(thiazol-2-yl)propanamide; [00235] The procedure of Scheme B was used in preparing the Example 29 compound.; (a) (lH-Indazol-5-yl)methanol (17.3 g, 117 mmol) from experimental (Ic) was dissolved in 1 L dry DCM and Dess-Martin periodinane (53 g, 125 mmol) was added portionwise and the reaction was stirred overnight. The next day, the reaction was extracted with 1 M NaOH x 3. The aqueous layers were pooled and extracted with EtOAc x 5. The combined organic layers were dried over MgSO4, filtered, concentrated in vacuo to give 14. Ig (82% yield) of yellow solid leta-indazole-5- carbaldehyde. MS found: (M+H)+ = 147.
74%	With Dess-Martin periodane; In dichloromethane; at 20℃; for 0.5h;	The above product (125 mg, 0.844 mmol) was dissolved in 6.8 mL of dry dichloromethane, and Dess-Martin periodinane (376 mg, 0.887 mmol) was added to the solution at room temperature. After the reaction mixture was stirred for 30 min, saturated NaHCO3 aqueous solution was added. The mixture was extracted with chloroform, and the extract was washed with brine, and dried over MgSO4. After filtration, the filtrate was concentrated in vacuo, and the residue was purified by silica gel column chromatography (chloroform/methanol = 98/2 to 90/10) to obtain the title compound as a pale yellow solid (111 mg, 74%).

With 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione; In ethyl acetate; at 90℃; for 17h;

Reference Example 9 1H-indazole-5-carboaldehyde To an ethyl acetate solution (600 mL) of (1H-indazol-5-yl)methanol (6.00 g) obtained in Reference Example 8, IBX (11.9 g, Synthetic Product 2) was added. The resultant mixture was stirred for 17 hours at 90 C. After the stirring was ended, the mixture was filtered, and the filtered solution was distilled away under a reduced pressure. Subsequently, a column chromatography (as an elution solution, 100:0 to 94:6 (v/v) of chloroform/methanol was used) using silica gel 60N was performed, so that 5.74 g of the titled compound was obtained. "Synthetic Product 2" was synthesised based on a method disclosed in the document of J. Org. Chem. vol. 64, p. 4537 (1999).

Reference： [1]Patent: WO2008/57857,2008,A1 .Location in patent: Page/Page column 103
[2]Patent: WO2008/57856,2008,A2 .Location in patent: Page/Page column 80
[3]Patent: EP2123637,2009,A1 .Location in patent: Page/Page column 66
[4]Patent: US2008/200535,2008,A1 .Location in patent: Page/Page column 134
[5]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 5442 - 5447

13
[ 201230-82-2 ]
[ 55919-82-9 ]
[ 141-53-7 ]
[ 253801-04-6 ]

Yield	Reaction Conditions	Operation in experiment
59%	bis-triphenylphosphine-palladium(II) chloride; In N,N-dimethyl-formamide; at 110℃; for 6h;	A mixture of 5-iodoindazole (10 g, 41 mmol) , HCOONa (5.57 g, 82 mmol) and PdCI2(PPh3J2 (1.44 g, 2.05 mmol) in DMF (60 mL) was put under vacuum and charged with carbon monoxide (CO). This process was repeated three times, after which the mixture was kept at 110 0C for 6 hr. After cooling to room temperature (rt), the reaction mixture was diluted with brine and extracted with EtOAc. The organic phases were combined, washed with brine, dried, and concentrated. The crude product was purified by column chromatography to afford 1 H-indazole-5-carboxaldehyde (3.52 g, 59%) as a white solid.

Reference： [1]Patent: WO2008/71451,2008,A1 .Location in patent: Page/Page column 47

14
[ 253801-04-6 ]
[ 1118-61-2 ]
[ 1033767-84-8 ]

Yield	Reaction Conditions	Operation in experiment
44%		A mixture of 1 H-<strong>[253801-04-6]indazole-5-carboxaldehyde</strong> from Synthetic Preparation 1 (447 mg, 3.1 mmol) and 3-aminocrotononitrile (526.4 mg, 6.41 mmol) in HOAc (10 mL) was kept at 1 10 0C for 1.5 hr, after which it was cooled to rt. The reaction was treated with NaHCO3 (sat.) to pH 10, and extracted with EtOAc. The organic phases were combined, washed with brine, and dried. Concentration followed by purification with flash chromatography afforded 1 ,4-dihydro-4-(1 H-indazol-5-yl)-2,6-dimethyl-3,5-pyridinedicarbonitrile (370 mg, 44%) (Cpd. No. 80, Table 2). 1 H-NMR (400 MHz, CDCI3): delta = 8.07 (s, 1 H), 7.64 (s, 1 H), 7.53 (d, 1 H)1 7.35 (d, 1 H), 4.48 (s, 1 H), 2.03 (s, 6H) ppm.

Reference： [1]Patent: WO2008/71451,2008,A1 .Location in patent: Page/Page column 59

15
[ 253801-04-6 ]
[ 314267-78-2 ]
[ 1118-61-2 ]
1,4-dihydro-2-(4-chloropyrid-3-yl)-6-methyl-4-(1H-indazol-5-yl)-3,5-pyridinedicarbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39.3%		SYNTHETIC EXAMPLE 6A mixture of theta-chloro^'-oxo-S-pyridinepropanenitrile (1.2 g, 6.64 mmol), from Synthetic Preparation 4, and 1 H-<strong>[253801-04-6]indazole-5-carboxaldehyde</strong> (0.81 g, 5.54 mmol) was kept at reflux in EtOH (50 ml.) for 15 min, and 3-aminocrotononitrile (475 mg, 5.79 mmol) was added. The reaction mixture was kept at reflux for 2 hr, then HOAc was added. The reaction mixture was heated to reflux for 1.5 hr, and cooled to rt. All solvents were removed under vacuum, and the crude product was purified by column to afford 1 ,4-dihydro-2-(4- chloropyrid-3-yl)-6-methyl-4-(1 H-indazol-5-yl)-3F5-pyridinedicarbonitrile (974 mg, 39.3%) (Cpd. No. 270, Table 5). 1 H-NMR (400 MHz1 DMSO-D6): delta = 13.10 (s, 1 H)1 9.70 (s, 1H)1 8.32 (S, 1H), 8.10 (S1 1H)1 7.75 (m, 2H), 7.60 (m, 1H), 7.39 (m ,1H)1 6.95 (m, 1H), 4.64 (s, 1 H), 3.70 (m, 4H), 3.55 (m, 4H), 2.13 (s, 3H) ppm.

Reference： [1]Patent: WO2008/71451,2008,A1 .Location in patent: Page/Page column 60

16
[ 253801-04-6 ]
[ 944899-01-8 ]

Yield	Reaction Conditions	Operation in experiment
72%	With iodine; sodium hydroxide; In 1,4-dioxane; water; at 20℃; for 2h;	Example 4A3 -Iodo- 1 H-indazole-5 -carbaldehyde 20 g (137 mmol) lH-indazole-5-carbaldehyde [preparation described in US 2005/0227968-A1 (Intermediate I)], dissolved in 1,4-dioxane (640 ml), were treated with a solution of sodium hydroxide (82 g, 2053 mmol) in water (640 ml). Then, 43.2 g (170 mmol) iodine were added, and the mixture was stirred at room temperature for 1 h. Subsequently, a second batch of 43.2 g (170 mmol) iodine was added, and the mixture was again stirred at room temperature for 1 h. The mixture was concentrated under reduced pressure yielding a solid precipitate. After filtration, the precipitate was washed with water and dried under high vacuum over phosphorous oxide in a desiccator for 12 h affording the title compound (26.6 g, 72% of th.) as a pale yellow solid.1H-NMR (400 MHz, DMSOd6): ? = 9.81 (s, IH), 7.74 (d, IH), 7.40 (d, IH), 7.32 (dd, IH) ppm.
72%	With iodine; sodium hydroxide; In 1,4-dioxane; water; at 20℃; for 2h;	Example 3A3-Iodo-lH-indazole-5-carbaldehyde20 g (137 mmol) lH-indazole-5-carbaldehyde [preparation described in US 2005/0227968-A1 (Intermediate I)], dissolved in 1,4-dioxane (640 ml), were treated with a solution of sodium hydroxide (82 g, 2053 mmol) in water (640 ml). Then, 43.2 g (170 mmol) iodine were added, and the mixture was stirred at room temperature for 1 h. Subsequently, a second batch of 43.2 g (170 mmol) iodine was added, and the mixture was again stirred at room temperature for 1 h. The mixture was concentrated under reduced pressure yielding a solid precipitate. After filtration, the precipitate was washed with water and dried under high vacuum over phosphorous oxide in a desiccator for 12 h affording the title compound (26.6 g, 72% of th.) as a pale yellow solid.1H-NMR (400 MHz, DMSOd6): delta = 9.81 (s, IH), 7.74 (d, I H), 7.40 (d, IH), 7.32 (dd, IH) ppm.
64.5%	With sodium hydroxide; iodine; In 1,4-dioxane; water; at 20℃; for 2h;	SYNTHETIC PREPARATION 2To a solution of 1 H-<strong>[253801-04-6]indazole-5-carboxaldehyde</strong> (3.75 g, 25.7 mmol) in dioxane (120 mL) was added a solution of NaOH (15.48 g, 384.9 mmol) in water (120 ml_). To this solution, iodine (8.2 g, 32 mmol) was added. After 1 hr at rt, more iodine (8.2 g, 32 mmol) was added, and the reaction mixture was stirred for an additional 1 hr at rt. After removal of most of the dioxane in vacuo, the reaction mixture was extracted with EtOAc, washed with brine, dried, and concentrated. The crude product was purified by flash chromatography to afford 3-iodo-1 H-<strong>[253801-04-6]indazole-5-carboxaldehyde</strong> (4.5 g, 64.5%).

48%	With iodine; potassium carbonate; In N,N-dimethyl-formamide; for 3h;	To a solution of 1 H-indazole-5-carbaldehyde (315.2 mg, 2.16 mmol), K2CO3 (598.8 mg, 4.33 mmol) in DMF (2.5 mL) was added dropwise a solution of I2 (938 mg, 3.7 mmol) in DMF (2.5 mL) and the reaction allowed to stir for three hours. An aqueous solution consisting OfNa2S2O4 (511 mg) / K2CO3 (35 mg) / H2O (3.5 mL) was then added and the solution stirred for two hours. Water (3OmL) and aqueous sodium hydrogen sulfate (IM, 1OmL) was added and the product was extracted with ethyl acetate (350 mL); this organic layer was washed with brine (3x25mL). The aqueous layer was then extracted with dichloromethane (3x75mL), this second organic layer was also washed with brine (25mL). TLC indicated product present in both, so the residues were combined and purified by chromatography (1Og silica SPE tube, Silicycle, 5% ethyl acetate in dichloromethane) to yield a beige solid (203mg, 35%). A precipitate that formed in the original aqueous layer was collected by vacuum filtration to give after drying a beige solid (first crop 135.6 mg, 23 %; second crop 147 mg, 25%). 1H NMR (400 MHz, CDCl3 plus a drop of CD3OD) delta 10.03 (s, IH), 8.00 (s, IH), 7.95 (d, J= 8.8 Hz, IH), 7.54 (d, J= 8.8 Hz, IH).
48%	With iodine; potassium carbonate; In N,N-dimethyl-formamide; for 3h;	A. 3-Iodo-lH-indazole-5-carbaldehydeTo a solution of lH-indazole-5-carbaldehyde (315.2 mg, 2.16 mmol), K2C03 (598.8 mg, 4.33 mmol) in DMF (2.5 mL) was added dropwise a solution of I2 (938 mg, 3.7 mmol) in DMF (2.5 mL) and the reaction allowed to stir for three h. An aqueous solution consisting of Na2S204 (51 1 mg) / K2C03 (35 mg) / H20 (3.5 mL) was then added and the solution stirred for 2 h. Water (30 mL) and aqueous sodium hydrogen sulfate (1M, 10 mL) was added and the product was extracted with ethyl acetate (350 mL); this organic layer was washed with brine (3x 25 mL). The aqueous layer was then extracted with dichloromethane (3x 75 mL), this second organic layer was also washed with brine (25 mL). TLC indicated product present in both, so the residues were combined and purified by chromatography (lOg silica SPE tube, Silicycle, 5% ethyl acetate in dichloromethane) to yield a beige solid (203 mg, 35%). A precipitate that formed in the original aqueous layer was collected by vacuum filtration to give after drying a beige solid (first crop 135.6 mg, 23%; second crop 147 mg, 25%). NMR (400 MHz, CDCl} plus a drop of CD3OD) delta 10.03 (s, 1H), 8.00 (s, 1H), 7.95 (d, J =8.8 Hz, 1H), 7.54 (d, J =8.8 Hz, 1H).
	With iodine; potassium hydroxide; In N,N-dimethyl-formamide; at 20℃; for 4h;	To a solution of <strong>[253801-04-6]1H-<strong>[253801-04-6]indazole-5-carboxaldehyde</strong></strong> (670.2 mg, 4.59 mmol) in DMF (5 mL) were added iodine (2.33 g, 9.17 mmol) and potassium hydroxide pellets (1.03 g, 18.36 mmol) at room temperature under stirring. After 4 h, the mixture was quenched with aqueous Na2S2O3 solution and extracted with EtOAc. The combined extracts were washed with brine, dried, and evaporated to afford the title product.1H NMR (400 MHz, CD3OD) delta10.05 (s, 1H), 8.10 (m, 1H), 7.99 (dd, 1H), 7.65 (d, 1H).LC/MS (m/z) [M+1]+ 272.9 (calculated for C8H51N2O, 271.94).

Reference： [1]Patent: WO2009/149837,2009,A1 .Location in patent: Page/Page column 55
[2]Patent: WO2011/3604,2011,A1 .Location in patent: Page/Page column 39
[3]Patent: WO2008/71451,2008,A1 .Location in patent: Page/Page column 48
[4]Patent: WO2009/79767,2009,A1 .Location in patent: Page/Page column 192
[5]Patent: WO2011/123937,2011,A1 .Location in patent: Page/Page column 67
[6]Patent: US2011/150864,2011,A1 .Location in patent: Page/Page column 210-211
[7]Journal of the American Chemical Society,2013,vol. 135,p. 5298 - 5301

17
[ 253801-04-6 ]
[ 109-77-3 ]
C₁₁H₈N₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With piperidine; In ethanol; at 20℃; for 2h;	SYNTHETIC EXAMPLE 13To a mixture of 1 H-<strong>[253801-04-6]indazole-5-carboxaldehyde</strong> (200 mg, 1.37 mmol), from Synthetic Preparation 1 , and malononitrile (100 mg, 1.51 mmol) in EtOH (5 mL) was added piperidine (0.2 mL). The mixture was stirred at rt for 2 hr, after which the solid (140 mg) was collected by filtration. This solid and 2-piperidinylidene-ethanenitrile (100 mg, 0.82 mmol; per Synthetic Preparation 5) were combined in EtOH (5 mL). The resulting mixture was kept at 90 0C for 1 hr. After cooling to rt, the solvent was removed in vacuo. The residue was purified on flash column (silica gel) and crystallized further in acetate to afford 4-amino-6,7,8,9-tetrahydro-2- (1 H-indazol-5-yl)- 2H-quinolizine-1 ,3-dicarbonitrile (110 mg, 25.4%) (Cpd. No. 305). 1 H-NMR (400 MHz, CD3OD): delta = 8.02 (s, 1 H), 7.58 (s, 1 H), 7.53 (d, 1 H), 7.34 (d, 1 H), 4.53 (s, 1 H), 3.63 (d, 2H), 2.72 (m, 2H), 1.95 (m, 1 H), 1.73-1.88 (m, 3H) ppm.

Reference： [1]Patent: WO2008/71451,2008,A1 .Location in patent: Page/Page column 64

18
[ 253801-04-6 ]
[ 25560-26-3 ]
C₁₅H₁₆N₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol; at 90℃;	SYNTHETIC EXAMPLE 12<strong>[253801-04-6]1H-<strong>[253801-04-6]indazole-5-carboxaldehyde</strong></strong> (146 mg, 1 mmol), from Synthetic Preparation 1, and 2-piperidinylidene-ethanenitrile (122 mg, 1 mmol), from Synthetic Preparation 5, were mixed in 5 mL EtOH. The mixture was heated at 90 0C overnight. After removal of solvent in vacuo, the residue was dissolved in 5 mL acetic acid, and 3-aminocrotononitrile (82 mg, 1 mmol) was added. The mixture was heated at 115 0C for 10 min. After cooling, the acetic acid was removed in vacuo. The resulting residue was dissolved in 20 mL acetate, washed with 10 mL1 M K2CO3, dried, and concentrated in vacuo. The crude mixture was purified on flash column (silica gel) to afford a mixture (52 mg), which was further purified on HPLC. The fractions were collected and were neutralized with 2N Na2CO3 to pH 11. <n="65"/>This mixture was extracted with 40 mL ethyl acetate, dried, and concentrated. The product was re-dissolved in 2 mL CH3CN and 2 mL water, and dried under vacuum to afford 6,7,8,9- tetrahydro-2-(1H-indazol-5-yl)-4-methyl-2H-quinolizine-1 ,3-dicarbonitrile (40 mg, 13%) (Cpd. No. 304). 1 H-NMR (400 MHz, DMSO-D6): delta = 8.08 (s, 1 H), 7.61 (s, 1 H), 7.56 (d, 1 H), 7.30 (d, 1H), 4.46 (s, 1 H), 3.60 (d, 2H), 2.63 (m, 2H), 2.22 (s, 3H), 1.80 (m, 2H), 1.65 (m, 2H) ppm.

Reference： [1]Patent: WO2008/71451,2008,A1 .Location in patent: Page/Page column 63-64

19
[ 253801-04-6 ]
[ 100-39-0 ]
[ 1008769-33-2 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 5h;	Reference Example 10 1-benzyl-1H-indazole-5-carboaldehyde To an N,N-dimethyl formamide solution (3.0 mL) of 1H-indazole-5-carboaldehyde (200 mg) obtained in Reference Example 9, potassium carbonate (379.0 mg) and benzylbromide (325 muL, manufactured by Wako Pure Chemical Industries, Ltd.) were added. The resultant mixture was stirred for 5 hours at room temperature. After the stirring was ended, a saturated ammonium chloride aqueous solution (10 mL) was poured into the reaction mixture solution, and extraction was performed by using ethyl acetate (20 mL*2). An organic layer was washed with a saline solution and dried, and the solvent was distilled away under a reduced pressure. Subsequently, chromatography (as an elution solution, 3:1 (v/v) of hexane/ethyl acetate was used) using Biotage 12M cartridge was performed, so that 204.9 mg of the titled compound was obtained. ESI-MS: 237 (M+H), RTime 4.48 min.

Reference： [1]Patent: US2008/200535,2008,A1 .Location in patent: Page/Page column 134

20
[ 53857-57-1 ]
[ 68-12-2 ]
[ 253801-04-6 ]

Yield	Reaction Conditions	Operation in experiment
51%		A) Preparation of Intermediate Products; Intermediate Product 1: 1H-indazole-5-carbaldehyde; 2.60 g (65.00 mmol) sodium hydride (60% in mineral oil) was added batchwise to a solution of 11.64 g (59.08 mmol) 5-bromo-1H-indazole in 150 mL THF under argon within 10 minutes and the mixture was stirred for 15 minutes at RT. The reaction mixture was cooled to -70 C. and within 30 minutes 100.00 mL (130.00 mmol) sec-butyllithium (1.3 M in cyclohexane) were added dropwise, while the temperature was kept below -60 C. The mixture was stirred for a further 2 h at -70 C. and then a solution of 20.00 mL (0.260 mol) DMF in 20 mL THF was added dropwise, while the temperature was kept below -50 C. The reaction mixture was slowly heated to RT and stirred for 16 h. Then the mixture was slowly cooled to 0 C. and slowly 180 mL of 2N aqueous HCl was added dropwise, the mixture was stirred for a further 15 minutes and the pH was adjusted to 9-10 with sat. aqueous sodium bicarbonate solution. The aqueous phase was exhaustively extracted with EtOAc, the combined org. phases were dried over magnesium sulphate and evaporated down i. vac. Column chromatography (silica gel, petroleum ether/EtOAc 1:1 v/v), trituration with hexane and drying i. vac. at 50 C. yielded the product. Yield: 4.40 g (51% of theory) Rf=0.37 (silica gel, petroleum ether/EtOAc 1/1 v/v) ESI-MS: (M+H)+=147
	With n-butyllithium; In tetrahydrofuran; hexane; at -50 - 20℃;	To a solution of 5-bromoindazole (5 g, 25.38 mmol) in tetrahydrofuran (100 mL) cooled at -500C under argon was added dropwise a solution of 1.6 M n-butyllithium in hexanes (40 mL, 63.44 mmol). Dimethylformamide (3.9 mL, 50.75 mmol) was added, and the mixture was allowed to warm to room temperature and stirred for 15 minutes. The mixture was then quenched with water, extracted with ethyl acetate, preabsorbed onto silica gel and purified by silica gel chromatography eluting with a gradient of 10-30% ethyl acetate in hexanes to afford the title compound. 1H NMR (500 MHz, DMSO-d<j) delta ppm 10.03 (s, 1 H) 8.45 (s, 1 H) 8.35 (s, 1 H) 7.85 (dd, J=8.70, 1.37 Hz, 1 H) 7.69 (d, J=8.54 Hz, 1 H)

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 4482 - 4485
[2]Patent: WO2005/84672,2005,A1 .Location in patent: Page/Page column 40-41
[3]Patent: US2005/227968,2005,A1 .Location in patent: Page/Page column 15-16
[4]Patent: WO2008/154241,2008,A1 .Location in patent: Page/Page column 67

21
[ 253801-04-6 ]
[ 100-46-9 ]
[ 76-05-1 ]
[ 165806-95-1 ]
5-[1-benzyl-4-(4-fluorophenyl)-1H-imidazol-5-yl]-1H-indazole trifluoroacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Into a 20 mL scintillation vial was added 50.0 mg (0.34 mmol) of Example 36A. To the solid was added a 2.0 mL dimethylformamide solution containing 0.46 mmol (49 mg) of benzylamine and 50 mg of powdered activated 4A molecular sieves. The vial was then capped and heated at 60 0C for 4 hours on an orbital shaker. The vial was allowed to cool to ambient temperature; and was uncapped. To the suspension was added 32 mg (0.23 mmol) of anhydrous potassium carbonate followed by 66 mg (0.23 mmol) alpha-(p-toluenesulfonyl)-4- fluorobenzylisonitrile. The vial was then capped and heated overnight at 60 0C on a shaker. The vial was removed from the shaker; allowed to cool to ambient temperature; and the resulting suspension was filtered. The filtrate was evaporated under reduced pressure at medium heat on a Savant Speed Vac. The crude residues were redissolved in 1 : 1DMSO/methanol and purified by reverse-phase HPLC using an acetonitrile/water TFA gradient elution method to afford the title compound as the TFA salt. 1H NMR (300 MHz, DMSO-d6) delta ppm 9.01 (s, 1 H) 8.12 (s, 1 H) 7.76 (s, 1 H) 7.60 (d, J=8.48 Hz, 2 H) 7.32 - 7.45 <n="70"/>(m, 2 H) 7.09 - 7.30 (m, 6 H) 6.96 (d, J=6.61, 2.88 Hz, 2 H) 5.23 (s, 2 H). MS (DCI) m/z 369 (M+H)+.

Reference： [1]Patent: WO2008/154241,2008,A1 .Location in patent: Page/Page column 68

22
[ 253801-04-6 ]
[ 96-50-4 ]
[ 931-53-3 ]
[ 76-05-1 ]
N-cyclohexyl-6-(1H-indazol-5-yl)imidazo[2,1-b][1,3]thiazol-5-amine trifluoroacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		N-cyclohexyl-6-(lH-indazol-5-yl)imidazo[2,l-b][l,3]thiazol-5-amine Example 36A (50 mg, 0.34 mmol) and 2-aminothiazole (28 mg, 0.34 mmol) were combined with scandium triflate (8 mg, 0.017 mmol) in anhydrous methanol (1 mL) in a 4 mL vial. The vial was sealed and shaken at ambient temperature for 30 minutes. Cyclohexyl isocyanide (42 mL, 0.34 mmol) was added, and the mixture was shaken for 2 days at room temperature. The mixture was purified by reverse-phase HPLC using an acetonitrile/water 0.1% TFA gradient elution method to afford the title compound as the TFA salt. 1H NMR (500 MHz, DMSO-d6) delta ppm 13.12 (s, 1 H) 8.32 (s, I H) 8.13 (s, 1 H) 8.05 (d, J=8.85, 1.22 Hz, 1 H) 7.92 (d, J=4.27 Hz, 1 H) 7.60 (d, J=8.54 Hz, 1 H) 7.37 (d, J=3.66 Hz, 1 H) 4.89 (s, 1 H) 2.78 - 2.94 (m, 1 H) 1.73 - 1.83 (m, 2 H) 1.58 - 1.68 (m, 2 H) 1.45 - 1.53 (m, 1 H) 1.16 - 1.29 (m, 2 H) 1.04 - 1.14 (m, 3 H). MS (ESI+) m/z 338.1 (M+H)+.

Reference： [1]Patent: WO2008/154241,2008,A1 .Location in patent: Page/Page column 67

23
[ 253801-04-6 ]
[ 109-12-6 ]
[ 598-45-8 ]
[ 1093302-84-1 ]

Yield	Reaction Conditions	Operation in experiment
		Example 36A (42 mg, 0.287 mmol) and 2-aminopyrimidine (27 mg, 0.284 mmol) were combined with scandium trifiate (7 mg, 0.014 mmol) in anhydrous methanol (2 mL) in <n="71"/>a 4 mL vial. The vial was sealed and shaken at ambient temperature for 30 minutes. Isopropyl isocyanide (27 mL, 0.286 mmol) was added and the mixture was shaken at ambient temperature overnight, followed by 400C for 2 hours. The mixture was absorbed on silica gel and purified using silica gel chromatography eluting using a gradient of 0-5% methanol in dichloromethane to afford the title compound. 1H NMR (300 MHz, DMSOd5) delta ppm 13.08 (s, 1 H) 8.75 (d, J=6.95, 1.86 Hz, 1 H) 8.60 (s, 1 H) 8.31 (d, J=8.82, 1.36 Hz, 1 H) 8.20 (d, J=4.75 Hz, 1 H) 8.14 (s, 1 H) 7.60 (d, J=8.82 Hz, 1 H) 7.03 (d, J=6.78, 4.07 Hz, 1 H) 6.54 (d, J=4.75 Hz, 1 H) 4.86 (d, J=5.09 Hz, 1 H) 1.05 (d, J=6.10 Hz, 6 H). MS (ESI+) m/z 293.0 (M+H)+.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 1480 - 1483
[2]Patent: WO2008/154241,2008,A1 .Location in patent: Page/Page column 69-70

24
[ 253801-04-6 ]
[ 106018-85-3 ]
[ 635713-79-0 ]

Reference： [1]Journal of Organic Chemistry,2008,vol. 73,p. 8502 - 8510

25
[ 253801-04-6 ]
[ 1056249-39-8 ]
C₂₅H₂₁N₅O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 4344 - 4347

26
[ 253801-04-6 ]
(2-amino-phenyl)-(1H-indol-3-yl)-methanone [ No CAS ]
C₂₃H₁₆N₄O [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 4344 - 4347

27
[ 253801-04-6 ]
[ 1056249-32-1 ]
C₂₂H₁₅N₅O [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 4344 - 4347

28
[ 253801-04-6 ]
[ 57-13-6 ]
C₉H₈N₄O [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 4482 - 4485

29
[ 253801-04-6 ]
[ 99-02-5 ]
[ 1061620-49-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 4482 - 4485

30
[ 253801-04-6 ]
[ 59-48-3 ]
[ 1168720-74-8 ]

Yield	Reaction Conditions	Operation in experiment
7.6%	With piperidine; In ethanol; at 90℃; for 2h;	A scintillation vial was charged with indolin-2-one (67 mg, 0.500 mmol), lH-indazole-5-carbaldehyde (73 mg, 0.550 mmol), piperidine (5.0 uL, 0.076 mmol) and EtOH (2 mL). The reaction was then heated to 9O0C for 2 hrs. The EtOH was removed and the product purified by preparatory reverse-phase HPLC to give 10 mg, 7.6 % of the title compound. 1H NMR (400 MHz, CD3OD) delta 8.20-8.18 (m, 2H), 7.89 (s, IH), 7.76 (d, J = 7.9 Hz, IH), 7.71-7.67 (m, 2H), 7.24 (t, J = 7.4 Hz, IH), <n="101"/>6.93 (d, J = 7.7 Hz, IH), 6.90 (t, J = 7.5 Hz, IH); MS ESI 262.0 [M + H]+, calcd for [C16HnN3O + H]+ 262.10.

Reference： [1]Patent: WO2009/79767,2009,A1 .Location in patent: Page/Page column 99

31
[ 253801-04-6 ]
[ 1086391-08-3 ]

Yield	Reaction Conditions	Operation in experiment
75%	With N-Bromosuccinimide; In acetonitrile; at 20℃; for 0.833333h;Reflux;	Example IQAS-Bromo-lH-indazole-S-carbaldehyde To a solution of 20 g (137 mmol) lH-indazole-5-carbaldehyde in acetonitrile (580 ml), 28 g (157 mmol) l-bromopyrrolidine-2,5-dione were added over 20 min at room temperature. The resul- ting suspension was stirred under reflux for 30 min, then cooled to room temperature and concentrated under reduced pressure. The residue was dissolved in ethyl acetate (1500 ml), and the solution was washed with water and with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was triturated with ethyl acetate. After filtration, the precipitate was dried under vacuum to yield the title compound as a white solid (30.9 g, 75% of th.).LC-MS (method 4): R, = 0.77 min; MS (ESIpos): m/z = 225 (M+?)+1H-NMR (400 MHz, DMSOd6): ? = 15.01 (br. s, IH), 10.09 (s, IH), 8.29 (s, IH), 7.91 (d, IH), 7.73 (d, IH) ppm.
70.9%	With N-Bromosuccinimide; at 0 - 20℃;	To a solution of <strong>[253801-04-6]1H-indazole-5-carbaldehyde</strong> (1 g, 6.85 mmol) in toluene (15 mL) was added NBS (1.46 g, 8.22 mmol) at 0 C. After the reaction was stirred at room temperature overnight, the reaction mixture was cooled to 0 C. The solid precipitated was collected by filtration, washed with MeCN and water, and dried to afford compound S2 (1.3 g, 70.9% yield) as a white solid. LC/MS (ESI) m/z: 224 (M+H)+.

Reference： [1]Organic Process Research and Development,2014,vol. 18,p. 321 - 330
[2]Patent: WO2009/149836,2009,A1 .Location in patent: Page/Page column 50
[3]Patent: WO2017/35353,2017,A1 .Location in patent: Paragraph 1409

32
[ 253801-04-6 ]
[ 1086391-03-8 ]

Yield	Reaction Conditions	Operation in experiment
97%	With N-chloro-succinimide; In acetonitrile; at 20℃; for 12h;Reflux;	Example 43A3 -Chloro- 1 H-indazole-5 -carbaldehyde To a solution of 4.0 g (27.4 mmol) 1 H-indazole-5 -carbaldehyde [preparation described in US 2005/0227968-A1 (Intermediate I)] in acetonitrile (116 ml) were added 4.2 g (31.5 mmol) N- chlorosuccinimide at room temperature. The resulting solution was stirred under reflux for 12 h. The mixture was then concentrated under reduced pressure yielding a solid precipitate. This material was triturated with water, filtered, and dried under high vacuum for 12 h to give the title compound (4.8 g, 97% of th.) as a white solid. 1H-NMR (400 MHz, DMSO-Ci6): ? = 13.76 (s, IH), 10.06 (s, IH), 8.37 (s, IH), 7.92 (d, IH), 7.72 (d, IH) ppm.
54%	With N-chloro-succinimide; In acetonitrile; at 65 - 70℃; for 50h;	To a solution of 1H-Indazole-5-carbaldehyde (3.2 g, 21.89 mmol) in acetonitrile (140 mL) was added N-Chlorosuccinimide (3.5 g, 26.27 mmol). After stirring for 50 hours at 65 to 70 C., the precipitate was filtered, washed with cold acetonitrile, abundantly with water and dried to afford the title compound as a white solid (2.15 g, 54%).1H NMR (400 MHz, CDCl3) delta13.78 (s, 1H), 10.08 (s, 1H), 8.37 (d, 1H), 7.92 (dd, 1H), 7.72 (d, 1H).LC/MS (m/z) [M+1]+ 181.2 (calculated for C8H5ClN2O, 180.01).

Reference： [1]Patent: WO2009/149837,2009,A1 .Location in patent: Page/Page column 78-79
[2]Patent: US2011/150864,2011,A1 .Location in patent: Page/Page column 208

33
[ 253801-04-6 ]
[ 3859-41-4 ]
[ 1118-61-2 ]
[ 1240786-14-4 ]

Yield	Reaction Conditions	Operation in experiment
13%		Example 144-(lH-Indazol-5-yl)-2-methyl-5-oxo-4,5,6,7-tetrahydro-lH-cyclopenta[b]pyridine-3-carbonitrile100 mg (1.026 mmol) cyclopentane-l,3-dione, 150 mg (1.026 mmol) lH-indazole-5-carbaldehyde and piperidine (0.1 ml) in ethanol (8 ml) were heated to reflux for 4 h. The mixture was then evaporated to dryness, the remaining solid was dissolved in acetic acid (8 ml), and 84 mg(1.026 mmol) 3-aminobut-2-enenitrile were added. The solution was heated to reflux for 2 h. After cooling, the mixture was evaporated to dryness again, and the remaining solid was purified by preparative RP-EtaPLC (acetonitrile/water gradient) to yield 40 mg (13% of th.) of the title com- pound.LC-MS (method 5): R, = 1.27 min; MS (ESIpos): m/z = 291 (M+Eta)+ 1H-NMR (400 MHz, DMSO-d6): delta = 12.99 (s, IH), 10.08 (s, IH), 8.02 (s, IH), 7.52 (s, IH), 7.46 (d, IH), 7.22 (dd, IH), 4.49 (s, IH), 2.69-2.56 (m, 2H), 2.26-2.23 (m, 2H), 2.12 (s, 3H) ppm

Reference： [1]Patent: WO2010/94405,2010,A1 .Location in patent: Page/Page column 75

34
[ 253801-04-6 ]
[ 128-08-5 ]
[ 1086391-08-3 ]

Yield	Reaction Conditions	Operation in experiment
75%	In acetonitrile; at 20℃; for 0.833333h;Reflux;	Example 13A3 -Bromo- 1 H-indazole-5 -carbaldehydeTo a solution of 20 g (137 mmol) lH-indazole-5-carbaldehyde in acetonitrile (580 ml), 28 g (157 mmol) l-bromopyrrolidine-2,5-dione were added over 20 min at room temperature. The resulting suspension was stirred under reflux for 30 min, then cooled to room temperature and concentrated under reduced pressure. The residue was dissolved in ethyl acetate (1500 ml), and the solution was washed with water and with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was triturated with ethyl acetate. After filtration, the precipitate was dried under vacuum to yield the title compound as a white solid (30.9 g, 75% of th.).LC-MS (method 4): Rt = 0.77 min; MS (ESIpos): m/z = 225 (M+Eta)+ 1H-NMR (400 MHz, DMSOd6): delta = 15.01 (br. s, IH), 10.09 (s, IH), 8.29 (s, IH), 7.91 (d, IH), 7.73 (d, IH) ppm.

Reference： [1]Patent: WO2010/94405,2010,A1 .Location in patent: Page/Page column 62

35
[ 253801-04-6 ]
Sodium 1-cyanoprop-1-ene 2-oxide [ No CAS ]
[ 1240786-40-6 ]

Yield	Reaction Conditions	Operation in experiment
	With piperidine; acetic acid; In dichloromethane; for 7h;Reflux;	Example 8A(2£)-2-(lH-Indazol-5-yhnethylidene)-3-oxobutanenitrile10 g (68.4 mmol) lH-indazole-5-carbaldehyde [preparation described in US 2005/0227968-A1 (Intermediate I)], 7.91 g (75.2 mmol) sodium (lZ)-l-cyanoprop-l-en-2-olate, 4.89 ml (85.5 mmol) acetic acid and 0.68 ml (6.84 mmol) piperidine in dry dichloromethane (500 ml) were stirred at reflux temperature for 7 h using an inverse water separator. Upon cooling, a precipitate was formed which was collected by filtration and washed with dichloromethane. The solid was dried in vacuo to afford the crude title compound (19 g, 75% purity by LC-MS, 96% of th.) which was used in subsequent steps without further purification.LC-MS (method 2): R, = 0.82 min; MS (ESIpos): m/z = 212 (M+Eta)+.
	With acetic acid;piperidine; In dichloromethane; for 7h;Molecular sieve; Reflux;	10 g (68.4 mmol) lH-indazole-5-carbaldehyde [preparation described in US 2005/0227968-A1 (Intermediate 1)], 7.91 g (75.2 mmol) sodium (lZ)-l-cyanoprop-l-en-2-olate, 4.89 ml (85.5 mmol) acetic acid and 0.68 ml (6.84 mmol) piperidine in dry dichloromethane (500 ml) were stirred at reflux temperature for 7 h using an inverse water separator. Upon cooling, a precipitate was formed which was collected by filtration and washed with dichloromethane. The solid was dried in vacuo to afford the crude title compound (19 g, 75% purity by LC-MS, 96% of th.) which was used in subsequent steps without further purification.LC-MS (method 2): Rt = 0.82 min; MS (ESIpos): m/z = 212 (M+H)+.
	With acetic acid;piperidine; In dichloromethane; for 7h;Reflux;	10 g (68.4 mmol) lH-indazole-5-carbaldehyde [preparation described in US 2005/0227968-A1 (Intermediate 1)], 7.91 g (75.2 mmol) sodium (lZ)-l-cyanoprop-l-en-2-olate, 4.89 ml (85.5 mmol) acetic acid and 0.68 ml (6.84 mmol) piperidine in dry dichloromethane (500 ml) were stirred at reflux temperature for 7 h using an inverse water separator. Upon cooling, a precipitate was formed which was collected by filtration and washed with dichloromethane. The solid was dried in vacuo to afford the crude title compound (19 g, 75% purity by LC-MS, 96%> of th.) which was used in subsequent steps without further purification.LC-MS (method 2): Rt = 0.82 min; MS (ESIpos): m/z = 212 (M+H)+.

Reference： [1]Patent: WO2010/94405,2010,A1 .Location in patent: Page/Page column 59
[2]Patent: WO2011/42367,2011,A1 .Location in patent: Page/Page column 30; 31
[3]Patent: WO2011/42368,2011,A1 .Location in patent: Page/Page column 38; 39

36
[ 253801-04-6 ]
[ 1093303-37-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 1480 - 1483

37
[ 253801-04-6 ]
[ 2038-03-1 ]
C₁₄H₁₈N₄O [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 1480 - 1483

38
[ 253801-04-6 ]
[ 2038-03-1 ]
[ 1093303-42-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 1480 - 1483

39
[ 253801-04-6 ]
[ 123-00-2 ]
C₁₅H₂₀N₄O [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 1480 - 1483

40
[ 253801-04-6 ]
[ 123-00-2 ]
[ 1093303-38-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 1480 - 1483

41
[ 253801-04-6 ]
[ 96-50-4 ]
[ 931-53-3 ]
[ 1093302-73-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 1480 - 1483

42
[ 253801-04-6 ]
[ 504-29-0 ]
[ 931-53-3 ]
[ 1093302-75-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 1480 - 1483

43
[ 253801-04-6 ]
[ 109-12-6 ]
[ 931-53-3 ]
[ 1093302-81-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 1480 - 1483

44
[ 253801-04-6 ]
[ 109-12-6 ]
[ 2769-64-4 ]
[ 1093302-92-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 1480 - 1483

45
[ 253801-04-6 ]
[ 109-12-6 ]
[ 1885-81-0 ]
[ 1093302-93-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 1480 - 1483

46
[ 253801-04-6 ]
[ 5049-61-6 ]
[ 931-53-3 ]
[ 1093302-76-1 ]

Yield	Reaction Conditions	Operation in experiment
14.1%	With perchloric acid; In dimethyl sulfoxide; at 100℃; for 2h;	lH-indazole-5-carbaldehyde (58.7 mg, 0.40 mmol) and pyrazin-2-amine (38.2 mg, 0.40 mmol) were combined and suspended in DMSO (2 mL). To the reaction was then added isocyanocyclohexane (49.9 uL, 0.40 mmol) followed by HC104 (1.2 uL, 0.02 mmol). The reaction was heated to 100C for 2 hours. Reaction was quenched with H20 and desired product precipitated out. Reaction was filtered and the crude precipitate was purified via ISCO chromatography (0-100% EtOAc:Hexanes). Product yield: 18.8 mg, 14.1%

Reference： [1]Patent: WO2019/70943,2019,A1 .Location in patent: Page/Page column 68-69
[2]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 1480 - 1483

47
[ 253801-04-6 ]
[ 108-00-9 ]
C₁₂H₁₆N₄ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 1480 - 1483

48
[ 253801-04-6 ]
[ 1287783-38-3 ]
[ 1287783-39-4 ]

Reference： [1]Patent: WO2011/42368,2011,A1

49
[ 253801-04-6 ]
[ 33561-24-9 ]
Sodium 1-cyanoprop-1-ene 2-oxide [ No CAS ]
[ 1287783-37-2 ]

Yield	Reaction Conditions	Operation in experiment
23%	With acetic acid; In pentan-1-ol; at 105℃;	A mixture of 250 mg (1.71 mmol) lH-indazole-5-carbaldehyde, 180 mg (1.71 mmol) sodium l-cyanoprop-l-en-2-olate and 931 mg (6.84 mmol) 3-amino-4,4,4-trifluorobut-2-enenitrile [preparation: A.W. Lutz, US Patent 3,635,977; C.G. Krespan, J. Org. Chem. 34, 42 (1969)] in 1-pentanol (2.5 ml) and acetic acid (0.15 ml) was heated to 105C overnight. After cooling, the reaction mixture was diluted with THF and directly purified by preparative RP-HPLC (acetonitrile/water + 0.1%> TFA gradient) yielding 131 mg (23%> of th.) of the racemic title compound. LC-MS (method 2): Rt = 0.93 min; MS (ESIpos): m/z = 330 (M+H)'H-NMR (400 MHz, DMSO-dg): delta = 13.19 (br. s, 1H), 10.30 (s, 1H), 8.12 (s, 1H), 77.63 (d, 1H), 7.32 (d, 1H), 4.79 (s, 1H), 2.12 (s, 3H) ppm.

Reference： [1]Patent: WO2011/42368,2011,A1 .Location in patent: Page/Page column 53; 54

50
[ 253801-04-6 ]
3-amino-4,4-difluorobut-2-enenitrile [ No CAS ]
[ 1287783-41-8 ]

Yield	Reaction Conditions	Operation in experiment
48%	With acetic acid; for 5h;Reflux; Molecular sieve;	A mixture of 80 mg (0.55 mmol) lH-indazole-5-carbaldehyde, 142 mg (1.21 mmol) 3-amino-4,4- difluorobut-2-enenitrile [obtainable by Thorpe reaction of acetonitrile with 2,2-difluoroacetonitrile, cf. Org. React. 15, 1 (1967), ibid. 3J_, 1 (1984)] and a trace amount of powdered 4A molecular sieve in acetic acid (0.53 ml) was heated to reflux temperature for 5 h. After cooling, the reaction mixture was diluted with THF and filtered. The filtrate was directly purified by preparative RP-HPLC (acetonitrile/water + 0.1% TFA gradient) yielding 95 mg (48% of th.) of the title compound.LC-MS (method 4): Rt = 0.81 min; MS (ESIpos): m/z = 348 (M+H)+ 1H-NMR (400 MHz, DMSO-dg): delta = 13.21 (br. s, 1H), 10.70 (s, 1H), 8.16 (s, 1H), 7.72 (s, 1H), 7.66 (d, 1H), 7.32 (d, 1H), 6.82 (t, 2H), 4.90 (s, 1H) ppm.

Reference： [1]Patent: WO2011/42368,2011,A1 .Location in patent: Page/Page column 55; 56

51
[ 253801-04-6 ]
[ 20443-99-6 ]
[ 1312704-86-1 ]

Yield	Reaction Conditions	Operation in experiment
		A. 1-(2,4-Dichloro-benzyl)-<strong>[253801-04-6]1H-indazole-5-carbaldehyde</strong> was prepared from <strong>[253801-04-6]1H-indazole-5-carbaldehyde</strong> and 1-bromomethyl-2,4-dichloro-benzene following General Procedure A. LC/MS: mass calcd. for C15H10Cl2N2O (m/z), 305.1; found, 305.1 [M+H]+

Reference： [1]Patent: US2011/200587,2011,A1

52
[ 253801-04-6 ]
[ 140690-56-8 ]
[ 1312704-79-2 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; In N,N-dimethyl-formamide; at 100℃; for 16h;	A solution of 1H-Indazole-5-carbaldehyde (7.6 g, 52.0 mmol) and an appropriate substituted benzyl bromide (62.1 mmol) in DMF (120 mL) was treated with Cs2CO3 (17 g, 52.1 mmol), and the mixture was heated in an oil bath at 100 C. for 16 h. The reaction was cooled to RT and partitioned between EtOAc and H2O. The organic phase was washed with water (3×), brine, dried over Na2SO4 and concentrated in vacuo. Silica gel chromatography (EtOAc/hexanes) afforded the desired isomer. Recrystallization of the desired isomer from EtOAc/Hexanes afforded the desired pure aldehyde isomer. 1-(2,4-Bis-trifluoromethyl-benzyl)-<strong>[253801-04-6]1H-indazole-5-carbaldehyde</strong> was prepared from 1H-Indazole-5-carbaldehyde and 1-bromomethyl-2,4-bis-trifluoromethyl-benzene following General Procedure A.1H NMR (400 MHz, CDCl3): delta 10.08 9s, 1H), 8.34 (s, 1H), 8.31 (s, 1H), 7.99 (s, 1H), 7.95 (dd, 1H), 7.63 (d, 1H), 7.37 (d, 1H), 6.82 (d, 1H), 5.91 (s, 2H).LC/MS: mass calcd. for C17H10F6N2O: 372.07, found 373.2 [M+H]+.
		A. 1-(2,4-Bis-trifluoromethyl-benzyl)-<strong>[253801-04-6]1H-indazole-5-carbaldehyde</strong> was prepared from 1H-Indazole-5-carbaldehyde and 1-bromomethyl-2,4-bis-trifluoromethyl-benzene following General Procedure A. 1H NMR (400 MHz, CDCl3): delta 10.08 9s, 1H), 8.34 (s, 1H), 8.31 (s, 1H), 7.99 (s, 1H), 7.95 (dd, 1H), 7.63 (d, 1H), 7.37 (d, 1H), 6.82 (d, 1H), 5.91 (s, 2H). LC/MS: mass calcd. for C17H10F6N2O: 372.07. found 373.2 [M+H]+
		A. 1-(2,4-Bis-trifluoromethyl-benzyl)-<strong>[253801-04-6]1H-indazole-5-carbaldehyde</strong> was prepared from 1H-Indazole-5-carbaldehyde and 1-bromomethyl-2,4-bis-trifluoromethyl-benzene following General Procedure A. 1H NMR (400 MHz, CDCl3): delta 10.08 (s, 1H), 8.34 (s, 1H), 8.31 (s, 1H), 7.99 (s, 1H), 7.95 (dd, 1H), 7.63 (d, 1H), 7.37 (d, 1H), 6.82 (d, 1H), 5.91 (s, 2H). LC/MS (m/z) [M+1]+ 373.2 (calculated for C17H10F6N2O, 372.07).

		A. 1-(2,4-Bis-trifluoromethyl-benzyl)-<strong>[253801-04-6]1H-indazole-5-carbaldehyde</strong> was prepared from 1H-Indazole-5-carbaldehyde and 1-bromomethyl-2,4-bis-trifluoromethyl-benzene following General Procedure A. 1H NMR (CDCl3): delta 10.08 9s, 1H), 8.34 (s, 1H), 8.31 (s, 1H), 7.99 (s, 1H), 7.95 (dd, 1H), 7.63 (d, 1H), 7.37 (d, 1H), 6.82 (d, 1H), 5.91 (s, 2H). LC/MS: mass calcd. for C17H10F6N2O: 372.07, found 373.2 [M+H]+
		A. 1-(2,4-Bis-trifluoromethyl-benzyl)-<strong>[253801-04-6]1H-indazole-5-carbaldehyde</strong> was prepared from 1H-Indazole-5-carbaldehyde and 1-bromomethyl-2,4-bis-trifluoromethyl-benzene following General Procedure A. 1H NMR (CDCl3): delta 10.08 (s, 1H), 8.34 (s, 1H), 8.31 (s, 1H), 7.99 (s, 1H), 7.95 (dd, 1H), 7.63 (d, 1H), 7.37 (d, 1H), 6.82 (d, 1H), 5.91 (s, 2H). LC/MS (m/z) [M+1]+373.2 (calculated for C17H10F6N2O, 372.07).

Reference： [1]Patent: US2011/150864,2011,A1 .Location in patent: Page/Page column 145-146
[2]Patent: US2011/200586,2011,A1
[3]Patent: US2011/200586,2011,A1
[4]Patent: US2011/200587,2011,A1
[5]Patent: US2011/200587,2011,A1

53
[ 253801-04-6 ]
[ 1312701-78-2 ]

Reference： [1]Patent: US2011/150864,2011,A1

54
[ 253801-04-6 ]
[ 1312704-81-6 ]

Reference： [1]Patent: US2011/150864,2011,A1
[2]Patent: US2011/200586,2011,A1

55
[ 253801-04-6 ]
5-[1-(2,4-Bis-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-ethylsulfanyl-thiazol-4-one [ No CAS ]

Reference： [1]Patent: US2011/200586,2011,A1

56
[ 253801-04-6 ]
5-[1-(4-Chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-propylsulfanyl-thiazol-4-one [ No CAS ]

Reference： [1]Patent: US2011/200587,2011,A1

57
[ 253801-04-6 ]
[ 853368-32-8 ]
[ 1312704-85-0 ]

Yield	Reaction Conditions	Operation in experiment
		B. 4-(5-Formyl-indazol-1-ylmethyl)-3-trifluoromethyl-benzonitrile was prepared from 4-bromomethyl-3-trifluoromethyl-benzonitrile and <strong>[253801-04-6]1H-indazole-5-carbaldehyde</strong> following General Procedure A. LC/MS: mass calcd. for C17H10F3N3O (m/z), 329.2. found, 330.2 [M+H]+.

Reference： [1]Patent: US2011/200586,2011,A1

58
[ 253801-04-6 ]
[ 934557-65-0 ]
[ 1312704-88-3 ]

Yield	Reaction Conditions	Operation in experiment
		E. 1-(4-Methanesulfonyl-2-trifluoromethyl-benzyl)-<strong>[253801-04-6]1H-indazole-5-carbaldehyde</strong> was prepared from <strong>[253801-04-6]1H-indazole-5-carbaldehyde</strong> and 1-bromomethyl-4-methanesulfonyl-2-trifluoromethyl-benzene following General Procedure A. 1H NMR (400 MHz, CDCl3): delta 10.08 (s, 1H), 8.31-8.36 (3H), 7.97 (dd, 1H), 7.95 (dd, 1H), 7.38 (d, 1H), 6.91 (d, 1H), 5.94 (s, 2H), 3.06 (s, 3H).

Reference： [1]Patent: US2011/200586,2011,A1

59
[ 253801-04-6 ]
[ 886496-75-9 ]
[ 1312704-84-9 ]

Yield	Reaction Conditions	Operation in experiment
		A. 1-(4-Chloro-2-trifluoromethyl-benzyl)-<strong>[253801-04-6]1H-indazole-5-carbaldehyde</strong> was prepared from <strong>[253801-04-6]1H-indazole-5-carbaldehyde</strong> and 1-bromomethyl-4-chloro-2-trifluoromethyl-benzene following General Procedure A. 1H NMR (400 MHz, CDCl3) delta 10.07 (s, 1H), 8.32 (s, 1H), 8.29 (s, 1H), 7.94 (dd, 1H), 7.73 (d, 1H), 7.38-7.33 (m, 2H), 6.66 (d, 1H), 5.82 (s, 2H). LC/MS (m/z) [M+1]+ 339.1 (calculated for C25H23ClF3N5O3S2, 338.71).
		A. 1-(4-Chloro-2-trifluoromethyl-benzyl)-<strong>[253801-04-6]1H-indazole-5-carbaldehyde</strong> was prepared from <strong>[253801-04-6]1H-indazole-5-carbaldehyde</strong> and 1-bromomethyl-4-chloro-2-trifluoromethyl-benzene following General Procedure A. 1H NMR (400 MHz, CDCl3) delta 10.07 (s, 1H), 8.32 (s, 1H), 8.29 (s, 1H), 7.94 (dd, 1H), 7.73 (d, 1H), 7.38-7.33 (m, 2H), 6.66 (d, 1H), 5.82 (s, 2H). LC/MS (m/z) [M+1]+ 339.1 (calculated for C25H23ClF3N5O3S2, 338.71).
		A. 1-(4-Chloro-2-trifluoromethyl-benzyl)-<strong>[253801-04-6]1H-indazole-5-carbaldehyde</strong> was prepared from <strong>[253801-04-6]1H-indazole-5-carbaldehyde</strong> and 1-bromomethyl-4-chloro-2-trifluoromethyl-benzene following General Procedure A. LC/MS: mass calcd. for C16H10ClF3N2O (m/z), 338.71; found, 339.1 [M+H]+

		A. 1-(4-Chloro-2-trifluoromethyl-benzyl)-<strong>[253801-04-6]1H-indazole-5-carbaldehyde</strong> was prepared from <strong>[253801-04-6]1H-indazole-5-carbaldehyde</strong> and 1-bromomethyl-4-chloro-2-trifluoromethyl-benzene following General Procedure A. 1H NMR (400 MHz, CDCl3) delta 10.07 (s, 1H), 8.32 (s, 1H), 8.29 (s, 1H), 7.94 (dd, 1H), 7.73 (d, 1H), 7.38-7.33 (m, 2H), 6.66 (d, 1H), 5.82 (s, 2H) LC/MS (m/z) [M+1]+339.1 (calculated for C25H23ClF3N5O3S2, 338.71).
	With caesium carbonate; In N,N-dimethyl-formamide; at 90℃; for 16h;	General Procedure A: A solution of the heteroarylcarbaldehyde (<strong>[253801-04-6]1H-indazole-5-carbaldehyde</strong>, 1H-indole-5-carbaldehyde or 1H-benzotriazole-5-carbaldehyde; 52.0 mmol), heteroaryl bromide (3-methyl-5-bromo-1H-indazole; 52.0 mmol) or heteroaryl carboxylic ester (methyl 1H-benzotriazole-5-carboxylate; 52.0 mmol) and an appropriately substituted benzyl bromide (62.1 mmol) in DMF (120 mL) was treated with Cs2CO3 (17 g, 52.1 mmol), and the mixture was heated at 90 C. for 16 h. The reaction was cooled to rt and partitioned between EtOAc and H2O. The organic phase was washed with water (3×), brine, dried (Na2SO4) and concentrated in vacuo. Silica gel chromatography (EtOAc/hexane or DCM/hexane) afforded the desired substituted 1-benzyl-1H-heteroarylcarbaldehyde or 1-benzyl-1H-heteroaryl bromide isomer.A) [4-Chloro-2-(trifluoromethyl)benzyl]-1H-indazol-5-carbaldehyde was prepared from 4-chloro-2-(trifluoromethyl)benzyl bromide and 1H-indazol-5-carbaldehyde following General Procedure A.

Reference： [1]Patent: US2011/200586,2011,A1
[2]Patent: US2011/200586,2011,A1
[3]Patent: US2011/200587,2011,A1
[4]Patent: US2011/200587,2011,A1
[5]Patent: US2011/294780,2011,A1 .Location in patent: Page/Page column 130-131; 133

60
[ 253801-04-6 ]
[ 916420-86-5 ]
[ 1312704-90-7 ]

Yield	Reaction Conditions	Operation in experiment
		B. 1-(4-Methoxy-2-trifluoromethyl-benzyl)-<strong>[253801-04-6]1H-indazole-5-carbaldehyde</strong> was prepared from 1-bromomethyl-4-methoxy-2-trifluoromethyl-benzene and <strong>[253801-04-6]1H-indazole-5-carbaldehyde</strong> following General Procedure A. LC/MS: mass calcd. for C17H13F3N2O2 (m/z), 334.2. found, 335.2 [M+H]+.
		B. 1-(4-Methoxy-2-trifluoromethyl-benzyl)-<strong>[253801-04-6]1H-indazole-5-carbaldehyde</strong> was prepared from 1-bromomethyl-4-methoxy-2-trifluoromethyl-benzene and <strong>[253801-04-6]1H-indazole-5-carbaldehyde</strong> following General Procedure A. LC/MS: mass calcd. for C17H13F3N2O2 (m/z), 334.2; found, 335.2 [M+H]+

Reference： [1]Patent: US2011/200586,2011,A1
[2]Patent: US2011/200587,2011,A1

61
[ 253801-04-6 ]
[ 1312702-83-2 ]

Reference： [1]Patent: US2011/150864,2011,A1

62
[ 253801-04-6 ]
[ 1312704-82-7 ]

Reference： [1]Patent: US2011/150864,2011,A1

63
[ 253801-04-6 ]
[ 1312705-81-9 ]

Reference： [1]Patent: US2011/150864,2011,A1

64
[ 253801-04-6 ]
[ 141-84-4 ]
[ 1312704-84-9 ]
5-[1-(4-Chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-thioxo-thiazolidin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		B. 5-[1-(4-Chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-thioxo-thiazolidin-4-one was prepared from 1-(4-Chloro-2-trifluoromethyl-benzyl)-<strong>[253801-04-6]1H-indazole-5-carbaldehyde</strong> was prepared from <strong>[253801-04-6]1H-indazole-5-carbaldehyde</strong> and 2-thioxo-thiazolidin-4-one following General Procedure B. 1H NMR (400 MHz, DMSO) delta 8.37 (s, 1H), 8.15 (s, 1H), 7.89 (d, 1H), 7.82-7.79 (m, 2H), 7.67-7.65 (m, 2H), 6.77 (d, 1H), 5.87 (s, 2H). LC/MS (m/z) [M+1]+ 454.0 (calculated for C25H23ClF3N5O3S2, 453.89).
		B. 5-[1-(4-Chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-thioxo-thiazolidin-4-one was prepared from 1-(4-Chloro-2-trifluoromethyl-benzyl)-<strong>[253801-04-6]1H-indazole-5-carbaldehyde</strong> was prepared from <strong>[253801-04-6]1H-indazole-5-carbaldehyde</strong> and 2-thioxo-thiazolidin-4-one following General Procedure B. 1H NMR (400 MHz, DMSO) delta 8.37 (s, 1H), 8.15 (s, 1H), 7.89 (d, 1H), 7.82-7.79 (m, 2H), 7.67-7.65 (m, 2H), 6.77 (d, 1H), 5.87 (s, 2H). LC/MS (m/z) [M+1]+ 454.0 (calculated for C25H23ClF3N5O3S2, 453.89).
		B. 5-[1-(4-Chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-thioxo-thiazolidin-4-one was prepared from 1-(4-Chloro-2-trifluoromethyl-benzyl)-<strong>[253801-04-6]1H-indazole-5-carbaldehyde</strong> was prepared from <strong>[253801-04-6]1H-indazole-5-carbaldehyde</strong> and 2-thioxo-thiazolidin-4-one following General Procedure B. 1H NMR (400 MHz, DMSO) delta 8.37 (s, 1H), 8.15 (s, 1H), 7.89 (d, 1H), 7.82-7.79 (m, 2H), 7.67-7.65 (m, 2H), 6.77 (d, 1H), 5.87 (s, 2H) LC/MS (m/z) [M+1]+454.0 (calculated for C25H23ClF3N5O3S2, 453.89).

Reference： [1]Patent: US2011/200586,2011,A1
[2]Patent: US2011/200586,2011,A1
[3]Patent: US2011/200587,2011,A1

65
[ 253801-04-6 ]
5-[1-(2,4-bis-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-methylsulfanyl-thiazol-4-one [ No CAS ]

Reference： [1]Patent: US2011/200586,2011,A1

66
[ 253801-04-6 ]
2-[Bis-(2-hydroxy-ethyl)-amino]-5-[1-(4-chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-thiazol-4-one [ No CAS ]

Reference： [1]Patent: US2011/200586,2011,A1

67
[ 253801-04-6 ]
2S-({5-[1-(4-Chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-yl}-methyl-amino)-3-hydroxy-propionic acid [ No CAS ]

Reference： [1]Patent: US2011/200586,2011,A1

68
[ 253801-04-6 ]
5-[1-(4-Chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-[methyl-(2-pyrrolidin-1-yl-ethyl)-amino]-thiazol-4-one [ No CAS ]

Reference： [1]Patent: US2011/200586,2011,A1

69
[ 253801-04-6 ]
5-[1-(4-Chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-[methyl-(1-methyl-piperidin-4-yl)amino]-thiazol-4-one [ No CAS ]

Reference： [1]Patent: US2011/200586,2011,A1

70
[ 253801-04-6 ]
5-[1-(2,4-Bis-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-[methyl-(1-methyl-piperidin-4-yl)-amino]-thiazol-4-one [ No CAS ]

Reference： [1]Patent: US2011/200586,2011,A1

71
[ 253801-04-6 ]
5-[1-(2,4-Bis-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-[(5-methoxymethyl-pyrrolidin-3-yl)-methyl-amino]-thiazol-4-one [ No CAS ]

Reference： [1]Patent: US2011/200586,2011,A1

72
[ 253801-04-6 ]
5-[1-(4-Chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-[(5-methoxymethyl-pyrrolidin-3-yl)-methyl-amino]-thiazol-4-one [ No CAS ]

Reference： [1]Patent: US2011/200586,2011,A1

73
[ 253801-04-6 ]
5-[1-(4-Chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-[(5-hydroxymethyl-pyrrolidin-3-yl)-methyl-amino]-thiazol-4-one [ No CAS ]

Reference： [1]Patent: US2011/200586,2011,A1

74
[ 253801-04-6 ]
5-[1-(2,4-Bis-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-[(5-hydroxymethyl-pyrrolidin-3-yl)-methyl-amino]-thiazol-4-one [ No CAS ]

Reference： [1]Patent: US2011/200586,2011,A1

75
[ 253801-04-6 ]
[ 1327336-38-8 ]

Reference： [1]Patent: US2011/200586,2011,A1

76
[ 253801-04-6 ]
5-[1-(2,4-Bis-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-dimethylamino-thiazol-4-one [ No CAS ]

Reference： [1]Patent: US2011/200586,2011,A1

77
[ 253801-04-6 ]
5-[1-(2,4-Bis-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-[(2-dimethylamino-ethyl)-methyl-amino]-thiazol-4-one [ No CAS ]

Reference： [1]Patent: US2011/200586,2011,A1

78
[ 253801-04-6 ]
5-[1-(4-Chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-thioxo-thiazolidin-4-one [ No CAS ]

Reference： [1]Patent: US2011/200586,2011,A1

79
[ 253801-04-6 ]
5-[1-(4-chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-ethylsulfanyl-thiazolidin-4-one [ No CAS ]

Reference： [1]Patent: US2011/200586,2011,A1

80
[ 253801-04-6 ]
5-[1-(4-Chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-[(2-dimethylamino-ethyl)-methyl-amino]-thiazol-4-one [ No CAS ]

Reference： [1]Patent: US2011/200586,2011,A1

81
[ 253801-04-6 ]
5-[1-(4-Chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-[(2,3-dihydroxy-propyl)-methyl-amino]-thiazol-4-one [ No CAS ]

Reference： [1]Patent: US2011/200586,2011,A1

82
[ 253801-04-6 ]
2-[Bis-(2-methoxy-ethyl)-amino]-5-[1-(4-methoxy-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-thiazol-4-one [ No CAS ]

Reference： [1]Patent: US2011/200586,2011,A1

83
[ 253801-04-6 ]
2-[Bis-(2-methoxy-ethyl)-amino]-5-[1-(3-chloro-5-trifluoromethyl-pyridin-2-ylmethyl)-1H-indazol-5-ylmethylene]-thiazol-4-one [ No CAS ]

Reference： [1]Patent: US2011/200586,2011,A1

84
[ 253801-04-6 ]
5-[1-(3-Chloro-5-trifluoromethyl-pyridin-2-ylmethyl)-1H-indazol-5-ylmethylene]-2-[(2,3-dihydroxy-propyl)-methyl-amino]-thiazol-4-one [ No CAS ]

Reference： [1]Patent: US2011/200586,2011,A1

85
[ 253801-04-6 ]
2-[Bis-(2-hydroxy-ethyl)-amino]-5-[1-(3-chloro-5-trifluoromethyl-pyridin-2-ylmethyl)-1H-indazol-5-ylmethylene]-thiazol-4-one [ No CAS ]

Reference： [1]Patent: US2011/200586,2011,A1

86
[ 253801-04-6 ]
2-[(2,3-Dihydroxy-propyl)-methyl-amino]-5-[1-(4-methoxy-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-thiazol-4-one [ No CAS ]

Reference： [1]Patent: US2011/200586,2011,A1

87
[ 253801-04-6 ]
2-[Bis-(2-methoxy-ethyl)-amino]-5-[1-(4-chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-thiazol-4-one [ No CAS ]

Reference： [1]Patent: US2011/200586,2011,A1

88
[ 253801-04-6 ]
5-[1-(4-Chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-(methyl-piperidin-4-yl-amino)-thiazol-4-one [ No CAS ]

Reference： [1]Patent: US2011/200586,2011,A1

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H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 253801-04-6 ] {[proInfo.proName]}

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[ 253801-04-6 ] Synthesis Path-Upstream 1~7

[ 253801-04-6 ] Synthesis Path-Downstream 1~88

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Aldehydes

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Indazoles

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