[ CAS No. 677306-38-6 ]

Name: 677306-38-6|1H-Indazole-4-carboxylic acid|97%
Brand: Ambeed
SKU: A503101
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Quality Control of [ 677306-38-6 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 677306-38-6 ]

SDS Specification

Alternatived Products of [ 677306-38-6 ]

Product Details of [ 677306-38-6 ]

CAS No. :	677306-38-6	MDL No. :	MFCD03840644
Formula :	C₈H₆N₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	KGKZHHIUOZGUNP-UHFFFAOYSA-N
M.W :	162.15 g/mol	Pubchem ID :	21982323
Synonyms :

Calculated chemistry of [ 677306-38-6 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	9
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	2.0
Molar Refractivity :	43.05
TPSA :	65.98 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.52 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.46
Log Po/w (XLOGP3) :	1.08
Log Po/w (WLOGP) :	1.26
Log Po/w (MLOGP) :	0.72
Log Po/w (SILICOS-IT) :	1.38
Consensus Log Po/w :	0.98

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.85

Water Solubility

Log S (ESOL) :	-2.01
Solubility :	1.57 mg/ml ; 0.00967 mol/l
Class :	Soluble
Log S (Ali) :	-2.06
Solubility :	1.42 mg/ml ; 0.00876 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.27
Solubility :	0.863 mg/ml ; 0.00532 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.27

Safety of [ 677306-38-6 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 677306-38-6 ]

* 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 [ 677306-38-6 ]
Downstream synthetic route of [ 677306-38-6 ]

[ 677306-38-6 ] Synthesis Path-Upstream 1~6

1
[ 677306-38-6 ]
[ 18107-18-1 ]
[ 192945-49-6 ]

Yield	Reaction Conditions	Operation in experiment
50%	at 20℃;	Synthesis of lH-Indazole-4-carboxylic acid methyl ester (18a): To a solution of lH-Indazole-4-carboxylic acid (lOOmg, 0.62 mmol) in 6 mL of methanol-dichloromethane (1 : 1) was added trimethylsilyl diazomethane (2.0 M in ethyl ether) dropwise at room temperature. More trimethylsilyl diazomethane was added until the starting material disappeared. Solvent was removed carefully and the residue was purified by column chromatography (50percent ethyl acetate/hexanes). The product (54 mg, 50percent) was obtained as a colorless solid. MS (ES) M+H expected = 177.1, found = 177.2.

Reference： [1] Patent: WO2007/51062, 2007, A2, . Location in patent: Page/Page column 127-128
[2] Patent: WO2011/49917, 2011, A1, . Location in patent: Page/Page column 42-43
[3] Patent: WO2009/134666, 2009, A1, . Location in patent: Page/Page column 50

2
[ 186407-74-9 ]
[ 677306-38-6 ]

Yield	Reaction Conditions	Operation in experiment
55%	Stage #1: With sodium hydride In tetrahydrofuran; mineral oil at 20℃; for 0.5 h; Stage #2: With sec.-butyllithium In cyclohexane at -50℃; for 2 h; Stage #3: for 1 h;	To a solution of bromoindazole (1.00 eqiv) in anhydrous tetrahydrofuran (7 L/mol) at room temperature was added sodium hydride (60percent in mineral oil, 1.11 eqiv) in several portions. The resulting solution was maintained for 30 min at room temperature and was then cooled to-60 C.A 1.3 M solution of sec-butyllithium in cyclohexane (2.1 eqiv) was added to the reaction mixture while maintaining the internal temperature below-50 C. The mixture was maintained for an additional 2 h at -50 C. A steady stream of anhydrous carbon dioxide was bubbled through the reaction mixture for 1 h. The flow was continued while the reaction mixture was allowed to warm to room temperature. Brine (6 L/mol) was added and the pH of the mixture was adjusted to 5 with concentrated hydrochloric acid. The mixture was extracted with warm ethyl acetate (3 x 8 L/mol) and the combined extracts were washed with small volume of brine, dried over anhydrous sodium sulfate, and concentrated. The product was purified by chromatography on silica gel or by crystallization

Reference： [1] Patent: WO2004/29050, 2004, A1, . Location in patent: Page 103;104

3
[ 192945-49-6 ]
[ 677306-38-6 ]

Yield	Reaction Conditions	Operation in experiment
87%	Stage #1: With sodium hydroxide In ethanol; waterHeating / reflux Stage #2: With hydrogenchloride In water	A solution of sodium hydroxide (1.70 g, 42.6 mmol) in water (25 ml) was added to a solution of methyl 1H-indazole-4-carboxylate (Description 9,2. 50 g, 14.2 mmol) in ethanol (50 ml) and the resulting mixture heated at reflux overnight. The ethanol was removed from the cooled reaction mixture by evaporation and the aqueous phase then acidified by the addition of conc. HCI. The resultant precipitate was collected by filtration and dried under vacuum to give the title compound as an orange solid (2.0 g, 87percent). H NMR (400 MHZ, DMSO-D6) 8 7. 48 (lH, m), 7.81 (1H, dd, J7.4 and 0. 7), 7.85 (1H, dd, J 8. 4 and 0.8), 8.42 (1H, d, J0.8), 9.20 (1H, br s).
56%	Stage #1: With water; sodium hydroxide In methanol for 6 h; Reflux Stage #2: With hydrogenchloride In waterCooling with ice	To a stirred solution of indazole-4-carboxylic acid methyl ester (0.3 g 1.7 mmol) in 10 mL methanol, NaOH (0.27 g, 6.8 mmol) in 2 mL of water was added and the reaction mixture was refluxed for 6 h. The reaction was cooled and the solvent was evaporated under reduced pressure and 2 mL of water was added. The solution was cooled on ice and compound was precipitated by adding concentrated HCl drop-wise. The resulting yellow precipitate was collected and washed with acidic water and dried (0.15 g, 56percent). m.p. 223-226° C. ¹H NMR (400 MHz, DMSO-d₆, TMS) δ 10.20 (bs, 2H), 7.75 (d, 1H), 7.60 (d, 1H), 7.35 (d, 1H), 7.28 (t, 1H).

Reference： [1] Patent: WO2005/28445, 2005, A2, . Location in patent: Page/Page column 29
[2] Patent: US2012/130078, 2012, A1, . Location in patent: Page/Page column 6

4
[ 598-30-1 ]
[ 677306-38-6 ]

Yield	Reaction Conditions	Operation in experiment
30%	Stage #1: With sodium hydride In tetrahydrofuran at 20℃; for 0.5 h; Cooling with acetone-dry ice Stage #2: at -50 - 50℃; for 2 h; Stage #3: at -50℃; for 1 h;	To a cooled (water/ice bath) solution of bromomethylaniline (1.00 equiv. ) in chloroform (1.5 mL/mol) was added acetic anhydride (2.27 equiv. ) maintaining the temperature below 40 °C. The mixture was stirred at room temperature for 1 h. Potassium acetate (0.29 eq) was added followed by isoamyl nitrite (2.15 equiv. ). The reaction mixture was heated overnight to reflux. Volatiles were removed on vacuum rotary evaporator. Water (0.65 L/mol) was added to the residue and the mixture was again concentrated in vacuum. Hydrochloric acid (11 N, 1 L/mol) was added to the residue and the mixture was vigorously stirred and heated to 50°C for 2 h. The mixture was cooled to room temperature and pH was adjusted to 10 with 50percent aqueous sodium hydroxide while maintaining the temperature below 25 °C. The mixture was diluted with water (0.65 L/mol) and extracted with ethyl acetate (2 x 1.2 L/mol). The combined extracts were washed with brine (1 L/mol) and dried over anhydrous sodium sulfate. The organic solution was filtered through a plug of silica gel. The plug was further eluted with ethyl acetate. The solvent was removed on vacuum rotary evaporator, and the residue was triturated with heptane (1 L/mol). The solid material was collected by filtration, rinsed with heptane, and dried to provide the bromoindazole in 60-70percent yield. To a solution of the bromoindazole (1.00 equiv. ) in anhydrous THF (7 L/mol) was added sodium hydride (60percent in mineral oil, 1.11 equiv. ) in several portions at room temperature. The resulting solution was stirred 30 min at room temperature then cooled in dry ice/acetone bath. sec-Butyllithium (1.3 M in cyclohexane, 2.11 equiv. ) was added to the reaction mixture maintaining the temperature below -50 °C. The mixture was stirred 2 h at -50 °C. Anhydrous carbon dioxide was bubbled, through the reaction mixture at temperature below-40 °C for 1 h. The reaction was allowed to reach room temperature while keeping steady flow of carbon dioxide through the mixture. Brine (6 L/mol) was added and pH of the mixture was adjusted to 5 with concd. hydrochloric acid. The mixture was extracted with warm ethyl acetate (3 x 8 L/mol). The combined extracts were washed with small volume of brine, dried over anhydrous sodium sulfate and concentrated. The product was purified by chromatography on silica gel or by crystallization to provide the acid in 30-60percent yield. The acid was coupled with 1,4- diazabicyclo[3.2.2]nonane according to procedure A. The following acid was prepared by this method: 177-Indazole-4-carboxylic acid.

Reference： [1] Patent: WO2005/111038, 2005, A2, . Location in patent: Page/Page column 65-66

5
[ 2258-42-6 ]
[ 186407-74-9 ]
[ 677306-38-6 ]

Reference： [1] Synthetic Communications, 2012, vol. 42, # 5, p. 658 - 666

6
[ 18583-89-6 ]
[ 677306-38-6 ]

Reference： [1] Patent: US2012/130078, 2012, A1,

[ 677306-38-6 ] Synthesis Path-Downstream 1~59

1
[ 186407-74-9 ]
[ 677306-38-6 ]

Yield	Reaction Conditions	Operation in experiment
55%		To a solution of bromoindazole (1.00 eqiv) in anhydrous tetrahydrofuran (7 L/mol) at room temperature was added sodium hydride (60% in mineral oil, 1.11 eqiv) in several portions. The resulting solution was maintained for 30 min at room temperature and was then cooled to-60 C.A 1.3 M solution of sec-butyllithium in cyclohexane (2.1 eqiv) was added to the reaction mixture while maintaining the internal temperature below-50 C. The mixture was maintained for an additional 2 h at -50 C. A steady stream of anhydrous carbon dioxide was bubbled through the reaction mixture for 1 h. The flow was continued while the reaction mixture was allowed to warm to room temperature. Brine (6 L/mol) was added and the pH of the mixture was adjusted to 5 with concentrated hydrochloric acid. The mixture was extracted with warm ethyl acetate (3 x 8 L/mol) and the combined extracts were washed with small volume of brine, dried over anhydrous sodium sulfate, and concentrated. The product was purified by chromatography on silica gel or by crystallization

Reference： [1]Patent: WO2004/29050,2004,A1 .Location in patent: Page 103;104

2
[ 192945-49-6 ]
[ 677306-38-6 ]

Yield	Reaction Conditions	Operation in experiment
87%		A solution of sodium hydroxide (1.70 g, 42.6 mmol) in water (25 ml) was added to a solution of <strong>[192945-49-6]methyl 1H-indazole-4-carboxylate</strong> (Description 9,2. 50 g, 14.2 mmol) in ethanol (50 ml) and the resulting mixture heated at reflux overnight. The ethanol was removed from the cooled reaction mixture by evaporation and the aqueous phase then acidified by the addition of conc. HCI. The resultant precipitate was collected by filtration and dried under vacuum to give the title compound as an orange solid (2.0 g, 87%). H NMR (400 MHZ, DMSO-D6) 8 7. 48 (lH, m), 7.81 (1H, dd, J7.4 and 0. 7), 7.85 (1H, dd, J 8. 4 and 0.8), 8.42 (1H, d, J0.8), 9.20 (1H, br s).
56%		To a stirred solution of <strong>[192945-49-6]indazole-4-carboxylic acid methyl ester</strong> (0.3 g 1.7 mmol) in 10 mL methanol, NaOH (0.27 g, 6.8 mmol) in 2 mL of water was added and the reaction mixture was refluxed for 6 h. The reaction was cooled and the solvent was evaporated under reduced pressure and 2 mL of water was added. The solution was cooled on ice and compound was precipitated by adding concentrated HCl drop-wise. The resulting yellow precipitate was collected and washed with acidic water and dried (0.15 g, 56%). m.p. 223-226 C. 1H NMR (400 MHz, DMSO-d6, TMS) delta 10.20 (bs, 2H), 7.75 (d, 1H), 7.60 (d, 1H), 7.35 (d, 1H), 7.28 (t, 1H).

Reference： [1]Patent: WO2005/28445,2005,A2 .Location in patent: Page/Page column 29
[2]Patent: US2012/130078,2012,A1 .Location in patent: Page/Page column 6

3
[ 598-30-1 ]
[ 677306-38-6 ]

Yield	Reaction Conditions	Operation in experiment
30 - 60%		To a cooled (water/ice bath) solution of bromomethylaniline (1.00 equiv. ) in chloroform (1.5 mL/mol) was added acetic anhydride (2.27 equiv. ) maintaining the temperature below 40 C. The mixture was stirred at room temperature for 1 h. Potassium acetate (0.29 eq) was added followed by isoamyl nitrite (2.15 equiv. ). The reaction mixture was heated overnight to reflux. Volatiles were removed on vacuum rotary evaporator. Water (0.65 L/mol) was added to the residue and the mixture was again concentrated in vacuum. Hydrochloric acid (11 N, 1 L/mol) was added to the residue and the mixture was vigorously stirred and heated to 50C for 2 h. The mixture was cooled to room temperature and pH was adjusted to 10 with 50% aqueous sodium hydroxide while maintaining the temperature below 25 C. The mixture was diluted with water (0.65 L/mol) and extracted with ethyl acetate (2 x 1.2 L/mol). The combined extracts were washed with brine (1 L/mol) and dried over anhydrous sodium sulfate. The organic solution was filtered through a plug of silica gel. The plug was further eluted with ethyl acetate. The solvent was removed on vacuum rotary evaporator, and the residue was triturated with heptane (1 L/mol). The solid material was collected by filtration, rinsed with heptane, and dried to provide the bromoindazole in 60-70% yield. To a solution of the bromoindazole (1.00 equiv. ) in anhydrous THF (7 L/mol) was added sodium hydride (60% in mineral oil, 1.11 equiv. ) in several portions at room temperature. The resulting solution was stirred 30 min at room temperature then cooled in dry ice/acetone bath. sec-Butyllithium (1.3 M in cyclohexane, 2.11 equiv. ) was added to the reaction mixture maintaining the temperature below -50 C. The mixture was stirred 2 h at -50 C. Anhydrous carbon dioxide was bubbled, through the reaction mixture at temperature below-40 C for 1 h. The reaction was allowed to reach room temperature while keeping steady flow of carbon dioxide through the mixture. Brine (6 L/mol) was added and pH of the mixture was adjusted to 5 with concd. hydrochloric acid. The mixture was extracted with warm ethyl acetate (3 x 8 L/mol). The combined extracts were washed with small volume of brine, dried over anhydrous sodium sulfate and concentrated. The product was purified by chromatography on silica gel or by crystallization to provide the acid in 30-60% yield. The acid was coupled with 1,4- diazabicyclo[3.2.2]nonane according to procedure A. The following acid was prepared by this method: 177-Indazole-4-carboxylic acid.

Reference： [1]Patent: WO2005/111038,2005,A2 .Location in patent: Page/Page column 65-66

4
[ 677306-38-6 ]
[ 18107-18-1 ]
[ 192945-49-6 ]

Yield	Reaction Conditions	Operation in experiment
50%	In methanol; diethyl ether; dichloromethane; at 20℃;	Synthesis of lH-Indazole-4-carboxylic acid methyl ester (18a): To a solution of lH-Indazole-4-carboxylic acid (lOOmg, 0.62 mmol) in 6 mL of methanol-dichloromethane (1 : 1) was added trimethylsilyl diazomethane (2.0 M in ethyl ether) dropwise at room temperature. More trimethylsilyl diazomethane was added until the starting material disappeared. Solvent was removed carefully and the residue was purified by column chromatography (50% ethyl acetate/hexanes). The product (54 mg, 50%) was obtained as a colorless solid. MS (ES) M+H expected = 177.1, found = 177.2.
	In methanol; toluene; at 20℃;	Indazole-4-carboxylic acid (2.00 g, 12.3 mmol) is suspended in methanol (20 mL) and toluene (30 mL) at room temperature. A solution of 2M trimethylsilyl diazomethane (12 mL, 24 mmol) in toluene is added slowly and the mixture is stirred at room temperature until the solution turned yellow. The reaction is quenched with concentrated acetic acid (5 mL) and the solvent is removed in vacuo. The residue is purified by silica gel chromatography eluting with a gradient of 0-30% ethyl acetate in hexanes to afford lH-indazole-4-carboxylic acid methyl ester.
	In methanol; toluene; at 20℃;	Indazole-4-carboxylic acid (2.00 g, 12.3 mmol) was suspended in methanol (20 mL) and toluene (30 mL) at room temperature. A solution of 2 M trimethylsilyl diazomethane (12 mL, 24 mmol) in toluene was added slowly and the mixture was stirred at room temperature until the solution turned yellow. The reaction was quenched with concentrated acetic acid (5 mL) and the solvent was removed in vacuo. The residue was purified by silica gel chromatography eluting with a gradient of 0-30% ethyl acetate in hexanes to afford lH-indazole-4-carboxylic acid methyl ester.

Reference： [1]Patent: WO2007/51062,2007,A2 .Location in patent: Page/Page column 127-128
[2]Patent: WO2011/49917,2011,A1 .Location in patent: Page/Page column 42-43
[3]Patent: WO2009/134666,2009,A1 .Location in patent: Page/Page column 50

5
[ 2740-83-2 ]
[ 677306-38-6 ]
[ 1194019-70-9 ]

Yield	Reaction Conditions	Operation in experiment
		To a stirred room temperature solution of <strong>[677306-38-6]indazole-4-carboxylic acid</strong> (1.0 g, 6.1 mmol) in DMF (15 niL) was added PyBOP (3.5 g, 6.5 mmol) and triethylamine (0.90 g, 7.5 mmol). After 15 minutes, 3-trifluoromethyl-benzylamine (1.2 g, 7.0 mmol) was added. After 4 hours, the mixture was quenched with water (30 niL) and diluted with ethyl acetate (20 mL). The organic layer was separated, washed with brine (30 mL), dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography eluting with a gradient of 20-60% ethyl acetate in hexanes to afford lH-indazole-4- carboxylic acid 3-trifluoromethyl-benzylamide.

Reference： [1]Patent: WO2009/134666,2009,A1 .Location in patent: Page/Page column 47
[2]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 441 - 448

6
[ 677306-38-6 ]
[ 1044588-31-9 ]
[ 1044586-92-6 ]

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 4028 - 4037

7
[ 677306-38-6 ]
4-phenyldecahydroquinolin-4-ol [ No CAS ]
C₂₃H₂₅N₃O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 2359 - 2364

8
[ 677306-38-6 ]
[ 92729-14-1 ]
C₂₃H₂₅N₃O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 2359 - 2364

9
[ 677306-38-6 ]
[ 1194019-74-3 ]

Reference： [1]Patent: WO2011/49917,2011,A1
[2]Patent: WO2009/134666,2009,A1

10
[ 677306-38-6 ]
[ 1194019-76-5 ]

Reference： [1]Patent: WO2011/49917,2011,A1
[2]Patent: WO2009/134666,2009,A1

11
[ 2258-42-6 ]
[ 186407-74-9 ]
[ 677306-38-6 ]

Reference： [1]Synthetic Communications,2012,vol. 42,p. 658 - 666

12
[ 18583-89-6 ]
[ 677306-38-6 ]

Reference： [1]Patent: US2012/130078,2012,A1

13
[ 677306-38-6 ]
[ 1400661-63-3 ]
[ 1400663-08-2 ]

Yield	Reaction Conditions	Operation in experiment
		Example 44 Preparation of (S)-2-[5-(3-hydroxy-benzylcarbamoyl)-3-methyl-thiophene-2-carbonyl]-amino}-3-[(1H-indazole-4-carbonyl)-amino]-propionic acid (HCl salt) (S)-3-amino-2-[5-(3-hydroxy-benzylcarbamoyl)-3-methyl-thiophene-2-carbonyl]-amino}-propionic acid methyl ester (HCl salt) (100 mg, 0.23 mmol) was dissolved in DMF (2.5 ml) and the following reagents were successively added at rt: <strong>[677306-38-6]1H-<strong>[677306-38-6]indazole-4-carboxylic acid</strong></strong> (38 mg, 0.23 mmol), triethylamine (0.10 ml, 0.70 mmol), HOBT (38 mg, 0.28 mmol), and HBTU (110 mg, 0.28 mmol). The mixture was stirred at rt for 1 h, then quenched with pH 7 buffer and extracted with EtOAc. The layers were separated. The organic layer was successively washed with water and brine, then dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by flash chromatography with 50-100% EtOAc in hexane to afford the desired methyl ester (48 mg, 38% yield). This ester was dissolved in THF/water (2 ml/1 ml) and treated with LiOH.H2O (38 mg, 0.9 mmol) at 40 C. for 1 h. The mixture was quenched with 1N HCl and concentrated. The crude was purified by reverse phase HPLC to afford the desired product (HCl salt) (25 mg, 50% yield). MS m/e 522.0 (M+H+).

Reference： [1]Patent: US2012/238569,2012,A1 .Location in patent: Page/Page column 80

14
[ 677306-38-6 ]
4,5,6,7-tetrahydro-2H-indazol-3-amine dihydrochloride [ No CAS ]
(3-amino-4,5,6,7-tetrahydroindazol-2-yl)(1H-indazol-4-yl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
28%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 25℃;Inert atmosphere;	[146] Into a 50-mL round-bottom flask, was placed lH-<strong>[677306-38-6]indazole-4-carboxylic acid</strong> (3 g, 18.50 mmol, 1.20 equiv), 4,5,6,7-tetrahydro-2H-indazol-3-amine dihydrochloride (3.25 g, 15.47 mmol, 1.00 equiv), HOBT (3.75 g, 27.75 mmol, 1.80 equiv), EDCI (5.35 g, 27.91 mmol, 1.80 equiv), TEA (5.5 g, 54.35 mmol, 3.00 equiv), N,N-dimethylformamide (100 mL). The resulting solution was stirred overnight at 25 C. The reaction mixture was diluted with DCM (500 mL), washed with 0 (500 mL x 3) and brine (500 mL x 3) and dried with Na2SC>4. After filtration, the filtrate was concentrated under vacuum. The crude product was purified by Prep-HPLC with the following conditions (Analyse HPLC-SHIMADZU): Column, SunFire Prep C18, 19* 150mm; mobile phase, Phase A: water (0.1% FA), Phase B: CH3CN (10% CH3CN up to 40%); Detector, UV220&254nm. The collected fraction was lyophilized to give 1.2141 g (28%) of (3-amino-4,5,6,7-tetrahydroindazol-2-yl)(lH-indazol-4-yl)methanone (Example 47) as a light yellow solid. Rt= 37.5 min; MS (ES, m/z) [M+H]+: 282; 1HNMR(DMSO-t/6, 300MHz, />/wi): delta 13.32(s, 1H); 8.07(s, 1H); 7.81-7.75(m, 2H); 7.47-7.42(m, 1H); 6.47(s, 2H); 2.38-2.31(m, 4H); 1.26- 1.45(m, 4H).

Reference： [1]Patent: WO2017/205296,2017,A1 .Location in patent: Paragraph 146

15
[ 2740-83-2 ]
[ 677306-38-6 ]
[ 1194017-42-9 ]

Reference： [1]Patent: WO2009/134666,2009,A1

16
[ 677306-38-6 ]
[ 885271-63-6 ]

Reference： [1]Patent: WO2009/134666,2009,A1

17
[ 677306-38-6 ]
[ 1194019-84-5 ]

Reference： [1]Patent: WO2009/134666,2009,A1

18
[ 677306-38-6 ]
[ 1194017-77-0 ]

Reference： [1]Patent: WO2009/134666,2009,A1
[2]Patent: WO2009/134666,2009,A1

19
[ 677306-38-6 ]
[ 1194018-01-3 ]

Reference： [1]Patent: WO2009/134666,2009,A1

20
[ 677306-38-6 ]
[ 1194019-95-8 ]

Reference： [1]Patent: WO2009/134666,2009,A1
[2]Patent: WO2009/134666,2009,A1

21
[ 677306-38-6 ]
[ 1194019-15-2 ]

Reference： [1]Patent: WO2009/134666,2009,A1
[2]Patent: WO2009/134666,2009,A1

22
[ 677306-38-6 ]
[ 1194019-61-8 ]

Reference： [1]Patent: WO2009/134666,2009,A1

23
[ 677306-38-6 ]
[ 1194018-62-6 ]

Reference： [1]Patent: WO2009/134666,2009,A1
[2]Patent: WO2009/134666,2009,A1
[3]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 441 - 448

24
[ 677306-38-6 ]
[ 1194018-57-9 ]

Reference： [1]Patent: WO2009/134666,2009,A1
[2]Patent: WO2009/134666,2009,A1

25
[ 677306-38-6 ]
[ 1194019-97-0 ]

Reference： [1]Patent: WO2009/134666,2009,A1
[2]Patent: WO2009/134666,2009,A1

26
[ 677306-38-6 ]
[ 1194019-17-4 ]

Reference： [1]Patent: WO2009/134666,2009,A1
[2]Patent: WO2009/134666,2009,A1

27
[ 677306-38-6 ]
[ 1194017-72-5 ]

Reference： [1]Patent: WO2009/134666,2009,A1
[2]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 441 - 448

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[ 677306-38-6 ]
[ 1194018-56-8 ]

Reference： [1]Patent: WO2009/134666,2009,A1
[2]Patent: WO2009/134666,2009,A1

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[ 677306-38-6 ]
[ 1194019-93-6 ]

Reference： [1]Patent: WO2009/134666,2009,A1
[2]Patent: WO2009/134666,2009,A1

30
[ 677306-38-6 ]
[ 1194017-43-0 ]