[ CAS No. 529508-58-5 ]

Name: 529508-58-5|1-(3-Fluorobenzyl)-5-nitro-1H-indazole|95%
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Product Details of [ 529508-58-5 ]

CAS No. :	529508-58-5	MDL No. :	MFCD09909402
Formula :	C₁₄H₁₀FN₃O₂	Boiling Point :	447.697°C at 760 mmHg
Linear Structure Formula :	-	InChI Key :	-
M.W :	271.25	Pubchem ID :	21966490
Synonyms :

Computed Properties of [ 529508-58-5 ]

TPSA :Topological Polar Surface Area	63.6	H-Bond Acceptor Count :	4
XLogP3 :	3.1	H-Bond Donor Count :	0
SP3 :	0.07	Rotatable Bond Count :	2

Safety of [ 529508-58-5 ]

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 [ 529508-58-5 ]

Upstream synthesis route of [ 529508-58-5 ]
Downstream synthetic route of [ 529508-58-5 ]

[ 529508-58-5 ] Synthesis Path-Upstream 1~9

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Yield	Reaction Conditions	Operation in experiment
49%	With caesium carbonate In N,N-dimethyl-formamide at 70 - 80℃; for 1.25 h;	5-nitro indazole (1 equiv. ), cesium carbonate (1. 1 equiv. ) and DMF (5 volumes) were charged to a vessel. The mixture was heated to 70-80 °C and 3-fluoro benzyl bromide was added over 75 mins. The reaction was assayed by HPLC for completion (<2 AP of nitro indazole vs combined isomers) and then cooled to 20 °C. The salts were filtered and the cake was washed with DMF (2.7 volumes). The product was crystallized by charging water (1.35 to 1.45 volumes) between 15-21 °C. The crystal slurry was held for 4 h, crystals were filtered and washed with 2: 1 DMF : water mix (2.1 volumes), water (2 volumes) and finally 3: 1 cold ACN: water mix (1.5 volumes). The wet cake was dried <45 °C to LOD <1percent and the yield was about 49percent lH NMR (CDC13) otilde; 5.64 (s, 2H), 6. 87 (d, 1H, J = 9.4 Hz), 6.95 (m, 2H), 7.30 (m, 1H), 7.42 (d, 1H, J = 9.2 Hz), 8.23 (d of d, 1H, J = 10 Hz and 2 Hz), 8.26 (s, 1H), 8. 72 (d, lH, J = 2 Hz); MS: 272 (M+H) + ; HPLC Ret Time: 6.99 min (YMC ODS-A 3 um, 4.6 x 50 mm column, 10 min gradient, 2.5 mL/min).
49%	With caesium carbonate In N,N-dimethyl-formamide at 70 - 80℃; for 1.25 h;	5-nitro indazole (1 equiv. ), cesium carbonate (1. 1 equiv. ) and DMF (5 volumes) were charged to a vessel. The mixture was heated to 70-80 °C and 3-fluoro benzyl bromide was added over 75 mins. The reaction was assayed by HPLC for completion (<2 AP of nitro indazole vs combined isomers) and then cooled to 20 °C. The salts were filtered and the cake was washed with DMF (2.7 volumes). The product was crystallized by charging water (1.35 to 1.45 volumes) between 15-21 °C. The crystal slurry was held for 4 h, crystals were filtered and washed with 2: 1 DMF : water mix (2.1 volumes), water (2 volumes) and finally 3: 1 cold ACN: water mix (1.5 volumes). The wet cake was dried <45 °C to LOD <1percent and the yield was about 49percent lH NMR (CDC13) otilde; 5.64 (s, 2H), 6. 87 (d, 1H, J = 9.4 Hz), 6.95 (m, 2H), 7.30 (m, 1H), 7.42 (d, 1H, J = 9.2 Hz), 8.23 (d of d, 1H, J = 10 Hz and 2 Hz), 8.26 (s, 1H), 8. 72 (d, lH, J = 2 Hz); MS: 272 (M+H) + ; HPLC Ret Time: 6.99 min (YMC ODS-A 3 um, 4.6 x 50 mm column, 10 min gradient, 2.5 mL/min).

Reference： [1] Patent: WO2005/58245, 2005, A2, . Location in patent: Page/Page column 32-33
[2] Patent: WO2005/58245, 2005, A2, . Location in patent: Page/Page column 32-33
[3] Journal of Medicinal Chemistry, 2009, vol. 52, # 21, p. 6527 - 6530
[4] Patent: WO2012/182, 2012, A1, . Location in patent: Page/Page column 11
[5] Patent: WO2012/356, 2012, A1, . Location in patent: Page/Page column 10-11

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[ 884874-01-5 ]

Yield	Reaction Conditions	Operation in experiment
39%	With potassium carbonate In tetrahydrofuran for 3 h; Heating / reflux	5-Nitroindazol (10.0 g, 61.3 mmol) was dissolved in TηF (100 mL). Potassium carbonate (25.4 g, 184 mmol) and 3-fluorobenzylbromide (12.7 g, 67.4 mmol) were added, and the mixture was heated to reflux for 3 h. The solvent was removed in vacuo, and the residue was dissolved in ethyl acetate (150 mL) and extracted with water (200 mL). The aqueous layer was extracted twice with ethyl acetate (100 mL each). The combined organic layers were dried over sodium sulfate, and the solvent was removed in vacuo. The residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 3:1) to yield 6.55 g (39percent) of the title compound (less polar component) and 5.84 g (35percent) of the regioisomeric 2H-indazole derivative (more polar component).¹H-NMR (400 MHz, DMSOd₆): δ = 5.80 (s, 2H), 7.04-7.15 (m, 3H), 7.37 (dt, IH), 7.98 (d, IH), 8.25 (dd, IH), 8.48 (s, IH), 8.86 (d, IH).LC/MS (method 2): R, = 1.23 min; MS (ESIpos): m/z = 272 [M+H]⁺.
38%	With potassium carbonate In DMF (N,N-dimethyl-formamide) at 75℃; for 4 h;	A modified procedure from WO 99/35146, p. 61 WAS followed. 5-nitroindazole (3.915 g, 24 mmol) treated with potassium carbonate (3.65 g, 1.1 equiv. ), and 3-fluorobenzyl bromide (5 g, 1.1 equiv. ) in 41 ml of dry DMF under N2. Reaction mixture is stirred at 75 °C for 4 hours. The crude product (yellow solid, 5.536 g) is isolated as in the reference procedure. Acetone (26 ml) is added to the crude product, and the insoluble solids are filtered off. To filtered solution is added water dropwise (12 ml) upon which an oil forms. The mixture is store in freezer at-20 C for 15 min, upon which the oil solidifies and remains solid after warming to r. t. Chromatography of the solid (silica, 0-10percent ETOAC/HEXANES) afforded 2.49 g of high Rf material (1-H regioisomer, 9.2 mmol, 38percent), 0.7 g of the low Rf material. (2-H isomer, 11 percent) and mixed fractions (0.71 g, 3percent).
32%	With potassium carbonate In acetonitrile at 70℃; for 12 h;	5-nitroindazole (15 g, 92 mmol, 1 eq), 3-fluorobenzylbromide (14.7 mL, 119.5 mmol, 1.3 eq) and potassium carbonate 25.4 g (184 mmol, 2 equiv) were suspended in 150 mL acetonitrile. The reaction mixture was stirred at 70° C. for 12 h, and then allowed to cool to rt. The resultant solid was filtered and washed with CH₂Cl₂, and the filtrate concentrated in vacuo. The crude mixture of regioisomeric products was purified by column:chromatography (5:1 to 4:1 Hex/EtOAc), yielding 5-nitro-1-N-(3-fluorobenzyl)indazole (7.9 g, 32percent) and 5-nitro-2-N-(3-fluorobenzyl)indazole (9.2 g, 37percent) as yellow solids.

Reference： [1] Patent: WO2009/33581, 2009, A1, . Location in patent: Page/Page column 61
[2] Patent: WO2004/46101, 2004, A2, . Location in patent: Page 43
[3] Patent: US2010/298297, 2010, A1, . Location in patent: Page/Page column 14; 15

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Yield	Reaction Conditions	Operation in experiment
46%	Stage #1: With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 1 h; Stage #2: at 0 - 20℃; for 12 h;	Sodium hydride (NaH) 95percent (0.81 g, 34.1 mmol) was added to a solution of 5-nitro-lH- indazole Compound 4a (5.3 g, 32.5 mmol) in DMF (33 mL) at 0 ⁰C under nitrogen. The mixture was stirred for 1 hour at RT, then l-bromomethyl-3-fluoro-benzene Compound 4b(6.14 g, 32.5 mmol) was added dropwise at 0 ⁰C. After stirring at RT for 12 hours, the reaction mixture was partitioned between ethyl acetate and icy water. The organic layer was washed with water, brine, dried (Na₂SO₄), filtered and the solvent evaporated in vacuo to yield a crude solid. The crude solid was purified via flash chromatography (100percent dichloromethane) to yield l-(3-fluoro-benzyl)-5-nitro-lH-indazole Compound 4c (4.02 g, 46percent) as a solid. ¹H NMR (400 MHz, CDCl₃) δ 8.76-8.75 (IH, m), 8.27-8.23 (2H, m), 7.40-7.38 (IH, m), 7.33-2.27 (IH, m), 7.01-6.97 (2H, m), 6.89-6.86 (IH, m), 5.64 (2H, s); MS (ES⁺) m/z 272.1 (MH⁺).

Reference： [1] Patent: WO2006/118749, 2006, A1, . Location in patent: Page/Page column 96

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Yield	Reaction Conditions	Operation in experiment
38%	With potassium carbonate In N,N-dimethyl-formamide at 75℃; for 4 h;	Step A: 1-(3-Fluoro-benzyl)-5-nitro-1 H-indazole A modified procedure from WO 99/35146, p. 61was followed. 5-nitroindazole (3.915 g, 24 mmol) treated with potassium carbonate (3.65 g, 1.1 equiv.), and 3-fluorobenzyl bromide (5 g, 1.1 equiv.) in 41 ml of dry DMF under N₂. Reaction mixture is stirred at 75° C. for 4 hours. The crude product (yellow solid, 5.536 g) is isolated as in the reference procedure. Acetone (26 ml) is added to the crude product, and the insoluble solids are filtered off. To filtered solution is added water dropwise (12 ml) upon which an oil forms. The mixture is store in freezer at -20 C for 15 min, upon which the oil solidifies and remains solid after warming to r.t. Chromatography of the solid (silica, 0-10percent EtOAc/hexanes) afforded 2.49 g of high Rf material (1-H regioisomer, 9.2 mmol, 38percent), 0.7 g of the low Rf material (2-H isomer, 11percent) and mixed fractions (0.71 g, 3percent).

Reference： [1] Patent: US2005/101617, 2005, A1, . Location in patent: Page/Page column 12-13

5
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Yield	Reaction Conditions	Operation in experiment
32%	With potassium carbonate In acetonitrile at 70℃; for 12 h;	Preparation of 5-amino-l-,/V-(3-fluorobenzyl) indazole; 5-nitroindazole (15 g, 92 mmol, 1 eq), 3-fluorobenzylbromide (14.7 mL,119.5 mmol, 1.3 eq) and potassium carbonate 25.4 g (184 mmol, 2 equiv) were suspended in 150 mL acetonitrile. The reaction mixture was stirred at 70 °C for 12h, and then allowed to cool to rt. The resultant solid was filtered and washed with CH₂Cl₂, and the filtrate concentrated in vacuo. The crude mixture of regioisomeric products was purified by column chromatography (5: 1 to 4: 1 Hex/EtOAc), yielding 5-nitro-1-N-(3-fluorobenzyl) indazole (7.9 g, 32percent) and 5-nitro-2-N-(3-fluorobenzyl) indazole (9.2 g, 37percent) as yellow solids.5-nitro-1-N-(3-fluorobenzyl) indazole (7.9 g, 29.1 mmol, 1 equiv) and iron (8.13 g , 145.6 mmol, 5 equiv) were mixed in 200 mL acetic acid and 50 mL EtOAc, and were stirred at rt for 36 h. The reaction mixture was filtered through a pad of Celite.(R).. The filtrate was concentrated in vacuo to 10 mL volume. The contents were diluted with water (10 mL) and neutralized with saturated Na₂CO₃ solution. The solution was extracted with EtOAc (3 x 500 mL), the combined organic layers dried over MgSO₄, filtered, and concentrated in vacuo. The resulting crude material was purified by column chromatography eluting with hexanes/EtOAC (4: 1 to 3: 1) to give 5-amino-1-N-(3-fluorobenzyl) indazole (5.32 g, 76percent) as a light brown solid. ¹H-NMR (DMSO-d₆) δ 7.72 (s, 1H), 7.22-7.36 (m, 2H), 6.87-7.05 (m, 3H), 6.70-6.77 (m, 2H), 5.48 (s, 2H), 4.78 (br s, 2H); LCMS RT = 1.66 min; [M+H]⁺ = 242.2.

Reference： [1] Patent: WO2006/44524, 2006, A1, . Location in patent: Page/Page column 42-43

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[ 833474-48-9 ]

Yield	Reaction Conditions	Operation in experiment
32%	With potassium carbonate In acetonitrile at 70℃; for 12 h;	5-nitroindazole (15 g, 92 mmol, 1 eq), 3-fluorobenzylbromide (14.7 mL, 119.5 mmol, 1.3 eq) and potassium carbonate 25.4 g (184 mmol, 2 equiv) were suspended in 150 mL acetonitrile. The reaction mixture was stirred at 70 °C for 12h, and then allowed to cool to rt. The resultant solid was filtered and washed with CH2Cl2, and the filtrate concentrated in vacuo. The crude mixture of regioisomeric products was purified by column chromatography (5:1 to 4:1 Hex/EtOAc), yielding 5-nitro-l-N-(3-fluorobenzyl) indazole (7.9 g, 32percent) and 5-nitro-2-N-(3-fluorobenzyl) indazole (9.2 g, 37percent) as yellow solids. 5-nitro-l-N-(3-fluorobenzyl) indazole (7.9 g, 29.1 mmol, 1 equiv) and iron (8.13 g , 145.6 mmol, 5 equiv) were mixed in 200 mL acetic acid and 50 mL EtOAc, and were stirred at rt for 36 h. The reaction mixture was filtered through a pad of Celite.(R).. The filtrate was concentrated in vacuo to 10 mL volume. The contents were diluted with water (10 mL) and neutralized with saturated Na2CO3 solution. The solution was extracted with EtOAc (3 x 500 mL), the combined organic layers dried over MgSO4, filtered, and concentrated in vacuo. The resulting crude material was purified by column chromatography eluting with hexanes/EtOAC (4:1 to 3:1) to give 5-amino-l-N-(3- fluorobenzyl) indazole (5.32 g, 76percent) as a light brown solid. 1H-NMR (DMSO-O6) δ 7.72 (s, IH), 7.22-7.36 (m, 2H), 6.87-7.05 (m, 3H), 6.70-6.77 (m, 2H), 5.48 (s, 2H), 4.78 (br s, 2H); LCMS RT = 1.66 min; [M+H]+ = 242.2.

Reference： [1] Patent: WO2006/23843, 2006, A2, . Location in patent: Page/Page column 104-105

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Yield	Reaction Conditions	Operation in experiment
42%	With potassium carbonate In acetoneReflux	Step A: l-(3-fluorobenzyl)-5-nitro-lH-indazole (compound 16.1).[0157] A suspension of 5-nitrobenzoindazole (8.16 g, 50 mmol), 3-fluorobenzyl bromide (10.4 g, 55 mmol) and potassium carbonate (13.8 g, 100 mmol) in acetone (200 mL) was refluxed overnight. After reaction cooled to room temperature, the reaction mixture was diluted with dichloromethane (100 mL), filtered through silica gel (about 100 g), and rinsed with 1 :1 ethyl acetate : dichloromethane (about 100 mL). The residue after concentration was purified with column chromatography eluting with 0-30percent ethyl acetate in dichloromethane to give the title compound as a white crystalline solid (the first fraction, 5.69 g, 42percent). LCMS ESI(+) m/z: 272 (M+l).

Reference： [1] Patent: WO2011/2523, 2011, A1, . Location in patent: Page/Page column 63

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[ 202197-31-7 ]

Yield	Reaction Conditions	Operation in experiment
33%	With Ki; potassium carbonate In water; N,N-dimethyl-formamide	E. Preparation of 1-(3-Fluoro-benzyl)-1H-indazol-5-ylamine A mixture of 5-nitro-1H-indazole (8.15 gm, 50 mmole), m-fluoro-benzyl chloride (7.95 gm, 1.1 equiv), K₂CO₃ (7.59 gm, 1.1 equiv), and KI (8.47 gm, 1.02 equiv) in dry DMF (75 mL) was heated at 70° C. overnight. After cooling to RT, water (75 mL) was slowly added to give a precipitate that consisted of about a one to one mixture of isomers [HPLC Ret Time: 1.92 (1-substitued isomer vs. 2.03 (2-substituted isomer) YMC C18 S5 4.650 mm, 3 min gradient, 4 mL/min]. This was collected by filtration and washed with water. The solid was crystallized twice from acetone/water to afford the desired 1-(3-fluoro-benzyl)-5-nitro-1H-indazole (4.47 gm, 33percent). A suspension of this material (3.00 gm, 11.1) and 10percent Pd/C (3.00 gm) in EtOH (21 mL) was kept under an H₂ atmosphere (balloon) for 24 hr. The catalyst was removed by filtration and the solvent was evaporated to leave the product as a solid (2.4 gm, 90percent). ¹H NMR (CDCl₃): δ 3.61 (br s, 2H), 5.52 (s, 2H), 6.81-7.85 (m, 7H), 7.85 (s, 1H); MS: 242 (M+H)⁺; HPLC Ret Time: 1.03 min (YMC Xterra ODS S7, 3.050 mm column, 2 min gradient, 5 mL/min).

Reference： [1] Patent: US2003/186983, 2003, A1,

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Reference： [1] Chinese Chemical Letters, 2011, vol. 22, # 11, p. 1277 - 1280

[ 529508-58-5 ] Synthesis Path-Downstream 1~8

1
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Yield	Reaction Conditions	Operation in experiment
39%; 35%	With potassium carbonate; In tetrahydrofuran; for 3h;Heating / reflux;	5-Nitroindazol (10.0 g, 61.3 mmol) was dissolved in TetaF (100 mL). Potassium carbonate (25.4 g, 184 mmol) and 3-fluorobenzylbromide (12.7 g, 67.4 mmol) were added, and the mixture was heated to reflux for 3 h. The solvent was removed in vacuo, and the residue was dissolved in ethyl acetate (150 mL) and extracted with water (200 mL). The aqueous layer was extracted twice with ethyl acetate (100 mL each). The combined organic layers were dried over sodium sulfate, and the solvent was removed in vacuo. The residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 3:1) to yield 6.55 g (39%) of the title compound (less polar component) and 5.84 g (35%) of the regioisomeric 2H-indazole derivative (more polar component).1H-NMR (400 MHz, DMSOd6): delta = 5.80 (s, 2H), 7.04-7.15 (m, 3H), 7.37 (dt, IH), 7.98 (d, IH), 8.25 (dd, IH), 8.48 (s, IH), 8.86 (d, IH).LC/MS (method 2): R, = 1.23 min; MS (ESIpos): m/z = 272 [M+H]+.
38%; 11%	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 75℃; for 4h;	A modified procedure from WO 99/35146, p. 61 WAS followed. 5-nitroindazole (3.915 g, 24 mmol) treated with potassium carbonate (3.65 g, 1.1 equiv. ), and 3-fluorobenzyl bromide (5 g, 1.1 equiv. ) in 41 ml of dry DMF under N2. Reaction mixture is stirred at 75 C for 4 hours. The crude product (yellow solid, 5.536 g) is isolated as in the reference procedure. Acetone (26 ml) is added to the crude product, and the insoluble solids are filtered off. To filtered solution is added water dropwise (12 ml) upon which an oil forms. The mixture is store in freezer at-20 C for 15 min, upon which the oil solidifies and remains solid after warming to r. t. Chromatography of the solid (silica, 0-10% ETOAC/HEXANES) afforded 2.49 g of high Rf material (1-H regioisomer, 9.2 mmol, 38%), 0.7 g of the low Rf material. (2-H isomer, 11 %) and mixed fractions (0.71 g, 3%).
32%; 37%	With potassium carbonate; In acetonitrile; at 70℃; for 12h;	5-nitroindazole (15 g, 92 mmol, 1 eq), 3-fluorobenzylbromide (14.7 mL, 119.5 mmol, 1.3 eq) and potassium carbonate 25.4 g (184 mmol, 2 equiv) were suspended in 150 mL acetonitrile. The reaction mixture was stirred at 70 C. for 12 h, and then allowed to cool to rt. The resultant solid was filtered and washed with CH2Cl2, and the filtrate concentrated in vacuo. The crude mixture of regioisomeric products was purified by column:chromatography (5:1 to 4:1 Hex/EtOAc), yielding 5-nitro-1-N-(3-fluorobenzyl)indazole (7.9 g, 32%) and 5-nitro-2-N-(3-fluorobenzyl)indazole (9.2 g, 37%) as yellow solids.

Reference： [1]Patent: WO2009/33581,2009,A1 .Location in patent: Page/Page column 61
[2]Patent: WO2004/46101,2004,A2 .Location in patent: Page 43
[3]Patent: US2010/298297,2010,A1 .Location in patent: Page/Page column 14; 15

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[ 202197-31-7 ]

Yield	Reaction Conditions	Operation in experiment
97%	With hydrogen;5%-palladium/activated carbon; In methanol; for 2h;	A solution of Compound 4c (2.0 g, 7.37 mmol) in MeOH (60 mL) was added to 5% Pd/C (0.2 g) under nitrogen. The reaction mixture was stirred for 2 hours under hydrogen atmosphere and then filtered through celite. The filtrate was evaporated in vacuo to yield l-(3- fluoro-benzyl)-lH-indazol-5-ylamine Compound 4d (1.72 g, 97%) as a solid. 1H NMR (400 MHz, CDCl3) delta 7.84 (IH, d), 7.28-7.21 (IH, m), 7.13 (IH, d, J= 8.8 Hz), 9.96-6.90 (3H, m), 6.84-6.81 (2H, m), 5.52 (2H, s), 3.60 (2H, br s); MS (ES+) m/z 242.1 (MH+).
95.42%	With palladium 10% on activated carbon; hydrogen; In methanol; at 25℃; for 10h;	The compound <strong>[529508-58-5]1-(3-fluorobenzyl)-5-nitro-1H-indazole</strong> (17.2 g, 63.5 mmol) was added to methanol (600 mL).Then 10% palladium on carbon (1.72 g) was added to the above solution.After replacing H2 three times,The reaction was stirred at 25 C for 10.0 h. Filtering,The filter cake was washed with methanol (150 mL), the filtrate was combined and concentrated.14.6 g of a reddish brown solid were obtained in a yield: 95.42%.This solid was used in the next reaction without purification.
90.8%	With hydrogen;platinum on carbon; In ethanol; water; at 60℃; for 4h;	Follow modified procedure from WO 99/35146. 1- (3-FLUORO-BENZYL)-5-NITRO-LH-INDAZOLE (2.49 g, 9.2 mmol) is suspended in 40 ml absolute ETOH and Pt/C (5%, wet, 150 mg) is added. The reaction mixture is stirred and heated at 60 C under a hydrogen atmosphere (balloon). Roughly 4 hours into the reaction LC/MS reveals the formation of substantial amounts of product. The mixture is filtered through Celite and concentrated under reduced pressure. Yield: 2. 01 g (90. 8%) of a white solid.

90.8%	With hydrogen;platinum on carbon; In ethanol; at 60℃; for 4h;	Step B: 1-(3-Fluoro-benzyl)-1 H-indazol-5-ylamine Follow modified procedure from WO 99/35146. <strong>[529508-58-5]1-(3-Fluoro-benzyl)-5-nitro-1H-indazole</strong> (2.49 g, 9.2 mmol) is suspended in 40 ml absolute EtOH and Pt/C (5%, wet, 150 mg) is added. The reaction mixture is stirred and heated at 60 C. under a hydrogen atmosphere (balloon). Roughly 4 hours into the reaction LC/MS reveals the formation of substantial amounts of product. The mixture is filtered through Celite and concentrated under reduced pressure. Yield: 2.01 g (90.8%) of a white solid.
84%	With hydrogen; In tetrahydrofuran; at 30 - 40℃; under 775.743 Torr; for 1h;	Benzyl nitro indazole (1 equiv.) was charged to a hyrdogenator, THF (8 volumes) was added and hydrogenated atl5 psi between 30-40 C. The reaction mixture was held for-1 h (s. m. <3% by HPLC) cooled to 25 C, the catalyst was filtered and the mixture was washed with THF (0.9 volumes). The mixture was transferred to another vessel, rinsed again with THF (0.4 volumes) distilled to the desired volume (5.5 volumes) atmospherically, and heptane was added (15 volumes) between 47-60 C over lh. The slurry was cooled over 1. 5h to 18-23 C. The slurry was held for 1h, filtered and washed with THF/heptane (1: 4,10. 4 volumes) and dried in oven <45 C, (LOD <1%). yield was 84%. melting point = 130C. HPLC Ret Time: 9.09 min
76%	With iron; acetic acid; In ethyl acetate; at 20℃; for 36h;	5-nitroindazole (15 g, 92 mmol, 1 eq), 3-fluorobenzylbromide (14.7 mL, 119.5 mmol, 1.3 eq) and potassium carbonate 25.4 g (184 mmol, 2 equiv) were suspended in 150 mL acetonitrile. The reaction mixture was stirred at 70 C for 12h, and then allowed to cool to rt. The resultant solid was filtered and washed with CH2Cl2, and the filtrate concentrated in vacuo. The crude mixture of regioisomeric products was purified by column chromatography (5:1 to 4:1 Hex/EtOAc), yielding 5-nitro-l-N-(3-fluorobenzyl) indazole (7.9 g, 32%) and 5-nitro-2-N-(3-fluorobenzyl) indazole (9.2 g, 37%) as yellow solids. 5-nitro-l-N-(3-fluorobenzyl) indazole (7.9 g, 29.1 mmol, 1 equiv) and iron (8.13 g , 145.6 mmol, 5 equiv) were mixed in 200 mL acetic acid and 50 mL EtOAc, and were stirred at rt for 36 h. The reaction mixture was filtered through a pad of Celite. The filtrate was concentrated in vacuo to 10 mL volume. The contents were diluted with water (10 mL) and neutralized with saturated Na2CO3 solution. The solution was extracted with EtOAc (3 x 500 mL), the combined organic layers dried over MgSO4, filtered, and concentrated in vacuo. The resulting crude material was purified by column chromatography eluting with hexanes/EtOAC (4:1 to 3:1) to give 5-amino-l-N-(3- fluorobenzyl) indazole (5.32 g, 76%) as a light brown solid. 1H-NMR (DMSO-O6) delta 7.72 (s, IH), 7.22-7.36 (m, 2H), 6.87-7.05 (m, 3H), 6.70-6.77 (m, 2H), 5.48 (s, 2H), 4.78 (br s, 2H); LCMS RT = 1.66 min; [M+H]+ = 242.2.
76%	With iron; acetic acid; In ethyl acetate; at 20℃; for 36h;	5-nitroindazole (15 g, 92 mmol, 1 eq), 3-fluorobenzylbromide (14.7 mL,119.5 mmol, 1.3 eq) and potassium carbonate 25.4 g (184 mmol, 2 equiv) were suspended in 150 mL acetonitrile. The reaction mixture was stirred at 70 C for 12h, and then allowed to cool to rt. The resultant solid was filtered and washed with CH2Cl2, and the filtrate concentrated in vacuo. The crude mixture of regioisomeric products was purified by column chromatography (5: 1 to 4: 1 Hex/EtOAc), yielding 5-nitro-1-N-(3-fluorobenzyl) indazole (7.9 g, 32%) and 5-nitro-2-N-(3-fluorobenzyl) indazole (9.2 g, 37%) as yellow solids.5-nitro-1-N-(3-fluorobenzyl) indazole (7.9 g, 29.1 mmol, 1 equiv) and iron (8.13 g , 145.6 mmol, 5 equiv) were mixed in 200 mL acetic acid and 50 mL EtOAc, and were stirred at rt for 36 h. The reaction mixture was filtered through a pad of Celite. The filtrate was concentrated in vacuo to 10 mL volume. The contents were diluted with water (10 mL) and neutralized with saturated Na2CO3 solution. The solution was extracted with EtOAc (3 x 500 mL), the combined organic layers dried over MgSO4, filtered, and concentrated in vacuo. The resulting crude material was purified by column chromatography eluting with hexanes/EtOAC (4: 1 to 3: 1) to give 5-amino-1-N-(3-fluorobenzyl) indazole (5.32 g, 76%) as a light brown solid. 1H-NMR (DMSO-d6) delta 7.72 (s, 1H), 7.22-7.36 (m, 2H), 6.87-7.05 (m, 3H), 6.70-6.77 (m, 2H), 5.48 (s, 2H), 4.78 (br s, 2H); LCMS RT = 1.66 min; [M+H]+ = 242.2.
76%		<strong>[529508-58-5]5-nitro-1-N-(3-fluorobenzyl)indazole</strong> (7.9 g, 29.1 mmol, 1 equiv) and iron (8.13 g, 145.6 mmol, 5 equiv) were mixed in 200 mL acetic acid and 50 mL EtOAc, and were stirred at rt for 36 h. The reaction mixture was filtered through a pad of Celite. The filtrate was concentrated in vacuo to 10 mL volume. The contents were diluted with water (10 mL) and neutralized with saturated Na2CO3 solution. The solution was extracted with EtOAc (3×500 mL), the combined organic layers dried over MgSO4, filtered, and concentrated in vacuo. The resulting crude material was purified by column chromatography eluting with hexanes/EtOAC (4:1 to 3:1) to give 5-amino-1-N-(3-fluorobenzyl)indazole (5.32 g, 76%) as a light brown solid. 1H-NMR (DMSO-d6) delta 7.72 (s, 1H), 7.22-7.36 (m, 2H), 6.87-7.05 (m, 3H), 6.70-6.77 (m, 2H), 5.48 (s, 2H), 4.78 (br s, 2H); LCMS RT=1.66 min; [M+H]+=242.2.
	With hydrogen;palladium 10% on activated carbon; In methanol; for 14h;	Step B: l-(3-fluorobenzyl)-lH-indazol-5-amine (compound 16.2).[0158] A suspension of compound 16.1 (2.71 g, 10 mmol) and palladium 10% on carbon (1.Og, wet) in methanol (40 mL) was hydrogenated under a hydrogen balloon for 14 hours. The reaction mixture was then filtered through Celite (20 g), rinsed withdichloromethane/methanol (3/1), and concentrated to give the title compound as a white crystalline solid (2.40 g, 100%). The product is used without further purification. LCMS ESI(+) m/z: 242 (M+ 1).
	With hydrogen;Raney's nickel; In methanol; at 20℃;Inert atmosphere;	Under N2, Raney's nickel (0.53g, wet weight) was added to a solution of 1-b (5.3 g, 19.7mmol) in methanol (20 mL) and the mixture was degassed and stirred under hydrogen atmosphere at room temperature overnight. The catalyst was carefully filtered and the filtrate was concentrated in vacuum to give 1-c (4.65 g, 5.28 mmol).
	With hydrogen; In methanol; at 20℃;Inert atmosphere;	[050] Under N2; Raney's nickel (0.53 g, wet weight) was added to a solution of 1-b (5.3 g, 19.7 mmol) in methanol (20 mL) and the mixture was degassed and stirred under hydrogen atmosphere at room temperature overnight. The catalyst was carefully filtered and the filtrate was concentrated in vacuum to give 1-c (4.65 g, 19.3 mmol).

Reference： [1]Patent: WO2006/118749,2006,A1 .Location in patent: Page/Page column 96
[2]Patent: CN104744446,2019,B .Location in patent: Paragraph 0908; 0918-0919; 1489; 1496-1498
[3]Patent: WO2004/46101,2004,A2 .Location in patent: Page 44
[4]Patent: US2005/101617,2005,A1 .Location in patent: Page/Page column 13
[5]Patent: WO2005/58245,2005,A2 .Location in patent: Page/Page column 33
[6]Patent: WO2006/23843,2006,A2 .Location in patent: Page/Page column 104-105
[7]Patent: WO2006/44524,2006,A1 .Location in patent: Page/Page column 42-43
[8]Patent: US2010/298297,2010,A1 .Location in patent: Page/Page column 15
[9]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 1332 - 1336
[10]Journal of Medicinal Chemistry,2009,vol. 52,p. 6527 - 6530
[11]Patent: WO2011/2523,2011,A1 .Location in patent: Page/Page column 63-64
[12]Chinese Chemical Letters,2011,vol. 22,p. 1277 - 1280
[13]Patent: WO2012/182,2012,A1 .Location in patent: Page/Page column 11
[14]Patent: WO2012/356,2012,A1 .Location in patent: Page/Page column 11

3
[ 456-42-8 ]
[ 5401-94-5 ]
[ 529508-58-5 ]
[ 202197-31-7 ]

Yield	Reaction Conditions	Operation in experiment
33%; 90%	With Ki; potassium carbonate; In water; N,N-dimethyl-formamide;	E. Preparation of 1-(3-Fluoro-benzyl)-1H-indazol-5-ylamine A mixture of 5-nitro-1H-indazole (8.15 gm, 50 mmole), m-fluoro-benzyl chloride (7.95 gm, 1.1 equiv), K2CO3 (7.59 gm, 1.1 equiv), and KI (8.47 gm, 1.02 equiv) in dry DMF (75 mL) was heated at 70 C. overnight. After cooling to RT, water (75 mL) was slowly added to give a precipitate that consisted of about a one to one mixture of isomers [HPLC Ret Time: 1.92 (1-substitued isomer vs. 2.03 (2-substituted isomer) YMC C18 S5 4.650 mm, 3 min gradient, 4 mL/min]. This was collected by filtration and washed with water. The solid was crystallized twice from acetone/water to afford the desired 1-(3-fluoro-benzyl)-5-nitro-1H-indazole (4.47 gm, 33%). A suspension of this material (3.00 gm, 11.1) and 10% Pd/C (3.00 gm) in EtOH (21 mL) was kept under an H2 atmosphere (balloon) for 24 hr. The catalyst was removed by filtration and the solvent was evaporated to leave the product as a solid (2.4 gm, 90%). 1H NMR (CDCl3): delta 3.61 (br s, 2H), 5.52 (s, 2H), 6.81-7.85 (m, 7H), 7.85 (s, 1H); MS: 242 (M+H)+; HPLC Ret Time: 1.03 min (YMC Xterra ODS S7, 3.050 mm column, 2 min gradient, 5 mL/min).

Reference： [1]Patent: US2003/186983,2003,A1

4
[ 456-41-7 ]
[ 5401-94-5 ]
[ 529508-58-5 ]
5-nitro-2-N-(3-fluorobenzyl)indazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
32%; 37%	With potassium carbonate; In acetonitrile; at 70℃; for 12h;	Preparation of 5-amino-l-,/V-(3-fluorobenzyl) indazole; 5-nitroindazole (15 g, 92 mmol, 1 eq), 3-fluorobenzylbromide (14.7 mL,119.5 mmol, 1.3 eq) and potassium carbonate 25.4 g (184 mmol, 2 equiv) were suspended in 150 mL acetonitrile. The reaction mixture was stirred at 70 C for 12h, and then allowed to cool to rt. The resultant solid was filtered and washed with CH2Cl2, and the filtrate concentrated in vacuo. The crude mixture of regioisomeric products was purified by column chromatography (5: 1 to 4: 1 Hex/EtOAc), yielding 5-nitro-1-N-(3-fluorobenzyl) indazole (7.9 g, 32%) and 5-nitro-2-N-(3-fluorobenzyl) indazole (9.2 g, 37%) as yellow solids.5-nitro-1-N-(3-fluorobenzyl) indazole (7.9 g, 29.1 mmol, 1 equiv) and iron (8.13 g , 145.6 mmol, 5 equiv) were mixed in 200 mL acetic acid and 50 mL EtOAc, and were stirred at rt for 36 h. The reaction mixture was filtered through a pad of Celite. The filtrate was concentrated in vacuo to 10 mL volume. The contents were diluted with water (10 mL) and neutralized with saturated Na2CO3 solution. The solution was extracted with EtOAc (3 x 500 mL), the combined organic layers dried over MgSO4, filtered, and concentrated in vacuo. The resulting crude material was purified by column chromatography eluting with hexanes/EtOAC (4: 1 to 3: 1) to give 5-amino-1-N-(3-fluorobenzyl) indazole (5.32 g, 76%) as a light brown solid. 1H-NMR (DMSO-d6) delta 7.72 (s, 1H), 7.22-7.36 (m, 2H), 6.87-7.05 (m, 3H), 6.70-6.77 (m, 2H), 5.48 (s, 2H), 4.78 (br s, 2H); LCMS RT = 1.66 min; [M+H]+ = 242.2.

Reference： [1]Patent: WO2006/44524,2006,A1 .Location in patent: Page/Page column 42-43

5
[ 456-41-7 ]
[ 529508-58-5 ]

Yield	Reaction Conditions	Operation in experiment
46%		Sodium hydride (NaH) 95% (0.81 g, 34.1 mmol) was added to a solution of 5-nitro-lH- indazole Compound 4a (5.3 g, 32.5 mmol) in DMF (33 mL) at 0 0C under nitrogen. The mixture was stirred for 1 hour at RT, then l-bromomethyl-3-fluoro-benzene Compound 4b(6.14 g, 32.5 mmol) was added dropwise at 0 0C. After stirring at RT for 12 hours, the reaction mixture was partitioned between ethyl acetate and icy water. The organic layer was washed with water, brine, dried (Na2SO4), filtered and the solvent evaporated in vacuo to yield a crude solid. The crude solid was purified via flash chromatography (100% dichloromethane) to yield l-(3-fluoro-benzyl)-5-nitro-lH-indazole Compound 4c (4.02 g, 46%) as a solid. 1H NMR (400 MHz, CDCl3) delta 8.76-8.75 (IH, m), 8.27-8.23 (2H, m), 7.40-7.38 (IH, m), 7.33-2.27 (IH, m), 7.01-6.97 (2H, m), 6.89-6.86 (IH, m), 5.64 (2H, s); MS (ES+) m/z 272.1 (MH+).

Reference： [1]Patent: WO2006/118749,2006,A1 .Location in patent: Page/Page column 96

7
[ 456-41-7 ]
[ 5401-94-5 ]
[ 529508-58-5 ]
[ 833474-48-9 ]

Yield	Reaction Conditions	Operation in experiment
32%; 37%	With potassium carbonate; In acetonitrile; at 70℃; for 12h;	5-nitroindazole (15 g, 92 mmol, 1 eq), 3-fluorobenzylbromide (14.7 mL, 119.5 mmol, 1.3 eq) and potassium carbonate 25.4 g (184 mmol, 2 equiv) were suspended in 150 mL acetonitrile. The reaction mixture was stirred at 70 C for 12h, and then allowed to cool to rt. The resultant solid was filtered and washed with CH2Cl2, and the filtrate concentrated in vacuo. The crude mixture of regioisomeric products was purified by column chromatography (5:1 to 4:1 Hex/EtOAc), yielding 5-nitro-l-N-(3-fluorobenzyl) indazole (7.9 g, 32%) and 5-nitro-2-N-(3-fluorobenzyl) indazole (9.2 g, 37%) as yellow solids. 5-nitro-l-N-(3-fluorobenzyl) indazole (7.9 g, 29.1 mmol, 1 equiv) and iron (8.13 g , 145.6 mmol, 5 equiv) were mixed in 200 mL acetic acid and 50 mL EtOAc, and were stirred at rt for 36 h. The reaction mixture was filtered through a pad of Celite. The filtrate was concentrated in vacuo to 10 mL volume. The contents were diluted with water (10 mL) and neutralized with saturated Na2CO3 solution. The solution was extracted with EtOAc (3 x 500 mL), the combined organic layers dried over MgSO4, filtered, and concentrated in vacuo. The resulting crude material was purified by column chromatography eluting with hexanes/EtOAC (4:1 to 3:1) to give 5-amino-l-N-(3- fluorobenzyl) indazole (5.32 g, 76%) as a light brown solid. 1H-NMR (DMSO-O6) delta 7.72 (s, IH), 7.22-7.36 (m, 2H), 6.87-7.05 (m, 3H), 6.70-6.77 (m, 2H), 5.48 (s, 2H), 4.78 (br s, 2H); LCMS RT = 1.66 min; [M+H]+ = 242.2.

Reference： [1]Patent: WO2006/23843,2006,A2 .Location in patent: Page/Page column 104-105

8
[ 456-41-7 ]
[ 5401-94-5 ]
[ 529508-58-5 ]

Yield	Reaction Conditions	Operation in experiment
49%	With caesium carbonate; In N,N-dimethyl-formamide; at 70 - 80℃; for 1.25h;	5-nitro indazole (1 equiv. ), cesium carbonate (1. 1 equiv. ) and DMF (5 volumes) were charged to a vessel. The mixture was heated to 70-80 C and 3-fluoro benzyl bromide was added over 75 mins. The reaction was assayed by HPLC for completion (<2 AP of nitro indazole vs combined isomers) and then cooled to 20 C. The salts were filtered and the cake was washed with DMF (2.7 volumes). The product was crystallized by charging water (1.35 to 1.45 volumes) between 15-21 C. The crystal slurry was held for 4 h, crystals were filtered and washed with 2: 1 DMF : water mix (2.1 volumes), water (2 volumes) and finally 3: 1 cold ACN: water mix (1.5 volumes). The wet cake was dried <45 C to LOD <1% and the yield was about 49% lH NMR (CDC13) o 5.64 (s, 2H), 6. 87 (d, 1H, J = 9.4 Hz), 6.95 (m, 2H), 7.30 (m, 1H), 7.42 (d, 1H, J = 9.2 Hz), 8.23 (d of d, 1H, J = 10 Hz and 2 Hz), 8.26 (s, 1H), 8. 72 (d, lH, J = 2 Hz); MS: 272 (M+H) + ; HPLC Ret Time: 6.99 min (YMC ODS-A 3 um, 4.6 x 50 mm column, 10 min gradient, 2.5 mL/min).
41.1%		The compound 5-nitrocarbazole (30 g, 184.1 mmol) was dissolved in methyl ethyl ketone (700 mL).To the solution was added cesium carbonate (119 g, 386.0 mmol),After stirring at room temperature for 30 min,Slowly added m-fluorobenzyl bromide (38.04 g, 202.2 mmol),The temperature was raised to 85 C and reacted for 8.0 h. filter,The filter cake was washed with methyl ethyl ketone (100 mL), the organic phases were combined and concentrated.Obtained a brown solid and separated by column chromatography (eluent:Petroleum ether / dichloromethane (v / v) = 3 / 1),20.44 g of a pale yellow solid were obtained in a yield: 41.1%.
	With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 3h;	A mixture of 5-nitro-lH-indazole (1-a, 5 g, 30.65 mmol),l-(bromomethyl)-3-fluorobenzene (3.76 mL, 30.65 mmol) and potassium carbonate powder (4.66 g, 30.65 mmol) in DMF (3 mL) was stirred at 80C for 3 h and then poured into water (lOOmL). The precipitates were obtained by filtration and further purified by chromatography on silica gel (PE/EtOAc=3 : l) to give 1-2 (5.3 g, 19.7 mmol).

With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 3h;

Example 1: (3aR, 6aR)-N-(4-(l-(3-fluorobenzyl)-lH-indazol-5-ylamino)-7- methoxyquinazolin-6-yl)- 1 -methylhexahydropyrrolo [3 ,4-b]pyrrole-5( 1 H)-carboxamide[048] Compound 1 was prepared according to the following scheme. [049] A mixture of 5-nitro-lH-indazole (1-a, 5 g, 30.65 mmol),l-(bromomethyl)-3-fluorobenzene (3.76 mL, 30.65 mmol) and potassium carbonate powder (4.66 g, 30.65 mmol) in DMF (3 mL) was stirred at 80C for 3 h and then poured into water (100 mL). The precipitates were obtained by filtration and further purified by chromatography on silica gel (PE/EtOAc=3:l) to give 1-b (5.3 g, 19.7 mmol).

Reference： [1]Patent: WO2005/58245,2005,A2 .Location in patent: Page/Page column 32-33
[2]Patent: CN104744446,2019,B .Location in patent: Paragraph 0908; 0913-0916; 1489; 1492-1495
[3]Journal of Medicinal Chemistry,2009,vol. 52,p. 6527 - 6530
[4]Patent: WO2012/182,2012,A1 .Location in patent: Page/Page column 11
[5]Patent: WO2012/356,2012,A1 .Location in patent: Page/Page column 10-11

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P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
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. 529508-58-5 ]

Quality Control of [ 529508-58-5 ]

Related Doc. of [ 529508-58-5 ]

Product Details of [ 529508-58-5 ]

Computed Properties of [ 529508-58-5 ]

Safety of [ 529508-58-5 ]

Application In Synthesis of [ 529508-58-5 ]

[ 529508-58-5 ] Synthesis Path-Upstream 1~9

[ 529508-58-5 ] Synthesis Path-Downstream 1~8

Related Functional Groups of [ 529508-58-5 ]

Fluorinated Building Blocks

Nitroes

Aryls

Related Parent Nucleus of [ 529508-58-5 ]

Indazoles

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 529508-58-5 ]

Related Parent Nucleus of
[ 529508-58-5 ]