[ CAS No. 118863-62-0 ] {[proInfo.proName]}

Name: 118863-62-0|3-(4-Bromophenyl)-1H-[1,2,4]triazole|95%
Brand: Ambeed
SKU: A148346
Price: 11.0 USD
Availability: InStock
Rating: 92 (35 reviews)

,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

2D 3D

Structure of 118863-62-0 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 110K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 118863-62-0 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 118863-62-0 ]

SDS Specification

Alternatived Products of [ 118863-62-0 ]

Product Details of [ 118863-62-0 ]

CAS No. :	118863-62-0	MDL No. :	MFCD16659605
Formula :	C₈H₆BrN₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	XJSPWQRTWATLKK-UHFFFAOYSA-N
M.W :	224.06	Pubchem ID :	46948734
Synonyms :

Calculated chemistry of [ 118863-62-0 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	11
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	49.52
TPSA :	41.57 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) :	-6.01 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.36
Log Po/w (XLOGP3) :	2.34
Log Po/w (WLOGP) :	2.23
Log Po/w (MLOGP) :	2.08
Log Po/w (SILICOS-IT) :	2.75
Consensus Log Po/w :	2.15

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.32
Solubility :	0.108 mg/ml ; 0.000483 mol/l
Class :	Soluble
Log S (Ali) :	-2.85
Solubility :	0.315 mg/ml ; 0.0014 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.24
Solubility :	0.0129 mg/ml ; 0.0000577 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.7

Safety of [ 118863-62-0 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 118863-62-0 ]

* 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 [ 118863-62-0 ]
Downstream synthetic route of [ 118863-62-0 ]

[ 118863-62-0 ] Synthesis Path-Upstream 1~5

1
[ 1269646-41-4 ]
[ 118863-62-0 ]

Yield	Reaction Conditions	Operation in experiment
91%	With hydrazine hydrate; acetic acid In acetic acid at 90℃; for 3 h; Cooling with ice	Example 7 Preparation of 3-(4-bromophenyl)-1H-1,2,4-triazole (C4) (0172) (0173) (E)-4-Bromo-N-((dimethylamino)methylene)benzamide (C3) (17.2 g, 67.3 mmol) in acetic acid (35 mL) was cooled in an ice bath. Hydrazine monohydrate (6.50 mL, 104 mmol) was slowly added while stirring vigorously. A white solid began to form. The reaction was heated at 90° C. for 3 hours. The solution was cooled and poured into cold water (150 mL). The precipitate was filtered, washed with cold water, and dried under vacuum overnight to provide the title compound as a white solid (14.5 g, 91percent): mp>200° C. (dec.); ¹H NMR (400 MHz, DMSO-d₆) δ 14.24 (s, 1H), 8.52 (s, 1H), 8.04-7.91 (m, 2H), 7.75-7.63 (m, 2H); ESIMS m/z 224 ([M]⁺).
19.8 g	With acetic acid; hydrazine In acetic acid at 90℃; for 8 h;	4-Bromo benzamide (28.0 g, 0.140 mol) was suspended in 1,1-dimethoxy-N,N-dimethylmethanamine (50 mL, 420 mmol) and the solution was stirred and heated to 90° C. for 2 hours. The solution was then cooled to ambient temperature and diethyl ether (150 mL) was added. The solution was cooled to 0° C. overnight and filtered to give (E)-4-bromo-N-((dimethylamino)methylene)benzamide as a colorless solid (25.6 g). This material was then dissolved in acetic acid (50 mL) and hydrazine (3.50 g, 110 mmol) was added slowly (exotherm) to the stirred solution, which solidified. The mixture was heated to 90° C. and a stir bar was added. The solid slowly dissolved over 8 hours and was then cooled to ambient temperature and the solution was diluted with water (35 mL). The resulting white solid was filtered and dried in vacuo to furnish the title compound as a colorless solid (19.8 g, 88percent): ¹H NMR (400 MHz, DMSO-d₆) δ 13.91 (s, 1H), 8.51 (s, 1H), 8.01-7.93 (m, 2H), 7.73-7.67 (m, 2H; ESIMS m/z 224, 226 ([M+H]⁺).

Reference： [1] Patent: US2016/24027, 2016, A1, . Location in patent: Paragraph 0172-0173
[2] Patent: US2014/274688, 2014, A1, . Location in patent: Paragraph 0378; 0379

2
[ 1269646-41-4 ]
[ 118863-62-0 ]

Yield	Reaction Conditions	Operation in experiment
91%	With 2'-methyl-N-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)[1,1'-biphenyl]-3-carboxamide In acetic acid at 90℃; for 3 h; Cooling with ice	Example 14 Preparation of 3-(4-bromophenyl)-1H-1,2,4-triazole (C6) (E)-4-Bromo-N-((dimethylamino)methylene)benzamide (C5) (17.2 g, 67.3 mmol) in acetic acid (35 mL) was cooled in an ice bath. Hydrazine.monohydrate (6.50 mL, 104 mmol) was slowly added while stirring vigorously. A white solid began to form. The reaction was heated at 90° C. for 3 hours. The solution was cooled and poured into cold water (150 mL). The precipitate was filtered, washed with cold water, and dried under vacuum overnight to provide the title compound as a white solid (14.5 g, 91percent): mp>200° C. (dec.); ¹H NMR (400 MHz, DMSO-d₆) δ 14.24 (s, 1H), 8.52 (s, 1H), 8.04-7.91 (m, 2H), 7.75-7.63 (m, 2H); ESIMS m/z 224 ([M]⁺).

Reference： [1] Patent: US2016/24026, 2016, A1, . Location in patent: Paragraph 0230; 0231

3
[ 64128-11-6 ]
[ 624-84-0 ]
[ 118863-62-0 ]

Reference： [1] Journal of Medicinal Chemistry, 2015, vol. 58, # 13, p. 5323 - 5333
[2] Patent: WO2008/156726, 2008, A1, . Location in patent: Page/Page column 108-109

4
[ 698-67-9 ]
[ 118863-62-0 ]

Reference： [1] Patent: US2014/274688, 2014, A1,
[2] Patent: US2016/24026, 2016, A1,

5
[ 623-00-7 ]
[ 118863-62-0 ]

Reference： [1] Journal of Medicinal Chemistry, 2015, vol. 58, # 13, p. 5323 - 5333

[ 118863-62-0 ] Synthesis Path-Downstream 1~60

1
[ 118863-62-0 ]
[ 1160270-14-3 ]
C₂₈H₂₀F₃N₃O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In water; N,N-dimethyl-formamide; at 90℃; for 3h;	To a mixture of ethyl 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yi)-7-[4- (trifluoromethyl)phenyl]-2-naphthoate (50 mg, 0.106 mmol) from Example 3, Step 1, PdCl2CdPPf)-CH2Cl2 adduct (8.68 mg, 10.63 mumol), 3-(4-bromophenyl)-lH-l,2,4-triazole (35.7 mg, 0.159 mmol) under vacuum, was added DMF (2 mL) and 2 M potassium carbonate (0.159 ml, 0.319 mmol). The mixture was stirred under a nitrogen atmosphere at 90 0C for 3 h. The reaction was worked up by the addition of water, extracted with ethyl acetate, dried over Na2SO4, and evaporated. The residue was purified by Combiflash chromatography (0- 100%EtOAc/hexane) to afford the desired intermediate ester. The ester was dissolved in 2 mL of THF and ImL of MeOH and treated with 1 mL of 2 N KOH at rt for 3 h. The reaction was worked up by the addition of aqueous citric acid, extracted with ethyl acetate, dried over Na2SO4, and evaporated. The residue was purified by Combiflash chromatography (0-30% solvent A/DCM with solvent A being a mixture of concentrated ammonia and MeOH (1 :4)) to afford the desired 4-[4-(4H"-[l,2,4]triazol-3-yl)-phenyl]-7-(4-trifluoromethylphenyl)-2-naphthoic acid as a solid. MS: M+H(+ESI)= 460.0 and M-H(-ESI)= 458.0.

Reference： [1]Patent: WO2009/70873,2009,A1 .Location in patent: Page/Page column 75-76

2
[ 24424-99-5 ]
[ 118863-62-0 ]
tert-butyl 3-(4-bromophenyl)-4H-1,2,4-triazole-4-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In tetrahydrofuran; at 20℃;	Into a 1000 mL 3-necked flask, was placed a solution of ethyl 4- bromobenzenecarboximidoate (54.0 g, 237 mmol) in xylene (500 mL). To the mixture was added NH2NHCHO (14.22 g, 237 mmol). The resulting solution was heated to reflux overnight. The reaction mixture was cooled in an ice bath and filtered. The solid was washed with 700 mL <n="110"/>of petroleum ether and dried in an oven under reduced pressure to afford 3-(4-bromophenyl)-lH- 1,2,4-triazole (crude) as a white solid.Into a 500 mL 3-necked flask was placed a solution of 3-(4-bromophenyl)-lH- 1,2,4-triazole (2.24 g, 10.0 mmol) in TetaF (200 mL). To this was added TEA (1.10 g, 10.9 mmol). To the mixture was added BoC2O (2.39 g, 11.0 mmol). The resulting solution was stirred overnight at room temperature. The mixture was evaporated, and the residue was purified by chromatography (1 :20 EtOAc/PE) to provide tert-butyl 3-(4-bromophenyl)-4H-l,2,4-triazole- 4-carboxylate as a white solid.Into a 2000 mL 3-necked flask was placed a solution of tert-butyl 3-(4- bromophenyl)-4H-l ,2,4-triazole-4-carboxylate (80.0 g, 247 mmol) in CH2Cl2 (800 mL). To the mixture was added TFA (400 mL). The resulting solution was stirred at room temperature for 1 h. The reaction was evaporated to provide 3-(4-bromophenyl)-l//-l,2,4-triazole as a white solid. 1H NMR (300 MHz, DMSOd6) 8.52 (s, IH), 7.97 (d, 2H), 7.69 (d, 2H). Calc'd for C8H7BrN3 [M+H]+ 224, found 224.

Reference： [1]Patent: WO2008/156726,2008,A1 .Location in patent: Page/Page column 108-109

3
[ 64128-11-6 ]
[ 624-84-0 ]
[ 118863-62-0 ]

Yield	Reaction Conditions	Operation in experiment
	In xylene;Reflux;	Into a 1000 mL 3-necked flask, was placed a solution of ethyl 4- bromobenzenecarboximidoate (54.0 g, 237 mmol) in xylene (500 mL). To the mixture was added NH2NHCHO (14.22 g, 237 mmol). The resulting solution was heated to reflux overnight. The reaction mixture was cooled in an ice bath and filtered. The solid was washed with 700 mL <n="110"/>of petroleum ether and dried in an oven under reduced pressure to afford 3-(4-bromophenyl)-lH- 1,2,4-triazole (crude) as a white solid.Into a 500 mL 3-necked flask was placed a solution of 3-(4-bromophenyl)-lH- 1,2,4-triazole (2.24 g, 10.0 mmol) in TetaF (200 mL). To this was added TEA (1.10 g, 10.9 mmol). To the mixture was added BoC2O (2.39 g, 11.0 mmol). The resulting solution was stirred overnight at room temperature. The mixture was evaporated, and the residue was purified by chromatography (1 :20 EtOAc/PE) to provide tert-butyl 3-(4-bromophenyl)-4H-l,2,4-triazole- 4-carboxylate as a white solid.Into a 2000 mL 3-necked flask was placed a solution of tert-butyl 3-(4- bromophenyl)-4H-l ,2,4-triazole-4-carboxylate (80.0 g, 247 mmol) in CH2Cl2 (800 mL). To the mixture was added TFA (400 mL). The resulting solution was stirred at room temperature for 1 h. The reaction was evaporated to provide 3-(4-bromophenyl)-l//-l,2,4-triazole as a white solid. 1H NMR (300 MHz, DMSOd6) 8.52 (s, IH), 7.97 (d, 2H), 7.69 (d, 2H). Calc'd for C8H7BrN3 [M+H]+ 224, found 224.

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 5323 - 5333
[2]Patent: WO2008/156726,2008,A1 .Location in patent: Page/Page column 108-109

4
tert-butyl 3-(4-bromophenyl)-4H-1,2,4-triazole-4-carboxylate [ No CAS ]
[ 118863-62-0 ]

Yield	Reaction Conditions	Operation in experiment
	With trifluoroacetic acid; In dichloromethane; at 20℃; for 1h;	Into a 1000 mL 3-necked flask, was placed a solution of ethyl 4- bromobenzenecarboximidoate (54.0 g, 237 mmol) in xylene (500 mL). To the mixture was added NH2NHCHO (14.22 g, 237 mmol). The resulting solution was heated to reflux overnight. The reaction mixture was cooled in an ice bath and filtered. The solid was washed with 700 mL <n="110"/>of petroleum ether and dried in an oven under reduced pressure to afford 3-(4-bromophenyl)-lH- 1,2,4-triazole (crude) as a white solid.Into a 500 mL 3-necked flask was placed a solution of 3-(4-bromophenyl)-lH- 1,2,4-triazole (2.24 g, 10.0 mmol) in TetaF (200 mL). To this was added TEA (1.10 g, 10.9 mmol). To the mixture was added BoC2O (2.39 g, 11.0 mmol). The resulting solution was stirred overnight at room temperature. The mixture was evaporated, and the residue was purified by chromatography (1 :20 EtOAc/PE) to provide tert-butyl 3-(4-bromophenyl)-4H-l,2,4-triazole- 4-carboxylate as a white solid.Into a 2000 mL 3-necked flask was placed a solution of tert-butyl 3-(4- bromophenyl)-4H-l ,2,4-triazole-4-carboxylate (80.0 g, 247 mmol) in CH2Cl2 (800 mL). To the mixture was added TFA (400 mL). The resulting solution was stirred at room temperature for 1 h. The reaction was evaporated to provide 3-(4-bromophenyl)-l//-l,2,4-triazole as a white solid. 1H NMR (300 MHz, DMSOd6) 8.52 (s, IH), 7.97 (d, 2H), 7.69 (d, 2H). Calc'd for C8H7BrN3 [M+H]+ 224, found 224.

Reference： [1]Patent: WO2008/156726,2008,A1 .Location in patent: Page/Page column 108-109

5
[ 118863-62-0 ]
(Z)-1-(3-(2-isopropyl-5-methylphenyl)-4-oxothiazolidin-2-ylidene)-3-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenethyl)urea [ No CAS ]

Reference： [1]Patent: US2014/274688,2014,A1

6
[ 118863-62-0 ]
tert-butyl 4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenethylcarbamate [ No CAS ]

Reference： [1]Patent: US2014/274688,2014,A1
[2]Patent: US2016/24027,2016,A1
[3]Patent: US2016/24026,2016,A1
[4]Patent: WO2016/99929,2016,A1

7
[ 118863-62-0 ]
2-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)ethanamine [ No CAS ]

Reference： [1]Patent: US2014/274688,2014,A1
[2]Patent: WO2016/99929,2016,A1

8
[ 118863-62-0 ]
para-toluenesulfonic acid (Z)-1-(3-(2-isopropyl-5-methylphenyl)-4-oxothiazolidin-2-ylidene)-3-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenethyl)urea [ No CAS ]

Reference： [1]Patent: US2014/274688,2014,A1

9
[ 118863-62-0 ]
[ 103962-05-6 ]
3-(4-bromophenyl)-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52%	With copper(l) iodide; caesium carbonate; In dimethyl sulfoxide; at 100℃; for 72h;Inert atmosphere;	Example 8 Preparation of 3-(4-bromophenyl)-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole (C5) (0174) (0175) 3-(4-Bromophenyl)-1H-1,2,4-triazole (C4) (10.9 g, 48.5 mmol), copper(I) iodide (2.38 g, 12.5 mmol), and cesium carbonate (30.3 g, 93.0 mmol) in a round-bottomed flask was flushed with nitrogen. Dimethylsulfoxide (85 mL) was added, followed by 1-iodo-4-(trifluoromethoxy)benzene (13.2 g, 45.8 mmol). The reaction was degassed for 5 minutes, then heated at 100 C. for 3 days. The reaction was cooled to room temperature, diluted with ethyl acetate, and filtered through a plug of Celite rinsing with ethyl acetate. To the filtrate was added saturated ammonium chloride and stirred for 1.5 hours. The layers were separated and the aqueous layer was extracted with ethyl acetate (3×). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated onto Celite. Purification by flash column chromatography using 0-40% EtOAc/hexanes as eluent provided the title compound as an off-white solid (9.65 g, 52%): mp 109-112 C.; 1H NMR (400 MHz, CDCl3) delta 8.56 (s, 1H), 8.10-8.03 (m, 2H), 7.83-7.75 (m, 2H), 7.64-7.57 (m, 2H), 7.42-7.35 (m, 2H); ESIMS m/z 386 ([M+21-1 ]+).
52%	With copper(l) iodide; caesium carbonate; In dimethyl sulfoxide; at 100℃; for 72h;Inert atmosphere;	Example 15 Preparation of 3-(4-bromophenyl)-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole (C7) 3-(4-Bromophenyl)-1H-1,2,4-triazole (C6) (10.9 g, 48.5 mmol), copper(I) iodide (2.38 g, 12.5 mmol), and cesium carbonate (30.3 g, 93.0 mmol) in a round-bottomed flask was flushed with nitrogen. Dimethylsulfoxide (85 mL) was added, followed by 1-iodo-4-(trifluoromethoxy)benzene (13.2 g, 45.8 mmol). The reaction was degassed for 5 minutes, then heated at 100 C. for 3 days. The reaction was cooled to room temperature, diluted with ethyl acetate, and filtered through a plug of Celite rinsing with ethyl acetate. To the filtrate was added saturated ammonium chloride and stirred for 1.5 hours. The layers were separated and the aqueous layer was extracted with ethyl acetate (3*). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated onto Celite. Purification by flash column chromatography using 0-40% EtOAc/hexanes as eluent provided the title compound as an off-white solid (9.65 g, 52%): mp 109-112 C.; 1H NMR (400 MHz, CDCl3) delta 8.56 (s, 1H), 8.10-8.03 (m, 2H), 7.83-7.75 (m, 2H), 7.64-7.57 (m, 2H), 7.42-7.35 (m, 2H); ESIMS m/z 386 ([M+2H]+).
52%	With copper(l) iodide; caesium carbonate; In dimethyl sulfoxide; at 100℃; for 60h;Inert atmosphere;	A solution of 3-(4-bromophenyl)-lH-l,2,4-triazole (10.9 g, 48.5 mmol), l-iodo-4-(trifluoromethoxy)benzene (13.2 g, 45.8 mmol), copper(I) iodide (2.38 g, 12.5 mmol), and cesium carbonate (30.3 g, 93.0 mmol) in dimethylsulfoxide (85 mL) was degassed with nitrogen for 5 minutes. The mixture was heated at 100 C for 60 hours. After cooling, ethyl acetate (200 mL) was added and the mixture was filtered through Celite. The filtrate was added to a solution of saturated ammonium chloride (200 mL) and stirred for one and a half hours. The layers were separated and the aqueous layer was extracted with ethyl acetate (3 x 100 mL). The combined organic extracts were dried over anhydrous magnesium sulfate, filtered, and adsorbed onto Celite. Purification by flash column chromatography using 0-40% ethyl acetate/hexanes as eluent provided the title molecule as an off-white solid (9.65 g, 52%) : mp 109-112 C; XH NMR (400 MHz, CDCI3) delta 8.56 (s, 1H), 8.10-8.03 (m, 2H), 7.83-7.75 (m, 2H), 7.64-7.57 (m, 2H), 7.42-7.35 (m, 2H); ESIMS m/z 384 ([M + H]+).

50%

With copper(l) iodide; 8-quinolinol; caesium carbonate; In water; N,N-dimethyl-formamide; at 140℃; for 8h;

To a solution of 1-iodo-4-(trifluoromethoxy)benzene (15.0 g, 52.0 mmol) in dimethylformamide (90 mL) and water (10 mL) was added <strong>[118863-62-0]3-(4-bromophenyl)-1H-1,2,4-triazole</strong> (C51) (11.0 g, 49.0 mmol), cesium carbonate (34.0 g, 104 mmol), copper(I) iodide (2.80 g, 14.7 mmol), and 8-hydroxyquinoline (2.20 g, 15.0 mmol), and the solution was heated at 140 C. for 8 hours. The cooled solution was decanted from a layer of solid, diluted with a ammonium hydroxide (1N, 100 mL) solution, and extracted with of diethyl ether (2*100 mL). The combined organic layer was dried and concentrated, and the brown solid was eluted through a short silica gel column using 20% ethyl acetate/hexanes as eluent to give the title compound as a light tan solid (9.50 g, 50%): mp 111-113 C., 1H NMR (400 MHz, CDCl3) delta 8.56 (s, 1H), 8.07 (d, J=8.6 Hz, 2H), 7.79 (d, J=8.8 Hz, 2H), 7.62 (d, J=8.6 Hz, 2H), 7.39 (d, J=8.8 Hz, 2H); ESIMS m/z 384 ([M+H]+).

Reference： [1]Patent: US2016/24027,2016,A1 .Location in patent: Paragraph 0174-0175
[2]Patent: US2016/24026,2016,A1 .Location in patent: Paragraph 0232; 0233
[3]Patent: WO2016/99929,2016,A1 .Location in patent: Page/Page column 87; 88
[4]Patent: US2014/274688,2014,A1 .Location in patent: Paragraph 0380; 0381

10
[ 698-67-9 ]
[ 118863-62-0 ]

Reference： [1]Patent: US2014/274688,2014,A1
[2]Patent: US2016/24026,2016,A1
[3]Patent: WO2019/180646,2019,A1
[4]Patent: WO2019/180644,2019,A1
[5]Journal of the American Chemical Society,2020,vol. 142,p. 8270 - 8280

11
[ 1269646-41-4 ]
[ 118863-62-0 ]

Yield	Reaction Conditions	Operation in experiment
100%	With hydrazine hydrate; acetic acid; at 90℃; for 2h;	1.5 g of (£)-4-bromo-/V-((dimethylamino)methylene)benzamide prepared in Step 1 and 0.3 mL of hydrazine hydrate were dissolved in 15.0 mL acetic acid, and the resulting solution was stirred at 90C for 2 hours. The reaction mixture was cooled to room temperature and then 30.0 mL diethylether was added thereto. The reaction mixture thus obtained was stirred at room temperature for 1 hour. The resulting reaction mixture was additionally stirred at 0 C for 1 hour to give a solid. The resulting solid was filtered and dried to obtain 1.57 g of the title compound as a yellow solid (yield: 100.0%). 'H-NMR (CDCb, 400MHz) d 8.35(t, 1H), 7.80(d, 2H), 3.96(s, 3H), 3.83(d, 2H), 2T5-2. lO(m, 1H), l .06(d, 6H)
100%	With hydrazine hydrate; acetic acid; at 90℃; for 2h;	1.5 g of (E)-4-bromo-N-((dimethylamino)methylene)benzamide prepared in Step 1 and 0.3 mL of hydrazine hydrate were dissolved in 15.0 mL acetic acid, and the resulting solution was stirred at 90C for 2 hours. The reaction mixture was cooled to room temperature and then 30 mL diethylether was added thereto. The resulting reaction mixture was stirred at room temperature for 1 hour and then additionally stirred at 0C for 1 hour to give crystals. The resulting crystals were filtered and dried to obtain 1.57 g of the title compound as a yellow solid (yield: 100.0%). 1H-NMR (DMSO-de, 400 MHz) d l4.23(s, 1H), 8.5 l(s, 1H), 7.96(d, 2H), 7.69(d, 2H)
91%	With hydrazine hydrate; acetic acid; In acetic acid; at 90℃; for 3h;Cooling with ice;	Example 7 Preparation of 3-(4-bromophenyl)-1H-1,2,4-triazole (C4) (0172) (0173) (E)-4-Bromo-N-((dimethylamino)methylene)benzamide (C3) (17.2 g, 67.3 mmol) in acetic acid (35 mL) was cooled in an ice bath. Hydrazine monohydrate (6.50 mL, 104 mmol) was slowly added while stirring vigorously. A white solid began to form. The reaction was heated at 90 C. for 3 hours. The solution was cooled and poured into cold water (150 mL). The precipitate was filtered, washed with cold water, and dried under vacuum overnight to provide the title compound as a white solid (14.5 g, 91%): mp>200 C. (dec.); 1H NMR (400 MHz, DMSO-d6) delta 14.24 (s, 1H), 8.52 (s, 1H), 8.04-7.91 (m, 2H), 7.75-7.63 (m, 2H); ESIMS m/z 224 ([M]+).

19.8 g

With acetic acid; hydrazine; In acetic acid; at 90℃; for 8h;

4-Bromo benzamide (28.0 g, 0.140 mol) was suspended in 1,1-dimethoxy-N,N-dimethylmethanamine (50 mL, 420 mmol) and the solution was stirred and heated to 90 C. for 2 hours. The solution was then cooled to ambient temperature and diethyl ether (150 mL) was added. The solution was cooled to 0 C. overnight and filtered to give (E)-4-bromo-N-((dimethylamino)methylene)benzamide as a colorless solid (25.6 g). This material was then dissolved in acetic acid (50 mL) and hydrazine (3.50 g, 110 mmol) was added slowly (exotherm) to the stirred solution, which solidified. The mixture was heated to 90 C. and a stir bar was added. The solid slowly dissolved over 8 hours and was then cooled to ambient temperature and the solution was diluted with water (35 mL). The resulting white solid was filtered and dried in vacuo to furnish the title compound as a colorless solid (19.8 g, 88%): 1H NMR (400 MHz, DMSO-d6) delta 13.91 (s, 1H), 8.51 (s, 1H), 8.01-7.93 (m, 2H), 7.73-7.67 (m, 2H; ESIMS m/z 224, 226 ([M+H]+).

Reference： [1]Patent: WO2019/180646,2019,A1 .Location in patent: Paragraph 0195-0196
[2]Patent: WO2019/180644,2019,A1 .Location in patent: Paragraph 0227; 0230
[3]Patent: US2016/24027,2016,A1 .Location in patent: Paragraph 0172-0173
[4]Patent: US2014/274688,2014,A1 .Location in patent: Paragraph 0378; 0379

12
[ 623-00-7 ]
[ 118863-62-0 ]