114078-88-5|5-Bromo-1,2,3-triazine| Ambeed

CAS No. :	114078-88-5
Formula :	C₃H₂BrN₃
M.W :	159.97
SMILES Code :	BrC1=CN=NN=C1
MDL No. :	MFCD13193660
InChI Key :	LSBKXRBABHPHBW-UHFFFAOYSA-N
Pubchem ID :	13905235

Safety of [ 114078-88-5 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302
Precautionary Statements:	P280-P305+P351+P338

Computational Chemistry of [ 114078-88-5 ] Show Less

Physicochemical Properties

Num. heavy atoms	7
Num. arom. heavy atoms	6
Fraction Csp3	0.0
Num. rotatable bonds	0
Num. H-bond acceptors	3.0
Num. H-bond donors	0.0
Molar Refractivity	27.53
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	38.67 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.44
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	-0.01
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	0.63
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	0.3
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	1.49
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	0.77

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.46
Solubility	5.55 mg/ml ; 0.0347 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-0.35
Solubility	71.0 mg/ml ; 0.444 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-2.12
Solubility	1.21 mg/ml ; 0.00759 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	No
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-7.28 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	2.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	0.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	1.68

Application In Synthesis of [ 114078-88-5 ]

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

Downstream synthetic route of [ 114078-88-5 ]

[ 114078-88-5 ] Synthesis Path-Downstream 1~21

1
[ 3994-46-5 ]
[ 114078-88-5 ]
[ 114078-89-6 ]

References: [1]Chemical and pharmaceutical bulletin,1988,vol. 36,p. 3838 - 3848.
[2]Chemical and pharmaceutical bulletin,1987,vol. 35,p. 3952 - 3954.

2
[ 122481-11-2 ]
[ 114078-88-5 ]

Yield	Reaction Conditions	Operation in experiment
8.8 g	With sodium periodate; In dichloromethane; water; at 0℃; for 12.0h;	One step up the crude was added methylene chloride (200 mL) and water (76 mL), cooled to 0 , sodium periodate (29.4g, 137mmol) with stirring. After the addition was complete the reaction was stirred for 12 hours 0 . Warmed to 25 , liquid separation, the aqueous phase was extracted with dichloromethane (100mL × 3), the organic phases were combined, saturated brine (250mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated and the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10: 1) gave the title compound as a white solid (8.8g, yield 73.5% in two steps).
710 mg	With sodium periodate; In dichloromethane; water; at 20℃; for 16.0h;	To a solution of compound S2 (1 g, crude) in DCM (15 mL) and water (5 mL) was added NaIO4(2 g, 9.3 mmol). The reaction was stirred at room temperature for 16 hrs. The mixture was diluted with DCM and washed with water, brine, dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified by silica gel column (eluted with EtOAc/PE=1/5) to give the title compound (710 mg, 65.2% yield) as a purple solid.
	With sodium periodate; In dichloromethane; water; at 0℃; for 4.0h;	A solution of crude 4-bromopyrazol-l-amine (20.0 g, crude) in DCM (500 mL) and water (200 mL) was cooled to 0 C. To the solution was added NaI04 (52.8 g, 246.93 mmol). The resulting mixture was stirred at 0 C for 4 hrs and extracted with DCM (100 mL) for three times. The combined organic layer was washed with brine (100 mL), dried over anhydrous Na2S04 and concentrated in vacuo to give 5-bromotriazine (20.0 g) as brown solid, which was used in next step directly without any further purification

References: [1]Liebigs Annalen der Chemie,1993,p. 367 - 374.
[2]Chemical and pharmaceutical bulletin,1988,vol. 36,p. 3838 - 3848.
[3]Journal of the American Chemical Society,2011,vol. 133,p. 12285 - 12292.
[4]Patent: CN105884752,2016,A .Location in patent: Paragraph 0211; 0212; 0213.
[5]Patent: WO2017/35353,2017,A1 .Location in patent: Paragraph 0928.
[6]Patent: WO2018/83136,2018,A1 .Location in patent: Page/Page column 19; 20.

3
[ 7148-07-4 ]
[ 114078-88-5 ]
3-bromo-6,7-dihydro-5H-cyclopenta[b]pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
36%	In chloroform; at 45℃; for 1.0h;	To a solution of <strong>[114078-88-5]5-bromo-1,2,3-triazine</strong> (25 g, 156 mmol, 1.0 equiv) in CHCl3 (500 mL) was added 1-(cyclopent-1-en-1-yl)pyrrolidine (25.8 g, 188 mmol, 1.1 equiv). The mixture was stirred at 45 oC for 1 h, diluted with DCM (500 mL), washed with brine (300 mL) twice, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by silica gel chromatography (EA/PE, 10/90) to give 11 g (36%) of 3-bromo- 5H,6H,7H-cyclopenta[b]pyridine as a brown solid.
34.2%	In chloroform; at 0 - 45℃; for 0.833333h;	Weigh <strong>[114078-88-5]5-bromo-1,2,3-triazine</strong> (4.4g, 27.5mmol) was dissolved in chloroform (40 mL), and cooled to 0 deg.] C, was added 1-(cyclopentan-1-en-1-yl)pyrrolidine with stirring -1 After the addition, the reaction mixture was stirred at 0 C for 5 minutes, and raised to 45 C for 45 minutes. The crude product was purified by column chromatography on silica gel (petroleum ether: ethyl acetate = 5: 1 (1: 1) ) to give the title compound (1.86g, yield 34.2%).
34.3%	In chloroform; at 45℃; for 16.0h;	To a solution of compound S3 (400 mg, 2.5 mmol) in CHCl3(10 mL) was added 1-(cyclopent-1-en-1-yl)pyrrolidine (516 mg, 3.8 mmol). The reaction was stirred at 45 C. for 16 hrs. The reaction mixture was diluted with DCM and washed water, brine, dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified by silica gel column (eluted with EtOAc/PE=1/10) to give the title compound (170 mg, 34.3% yield) as a gray solid.

References: [1]Journal of the American Chemical Society,2011,vol. 133,p. 12285 - 12292.
[2]Patent: WO2019/144041,2019,A1 .Location in patent: Paragraph 0204.
[3]Patent: CN105884752,2016,A .Location in patent: Paragraph 0214; 0215; 0216.
[4]Patent: WO2017/35353,2017,A1 .Location in patent: Paragraph 0929.

4
[ 52313-50-5 ]
[ 114078-88-5 ]
[ 1240601-78-8 ]

References: [1]Journal of the American Chemical Society,2011,vol. 133,p. 12285 - 12292.

5
[ 1125-99-1 ]
[ 114078-88-5 ]
[ 82132-68-1 ]

References: [1]Journal of the American Chemical Society,2011,vol. 133,p. 12285 - 12292.

6
[ 75371-82-3 ]
[ 114078-88-5 ]
5-bromo-2-dibenzylamino-3-methylpyridine [ No CAS ]

References: [1]Journal of the American Chemical Society,2011,vol. 133,p. 12285 - 12292.

7
[ 2678-54-8 ]
[ 114078-88-5 ]
[ 55849-30-4 ]

References: [1]Journal of the American Chemical Society,2011,vol. 133,p. 12285 - 12292.

8
[ 114078-88-5 ]
[ 143-37-3 ]
[ 7752-78-5 ]

References: [1]Journal of the American Chemical Society,2011,vol. 133,p. 12285 - 12292.

9
[ 114078-88-5 ]
[ 4231-35-0 ]
[ 1220038-46-9 ]

References: [1]Journal of the American Chemical Society,2011,vol. 133,p. 12285 - 12292.

10
[ 114078-88-5 ]
[ 618-39-3 ]
[ 38696-20-7 ]

References: [1]Journal of the American Chemical Society,2011,vol. 133,p. 12285 - 12292.

11
C₂₂H₂₂N₂O [ No CAS ]
[ 114078-88-5 ]
(9-bromo-5a,6-dihydroindolo[4,3-fg]quinolin-4(5H)-yl)(phenyl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
3.1 mg	In chloroform; at 25℃; for 48.0h;	A solution of 12 (16.9 mg, 0.0609 mmol)and 4 A molecular sieves (85 mg) in CHCl3 (1.2 mL, 0.05 M, passedthrough basic alumina) was treated dropwise with pyrrolidine(22 mL, 0.30 mmol) at 25 C. After stirring for 10 h at room tem-perature, the mixture was ltered through a pad of Celite (10%MeOHeCH2Cl21% Et3N) and the solvent was removed under re-duced pressure. The crude enamine was dried under high vacuumfor 5 h. A solution of the enamine 13 in CHCl3 (0.31 mL, passedthrough basic alumina) was treated dropwise with <strong>[114078-88-5]5-bromo-1,2,3-triazine</strong> (20, 19.4 mg, 0.122 mmol) in CHCl3 (0.3 mL). The reactionmixture was stirred for 48 h at 25 C before the solvent was re-moved under reduced pressure. The residue was puried by pre-parative thin-layer chromatography (SiO2, 5% MeOHeCH2Cl2)toprovide 26 (3.1 mg, 13%) as a light tan solid: 1H NMR (500 MHz,CDCl3,50C) d 8.50 (d, J2.2 Hz, 1H), 8.12 (d, J2.2 Hz, 1H), 7.61 (d,J7.1 Hz, 2H), 7.44e7.55 (m, 3H), 7.10e7.36 (m, 2H), 4.51 (br s, 1H),3.90 (t, J10.7 Hz, 1H), 3.70e3.84 (m, 1H), 3.35 (dd, J15.4, 6.3 Hz,1H), 2.90 (t, J14.9 Hz,1H); 13C NMR (150 MHz, CDCl3,50C) d 168.9,155.0,149.0,141.9,136.4,133.0,132.6,130.7,130.6,129.3,128.7,127.4,119.5, 117.9, 117.2, 58.6, 36.6, 35.0; IR (lm) ymax 3345, 2923, 1642,1419,1384,1077, 787, 667 cm1; HRMS (ESI) m/z 391.0439 [(MH),C21H15BrN2O requires 391.0440]. The 1H and 13C NMR spectra of 26in CDCl3 at 25 C exhibit broadened peaks due to Bz rotamers.34

References: [1]Tetrahedron,2015,vol. 71,p. 5897 - 5905.

12
[ 45695-56-5 ]
[ 114078-88-5 ]
[ 400859-08-7 ]

Yield	Reaction Conditions	Operation in experiment
9.0 g	In 1,4-dioxane; at 0 - 30℃; for 2.0h;	To a solution of <strong>[114078-88-5]5-bromotriazine</strong> (20.0 g, crude) in 1,4-dioxane (600 mL) was added pyrimidine-2-carboxamidine (16.8 g, 137.53 mmol) at 0 C. After being stirred at 0 C for 1 hrs, the resulting mixture was warmed to 30 C and stirred at 30 C for 1 hr, and then filtered. The filtrate was concentrated in vacuo. The residue was diluted with H20 (500 mL) and extracted with DCM (500 mL) for three times. The combined organic layer was washed with brine (1.0 L), dried over anhydrous Na2S04 and concentrated in vacuo. The residue was purified on silica gel column (eluting with DCM/MeOH= 10/1, v:v) to give 5-bromo-2-pyrimidin-2-yl-pyrimidine (9.0 g) as yellow solid.

References: [1]Patent: WO2018/83136,2018,A1 .Location in patent: Page/Page column 20.

13
[ 14092-11-6 ]
[ 114078-88-5 ]
[ 51490-23-4 ]

Yield	Reaction Conditions	Operation in experiment
67%	In chloroform; at 0 - 45℃; for 0.75h;Molecular sieve;	Compound (M-21) (2.00 g, 12.5 mmol) was dissolved in chloroform (25.0 mL), 4A molecular sieve (400 mg,powder) was added, compound (M-22) (3.10 g, 18.8 mmol) was added at 0C, and the mixture was stirred at 0C for 5min. After stirring at 45C for 40 min, the mixture was allowed to cool to room temperature. The solvent was evaporatedunder reduced pressure, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate) togive compound (M-23) (yield 1.90 g, 67%)

References: [1]Patent: EP3351533,2018,A1 .Location in patent: Paragraph 0370; 0371.

14
[ 14092-11-6 ]
[ 114078-88-5 ]
C₁₀H₁₂BrN [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67%	In chloroform; at 0 - 45℃; for 0.75h;Molecular sieve;	Compound (M-21) (2.00 g, 12.5 mmol)Was dissolved in chloroform (25.0 mL)4 A molecular sieve (400 mg, powder)And the compound (M-22) (3.10 g, 18.8 mmol) was added at 0 C.,And the mixture was stirred at 0 C. for 5 minutes.After stirring at 45 C. for 40 minutes, it was allowed to cool to room temperature.The solvent was distilled off under reduced pressure,The residue was purified by silica gel column chromatography (n-hexane: ethyl acetate)Compound (M-23)(Yield 1.90 g, yield 67%).

References: [1]Patent: JP2018/145180,2018,A .Location in patent: Paragraph 0350; 0351; 0352.

15
ethyl 2-(ethoxy(imino)methyl)cyclobutanecarboxylate [ No CAS ]
[ 114078-88-5 ]
ethyl 2-(5-bromopyrimidin-2-yl)cyclobutanecarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In acetonitrile; at 20 - 80℃; for 24.0h;	To a solution of <strong>[114078-88-5]5-bromo-1,2,3-triazine</strong> (3.98 g, 24.88 mmol) in ACN (25 mE) was added ethyl 2-(ethoxy(imino)methyl)cyclobutanecarboxylate (8.40 g,42.20 mmol), and the reaction mixture was stirred at room temperature for 5 minutes before heated to 80 C. and stirred for 24 h. The resulting mixture was concentrated under vacuum. The residue was purified by a silica gel colunm chromatography, eluted with gradient 5%-25% EtOAc in petroleum ethet The fractions containing desired product were combined and concentrated under vacuum to afford ethyl 2-(5-bromopyrimidin-2-yl)cyclobutanecarboxylate. (ES, mlz): 285.0, 287.0 [M+H].

References: [1]Patent: US2018/354955,2018,A1 .Location in patent: Paragraph 0388.

16
[ 2075-45-8 ]
[ 114078-88-5 ]

Yield	Reaction Conditions	Operation in experiment
25 g		To a solution of 4-bromo-1H-pyrazole (50 g, 340 mmol, 1.0 equiv) in sodium hydroxide (3.7 N, 555 mL) was added (aminooxy)sulfonic acid (116 g, 1.0 mol, 3.0 equiv). The mixture was stirred for 30 min and extracted with DCM (500 mL). The organic layer was washed with brine (200 mL) twice, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and poured into DCM (400 mL) and water (200 mL). To the resulting solution was added NaIO4 (147 g, 685 mmol, 2.0 equiv) at 0 oC. The mixture was stirred overnight, diluted with DCM (500 mL), washed with brine (200 mL) twice, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to afford 25 g of 5- bromo-1,2,3-triazine as brown oil.

References: [1]Patent: WO2019/144041,2019,A1 .Location in patent: Paragraph 0203.

17
[ 614-27-7 ]
[ 114078-88-5 ]
5-bromo-2-phenylnicotinic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With potassium hydroxide; In acetonitrile; at 80℃; for 8.0h;Inert atmosphere;	In a 10 mL vacuum tube, add <strong>[114078-88-5]5-bromo-1,2,3-triazine</strong> 1a (15.9 mg, 0.10 mmol), methyl 3-oxo-3-phenylpropionate 3b (26.9 mg, 0.15 mmol) and KOH (2.8 mg, 0.05 mmol). Nitrogen was replaced three times, then 0.5 mL MeCN was added, and the reaction tube was placed at 80 C for 8 h. Follow the reaction by TLC, after terminating the reaction, add CH2Cl2 (3x10mL) for extraction, separate the organic phase, dry with Na2SO4, concentrate the organic phase in vacuo, and then obtain the target product 13c by column chromatography, yield (24.8mg, 85%)

References: [1]Patent: CN111004169,2020,A .Location in patent: Paragraph 0057-0059.

18
[ 105-45-3 ]
[ 114078-88-5 ]
methyl 5-bromo-2-methylnicotinate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With potassium hydroxide; In acetonitrile; at 80℃; for 8.0h;Inert atmosphere;	During the screening of reaction conditions, the effects of alkali on the reaction (label 1-9), solvent on the reaction (label 10-16), and temperature on the reaction (label 17-23) were investigated. Finally, KOH was determined as the best base, MeCN as the best solvent, and 80 as the best temperature. The reaction step of the above reference number 21 is as follows: In a 10 mL vacuum tube, add <strong>[114078-88-5]5-bromo-1,2,3-triazine</strong> 3a (15.9 mg, 0.10 mmol), methyl acetoacetate 1 b (17.4 mg, 0.15 mmol) and KOH (2.8 mg, 0.05 mmol). Nitrogen was replaced three times, then 0.5mL MeCN was added, and the reaction tube was placed at 80 C for 8h. Follow the reaction by TLC, after terminating the reaction, add MeCN (3x 10mL) for extraction, separate the organic phase, and dry with Na2SO4,The organic phase was concentrated in vacuo, and then subjected to column chromatography to obtain the target product 1c in a yield (19.7 mg, 86%).

References: [1]Patent: CN111004169,2020,A .Location in patent: Paragraph 0033-0046.

19
[ 114078-88-5 ]
[ 14227-95-3 ]
C₁₀H₁₂BrN₃O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With pyridine; In benzene; at 50℃; for 0.5h;Inert atmosphere; Sealed tube;	In a 10 mL dry sealed reaction tube, sequentially add <strong>[114078-88-5]5-bromo-1,2,3-triazine</strong> 1a (15.9 mg, 0.10 mmol), 1- (cyanoacetyl) pyrrolidine 4b (24.9 mg, 0.18 mmol) And pyridine (31.6 mg, 0.40 mmol). After nitrogen substitution three times, solvent benzene (1.0 mL) was added, and the sealed reaction tube was placed at 50 C for 0.5 h. The reaction was monitored by TLC. After the reaction was completed, it was extracted with dichloromethane (3 * 10 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated in vacuo. After column chromatography, the target product 12c (20.2 mg, 75%) was obtained.Test and characterize the product 12c, see Figures 2 to 4,The characterization results prove that 1-(cyanoacetyl)pyrrolidine 4b is the ketene imine structure formed by cyanomethyl group under alkaline conditions and reacts with <strong>[114078-88-5]5-bromo-1,2,3-triazine</strong> 1a, 1 -The carbonyl group of the amide in (cyanoacetyl)pyrrolidine 4b does not easily form an enol structure and reacts with <strong>[114078-88-5]5-bromo-1,2,3-triazine</strong> 1a.

References: [1]Patent: CN111004284,2020,A .Location in patent: Paragraph 0057-0059.

20
[ 2739-97-1 ]
[ 114078-88-5 ]
C₁₀H₈BrN₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With DBN; In 1,4-dioxane; at 70℃; for 4.0h;Inert atmosphere; Sealed tube;	In a 10 mL dry sealed reaction tube, add <strong>[114078-88-5]5-bromo-1,2,3-triazine</strong> 1a (15.9 mg, 0.10 mmol), DBN (37.3 mg, 0.30 mmol) in sequenceAnd 2-acetonitrile pyridine 6b (23.6 mg, 0.20 mmol). After nitrogen substitution three times, the solvent 1,4-dioxane (1.0 mL) was added, and the sealed reaction tube was placed at 70 C. for 4 h. The reaction was monitored by TLC. After the reaction was completed, it was extracted with dichloromethane (3 * 10 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated in vacuo to obtain the target product 27c. For the single crystal structure, see FIG. 1.

References: [1]Patent: CN111004284,2020,A .Location in patent: Paragraph 0075-0077.

21
[ 50586-62-4 ]
[ 114078-88-5 ]
C₉H₁₄BrN₂O₃P [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With DBN; In 1,4-dioxane; at 70℃;Inert atmosphere; Sealed tube;	Using the most conditional verification experiment, the reaction steps are: in a 10mL dry sealed reaction tube, add <strong>[114078-88-5]5-bromo-1,2,3-triazine</strong> 1a (15.9mg, 0.10mmol), DBN (37.3 mg, 0.30 mmol) and diethyl cyanomethyl phosphate 1b (35.4 mg, 0.20 mmol). After nitrogen substitution three times, the solvent 1,4-dioxane (1.0 mL) was added, and the sealed reaction tube was placed at 70 C to react. The reaction was monitored by TLC. After the reaction was completed, it was extracted with dichloromethane (3 * 10mL). The organic phase was dried over anhydrous sodium sulfate and concentrated in vacuo. After column chromatography, the target product 1c (24.6mg) was obtained. 80%.

References: [1]Patent: CN111004284,2020,A .Location in patent: Paragraph 0033-0046.

Historical Records

Technical Information

• Alkyl Halide Occurrence • General Reactivity • Grignard Reaction • Hiyama Cross-Coupling Reaction • Kinetics of Alkyl Halides • Kumada Cross-Coupling Reaction • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Dihalides • Stille Coupling • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling

Related Functional Groups of
[ 114078-88-5 ]

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4-Bromo-1H-pyrazole

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Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
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

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

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Product Details of [ 114078-88-5 ]

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Physicochemical Properties

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Medicinal Chemistry

Application In Synthesis of [ 114078-88-5 ]

[ 114078-88-5 ] Synthesis Path-Downstream 1~21

Related Products

Historical Records

Technical Information

Categories

Related Functional Groups of
[ 114078-88-5 ]

Bromides

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Molarity Calculator

Total Compounds Calculator

Dissolution Calculator

Alternative Products

Product Details of [ 114078-88-5 ]

Safety of [ 114078-88-5 ]

Computational Chemistry of [ 114078-88-5 ] Show Less

Physicochemical Properties

Lipophilicity

Water Solubility

Pharmacokinetics

Druglikeness

Medicinal Chemistry

Application In Synthesis of [ 114078-88-5 ]

[ 114078-88-5 ] Synthesis Path-Downstream 1~21

Related Products

Historical Records

Technical Information

Categories

Related Functional Groups of [ 114078-88-5 ]

Bromides

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Molarity Calculator

Total Compounds Calculator

Dissolution Calculator

Related Functional Groups of
[ 114078-88-5 ]