405224-22-8|5-Bromo-2-oxo-1,2-dihydropyridine-3-carbonitrile| Ambeed

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Quality Control of [ 405224-22-8 ] Purity: 95% SDS Specification

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Product Details of [ 405224-22-8 ]

CAS No. :	405224-22-8
Formula :	C₆H₃BrN₂O
M.W :	199.00
SMILES Code :	N#CC1C(=O)NC=C(Br)C=1
MDL No. :	MFCD13184828
InChI Key :	SWTLLSLCDHXNIU-UHFFFAOYSA-N
Pubchem ID :	7204870

Safety of [ 405224-22-8 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P264-P270-P271-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P330-P332+P313-P337+P313-P362-P403+P233-P405-P501

Computational Chemistry of [ 405224-22-8 ] Show Less

Physicochemical Properties

Num. heavy atoms	10
Num. arom. heavy atoms	0
Fraction Csp3	0.17
Num. rotatable bonds	0
Num. H-bond acceptors	3.0
Num. H-bond donors	0.0
Molar Refractivity	43.2
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	53.22 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	0.84
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	0.68
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	0.64
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.	0.23
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	1.66
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	0.81

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.5
Solubility	6.26 mg/ml ; 0.0315 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.	-1.37
Solubility	8.4 mg/ml ; 0.0422 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	-1.44
Solubility	7.31 mg/ml ; 0.0367 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.	-7.03 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	1.0
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)	3.57

Application In Synthesis of [ 405224-22-8 ]

* 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 [ 405224-22-8 ]

[ 405224-22-8 ] Synthesis Path-Downstream 1~35

1
[ 20577-27-9 ]
[ 405224-22-8 ]

Yield	Reaction Conditions	Operation in experiment
88%		Acetic acid (34 ml) was added to 2-oxo-1,2-dihydropyridine-3-carbonitrile (6.28 g, 0.052 mol) and the mixture was heated to 130C. When the solid was dissolved, bromine (12.5 g, 0.078 mol) was added slowly and stirred at the same temperature for 3 hours.After the reaction solution was cooled to room temperature, dichloromethane and water were added. The organic layer was separated and the aqueous layer was washed with dichloromethane. The organic layer was collected, washed with brine, dried over anhydrous sodium sulfate and concentrated to give the desired compound (9.11 g, 88% yield) as a yellow solid.
75%	With bromine; sodium acetate; In acetic acid; at 20.0℃; for 2.0h;	5-Bromo-2-oxo-1,2-dihydropyridine-3-carbonitrile(12) To a stirring solutionof compound 11 (50 mg, 0.42 mmol)and NaOAc (69 mg, 0.84 mmol) in 5 mL glacial AcOH at room temperature was addedBr2 (21.5 muL, 0.42 mmol) for 2 h. The mixture was concentrated invacuum to remove AcOH. Purification by chromatography (EA) provided compound 12 (69 mg, 75%) as a yellow solid. MP:216~217C. 1H NMR (400 MHz, CD3COCD3): delta 11.70 (s, 1H), 8.22 (d, J= 2.8 Hz, 1H), 8.05 (d, J = 2.8 Hz, 1H).5
	With bromine; In acetic acid; at 20.0℃; for 14.0h;	5-Bromo-2-oxo-1,2-dihydro-pyridine-3-carbonitrile Brornine (29 ml, 560 mmol) was added to a stirred solution of 2-oxo-1,2-dihydro-pyridine-3-carbonitrile (34 g, 280 mmol) in acetic acid (180 ml) at room temperature. After 14 hours the reaction mixture was concentrated in vacuo and the resulting oil was trituated with ethanol to afford the title compound as a solid. 1H NMR delta (d6 DMSO) 12.8 (brs, 1H), 8.4 (d, 1H), 8.1 (d, 1H).

References: [1]Patent: KR101936851,2019,B1 .Location in patent: Paragraph 0173; 0181-0184.
[2]Journal of Enzyme Inhibition and Medicinal Chemistry,2019,vol. 34,p. 1426 - 1438.
[3]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 3251 - 3255.
[4]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 6578 - 6581.
[5]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 1577 - 1580.
[6]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 5578 - 5585.
[7]Patent: US2004/19052,2004,A1 .Location in patent: Page/Page column 17.

2
[ 405224-22-8 ]
[ 405224-23-9 ]

Yield	Reaction Conditions	Operation in experiment
84%	With phosphorus pentachloride; In trichlorophosphate;Reflux;	5-Bromo-2-chloronicotinonitrile (13) Compound 12 (69 mg, 0.35 mmol) and PCl5(109 mg, 0.52 mmol) were refluxed in POCl3 (5 mL) overnight. Themixture was cooled to room temperature and added to ice water in drops slowly,basified with NaOH (4 M)to pH 8, and extracted with CH2Cl2 (3×30 mL). Thecombined extracts were washed with aqueous NaHCO3, brine, dried overanhydrous Na2SO4, and concentrated in vacuum.Purification by chromatography (PE/EA = 20:1) provided compound 13 (63 mg, 84percent) as a yellow solid. MP:138~139°C. 1H NMR (400 MHz, CDCl3): delta 8.66 (d, J = 2.4 Hz, 1H), 8.12 (d, J = 2.4 Hz,1H).6
	With phosphorus pentachloride; trichlorophosphate; for 3.0h;Heating / reflux;	5-Bromo-2-chloro-nicotinonitrile 5-Bromo-2-oxo-1,2 dihydro-pyridine-3-carbonitrile (33 g, 166 mmol) was added to a suspension of PCl5 (96.6 g, 464 mmol) in POCl3 (20 ml, 216 mmol). The mixture was stirred at reflux for 3 hours, cooled to room temperature and then poured slowly into ice/water. The resulting solid was fitered, washed with water, and dried in vacuo to afford the title compounid. 1H NMR delta (d6 DMSO) 8.7 (d, 1H), 8.1 (d, 1H).

References: [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 1577 - 1580.
[2]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 5578 - 5585.
[3]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 3251 - 3255.
[4]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 6578 - 6581.
[5]Patent: US2004/19052,2004,A1 .Location in patent: Page/Page column 17.
[6]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 3026 - 3035.

3
[ 405224-22-8 ]
[ 405224-24-0 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 1577 - 1580.
[2]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 5578 - 5585.

4
[ 405224-22-8 ]
N-(5-bromo-1H-pyrazolo[3,4-b]pyridin-3-yl)-methanesulfonamide [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 1577 - 1580.

5
[ 405224-22-8 ]
N-(5-bromo-1H-pyrazolo[3,4-b]pyridin-3-yl)-propionamide [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 1577 - 1580.

6
[ 405224-22-8 ]
N-(5-bromo-1H-pyrazolo[3,4-b]pyridin-3-yl)-isobutyramide [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 1577 - 1580.

7
[ 405224-22-8 ]
[ 405224-25-1 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 1577 - 1580.
[2]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 5578 - 5585.

8
[ 405224-22-8 ]
1-(5-bromo-1H-pyrazolo[3,4-b]pyridin-3-yl)-3-ethyl-urea [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 1577 - 1580.

9
[ 405224-22-8 ]
cyclopentanecarboxylic acid (5-bromo-1H-pyrazolo[3,4-b]pyridin-3-yl)-amide [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 1577 - 1580.

10
[ 405224-22-8 ]
MR⁽⁰³³⁾T₀₀₆₈₀ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 1577 - 1580.
[2]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 5578 - 5585.

11
[ 405224-22-8 ]
[ 557112-47-7 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 1577 - 1580.

12
[ 96-34-4 ]
[ 405224-22-8 ]
[ 1083168-85-7 ]

Yield	Reaction Conditions	Operation in experiment
74%	With potassium carbonate; In tetrahydrofuran; N,N-dimethyl-formamide; at 80.0℃; for 4.25h;	Z. Methyl 2-(3-cvano-2-oxo-5-(4A5,5-tetramethyl-l,3,2-dioxaborolan-2- vDpyridin- 1 (2H)-yl)acetate; Step a: 2-(5-Bromo-3-cyano-2-oxopyridin-l(2H)-yl)acetate; To 5-bromo-3-cyano-2(lH)-pyridinone (1.4 g, 7.0 mmol) and potassium carbonate (1.9 g, 1.3 mL, 14.1 mmol), TetaF (26.4 mL) and methyl chloroacetate (1.53 g, 1.2 mL, 14.1 mmol) were added. The reaction was stirred at 80 0C. The starting material didn't dissolve well in TetaF. After 3.5 hours, mainly staring material was observed. DMF (18 mL) was added and the starting material went into solution. The reaction was heated at 80 0C for 45 minutes. The desired mass was observed by LCMS. The reaction was filtered using ethyl acetate and the solvent was evaporated under reduced pressure. The crude product was separated by column chromatography on silica gel (0-100percent ethyl acetate in hexane) to yield methyl 2-(5-bromo-3-cyano-2-oxopyridin-l(2H)-yl)acetate as a yellow solid (1.42 g, 74percent). ESI-MS m/z calc. 271.07, found 271.3 (M+l)+. Retention time 0.59 minutes.

References: [1]Patent: WO2008/141119,2008,A2 .Location in patent: Page/Page column 98.

13
[ 405224-22-8 ]
[ 74-88-4 ]
[ 1126779-29-0 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; In N,N-dimethyl-formamide; for 2.0h;	Reference Example 10; 5-bromo-1-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile To a solution of <strong>[405224-22-8]5-bromo-2-oxo-1,2-dihydropyridine-3-carbonitrile</strong> (507 mg) in DMF (5 mL) were added cesium carbonate (1.66 g) and methyl iodide (0.19 mL), and the mixture was stirred at 0° C. for 2 hr. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by column chromatography (hexane-ethyl acetate) to give the title compound (317 mg) as a solid.1H-NMR (CDCl3) delta: 3.61 (3H, s), 7.69 (1H, d), 7.85 (1H, d).

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 7076 - 7080.
[2]Patent: US2009/270359,2009,A1 .Location in patent: Page/Page column 35-36.

14
[ 405224-22-8 ]
[ 1349798-29-3 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 7076 - 7080.

15
[ 405224-22-8 ]
[ 1346540-97-3 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 3251 - 3255.

16
[ 405224-22-8 ]
5-bromo-2-((trimethylsilyl)ethynyl)nicotinonitrile [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 3251 - 3255.

17
[ 74-89-5 ]
[ 405224-22-8 ]
5-bromo-2-(methylamino)nicotinonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54%	With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; 1,8-diazabicyclo[5.4.0]undec-7-ene; In acetonitrile; at 20.0℃; for 7.0h;	Method 1: To a solution of 5.-bromo.-2-oxo-1,2--dihydropyridine-3.-carbonitriie in acetonitrile (0.1 M) was added DBU (2.0 equiv.), BOP (1,3 equiv.) and methyl amine (2M solution, 4.0 equiv.). The solution was stirred at room temperature for 7 hrs, the volatiles were removed in vacuo. the residue was dissolved in ethyl acetate and washed with water (2x), sodium carbonate, washed with brine and dried over magnesium sulfate, Filtered, concentrated and purified via silica gel column chromatography eluting with ethyl acetate (25°/o50percent) in heptanes. The pure fractions were concentrated to yield 5-bromo2(methylamino) nicotinonitrile in 54 yield as a white solid. CMS (rn/z) (M±H) =211.9/213.9, Rt zr 0,72 mm,

References: [1]Patent: WO2016/38583,2016,A1 .Location in patent: Paragraph 00124.

18
[ 405224-22-8 ]
[ 1083168-86-8 ]

References: [1]Patent: WO2008/141119,2008,A2 .

19
[ 405224-22-8 ]
[ 1083167-61-6 ]

References: [1]Patent: WO2008/141119,2008,A2 .

20
[ 6602-54-6 ]
[ 405224-22-8 ]