60159-37-7|1-(4-Chloropyridine-2-yl)ethanone| Ambeed

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Quality Control of [ 60159-37-7 ] Purity: 97% SDS Specification

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Product Details of [ 60159-37-7 ]

CAS No. :	60159-37-7
Formula :	C₇H₆ClNO
M.W :	155.58
SMILES Code :	CC(C1=NC=CC(Cl)=C1)=O
MDL No. :	MFCD10697662
InChI Key :	BHKULLGEGMMZQD-UHFFFAOYSA-N
Pubchem ID :	13011986

Safety of [ 60159-37-7 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H332-H335
Precautionary Statements:	P261-P280-P305+P351+P338

Computational Chemistry of [ 60159-37-7 ] Show Less

Physicochemical Properties

Num. heavy atoms	10
Num. arom. heavy atoms	6
Fraction Csp3	0.14
Num. rotatable bonds	1
Num. H-bond acceptors	2.0
Num. H-bond donors	0.0
Molar Refractivity	39.44
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	29.96 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.8
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	1.5
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.94
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.	0.73
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	2.29
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.65

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.13
Solubility	1.16 mg/ml ; 0.00745 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-1.74
Solubility	2.85 mg/ml ; 0.0183 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	-2.96
Solubility	0.17 mg/ml ; 0.00109 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	Yes
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.	-6.18 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)	1.26

Application In Synthesis of [ 60159-37-7 ]

* 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 [ 60159-37-7 ]

[ 60159-37-7 ] Synthesis Path-Downstream 1~35

1
[ 60159-37-7 ]
[ 13325-10-5 ]
C₁₁H₁₇ClN₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%		4-Amino-l-butanol (0.13 ml, 0.0014 mol) was added at room temperature to a mixture of l-(4-chloro-2-pyridinyl)- ethanone (200 mg, 0.0013 mol), pαrø-toluene sulfonic acid (123 mg, 0.00065 mol), and 3A molecular sieves in MeOH (4 ml). The mixture was stirred 6 hours at room temperature, cooled down to O0C, and sodium borohydride (98 mg, 0.0026 mol) was slowly added. The mixture was stirred at room temperature for 18 hours. Molecular sieves were filtered off, and the mixture was poured out into water and the solvent was evaporated. The aqueous layer was basified with a saturated solution of sodium hydrogen carbonate, and extracted 3 times with DCM. The organic layer was separated, washed with brine, dried (MgSO4), filtered, and the solvent was evaporated. The residue was purified by column chromatography over silica gel (40-63 μm) (eluent: DCM/MeOH 95/5). The pure fractions were collected and the solvent was evaporated, yielding 269 mg (91%) of intermediate 20 as a yellow oil.

References: [1]Patent: WO2006/32631,2006,A1 .Location in patent: Page/Page column 46.

2
[ 60159-37-7 ]
[ 121638-26-4 ]

References: [1]Tetrahedron Asymmetry,2005,vol. 16,p. 3427 - 3435.

3
[ 19235-89-3 ]
[ 917-64-6 ]
[ 60159-37-7 ]

Yield	Reaction Conditions	Operation in experiment
76%		Step A Nitrile I (60 g, 0.42 mol) is dissolved in THF (1000 ml) in a 2 l three-necked flask fitted with stirrer and thermometer under an N2 protective-gas atmosphere and cooled to 0 C. by means of an ice bath. Commercially available MeMgl (200 ml of a 3 M solution in THF, 0.6 mmol) is slowly added over the course of about 45 min. A clear, dark solution initially forms. The dropwise addition rate of the MeMgl addition is adjusted so that the solution temperature in the reaction vessel is between 0-10 C. When all the Grignard reagent has been added, a green suspension is obtained, which is stirred at 0 C. for a further 2 h. The reaction mixture is then added to ice-water (1500 ml). 2 M HCl is added until the reaction mixture has an approx. pH2. The mixture is stirred for a further 15 min. and then extracted a number of times (addition of EtOAc and water). The combined organic phases are washed with aqueous saturated sodium chloride solution and dried using Na2SO4. All the solvents are removed by distillation under reduced pressure in a rotary evaporator, giving 66 g of yellow-brown oil as crude product. The crude product is purified by means of column chromatography (800 g of Si60, MTBE). The suitable fractions (characterised by TLC analysis) are combined. Removal of the solvents gives ketone II (51 g, 0.32 mol, 76% yield) as clear dark oil. LC-MS: tR=1.829 min (UV=220 nm), tR=1.842 min. (TIC, with [M+H]+=156); 1H NMR (300 MHz, CDCl3) δ 8.58 (d, 1H), 8.03 (dd, J=2.1, 0.4, 1H), 7.47 (dd, J=5.2, 2.1, 1H), 2.71 (d, J=3.2, 3H).

References: [1]Tetrahedron Asymmetry,2006,vol. 17,p. 1007 - 1016.
[2]Patent: US2012/220587,2012,A1 .Location in patent: Page/Page column 19.
[3]Tetrahedron Asymmetry,2005,vol. 16,p. 3427 - 3435.

4
[ 60159-37-7 ]
[ 872036-41-4 ]

References: [1]Tetrahedron Asymmetry,2006,vol. 17,p. 1007 - 1016.

5
[ 60159-37-7 ]
(R)-(+)-4-chloro-2-(1-hydroxyethyl)pyridine [ No CAS ]

References: [1]Tetrahedron Asymmetry,2006,vol. 17,p. 1007 - 1016.

6
[ 60159-37-7 ]
[ 124-40-3 ]
[ 896139-39-2 ]

References: [1]Tetrahedron Asymmetry,2006,vol. 17,p. 1007 - 1016.
[2]Journal of Medicinal Chemistry,2021,vol. 64,p. 2024 - 2045.

7
[ 60159-37-7 ]
[ 872036-49-2 ]

References: [1]Tetrahedron Asymmetry,2006,vol. 17,p. 1007 - 1016.
[2]Tetrahedron Asymmetry,2006,vol. 17,p. 1007 - 1016.

8
[ 60159-37-7 ]
[ 896139-43-8 ]

References: [1]Tetrahedron Asymmetry,2006,vol. 17,p. 1007 - 1016.
[2]Tetrahedron Asymmetry,2006,vol. 17,p. 1007 - 1016.

9
[ 60159-37-7 ]
[ 896139-48-3 ]

References: [1]Tetrahedron Asymmetry,2006,vol. 17,p. 1007 - 1016.
[2]Tetrahedron Asymmetry,2006,vol. 17,p. 1007 - 1016.

10
[ 60159-37-7 ]
4-Dimethylamino-2-((S)-1-methoxy-ethyl)-1-(2,2,2-trichloro-1,1-dimethyl-ethoxycarbonyl)-pyridinium; chloride [ No CAS ]

References: [1]Tetrahedron Asymmetry,2006,vol. 17,p. 1007 - 1016.
[2]Tetrahedron Asymmetry,2006,vol. 17,p. 1007 - 1016.

11
[ 60159-37-7 ]
2-((S)-1-Butoxy-ethyl)-4-dimethylamino-1-(2,2,2-trichloro-1,1-dimethyl-ethoxycarbonyl)-pyridinium; chloride [ No CAS ]

References: [1]Tetrahedron Asymmetry,2006,vol. 17,p. 1007 - 1016.
[2]Tetrahedron Asymmetry,2006,vol. 17,p. 1007 - 1016.

12
[ 60159-37-7 ]
(R)-(+)-4-(N,N-dimethylamino)-2-(1-hydroxyethyl)pyridine [ No CAS ]

References: [1]Tetrahedron Asymmetry,2005,vol. 16,p. 3427 - 3435.

13
[ 60159-37-7 ]
[ 872036-42-5 ]

References: [1]Tetrahedron Asymmetry,2005,vol. 16,p. 3427 - 3435.

14
[ 60159-37-7 ]
[ 27911-63-3 ]

References: [1]Tetrahedron Asymmetry,2005,vol. 16,p. 3427 - 3435.

15
[ 60159-37-7 ]
[ 494190-96-4 ]

References: [1]Tetrahedron Asymmetry,2005,vol. 16,p. 3427 - 3435.

16
[ 1121-76-2 ]
[ 60159-37-7 ]

References: [1]Tetrahedron Asymmetry,2005,vol. 16,p. 3427 - 3435.

17
[ 60159-37-7 ]
[ 7022-37-9 ]
CH₂Cl₂:MeOH [ No CAS ]
[ 379226-88-7 ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; acetic acid;	EXAMPLE 11 1-(4-Chloro-2-pyridyl)-1-ethanone-1-(1-methyl-1H-benzo[d]imidazol-2-yl)-hydrazone (1d-4) A mixture of 2-acetyl-4-chloropyridine (0.50 g, 3.20 mmol) and 1-methyl-2-hydrazinobenzimidazole (0.52 g, 3.20 mmol) in 5 ml of methanol is stirred for 4 days at room temperature after the addition of 6 drops of glacial acetic acid. The reaction is monitored by means of thin layer chromatography (Polygram Sil G/UV254 prefabricated foils; eluding agent: CH2Cl2:MeOH (12:1)). Subsequently, the reaction mixture is diluted with distilled water until a precipitate forms and stored for 24 hours in the refrigerator at approximately 5 C. The precipitate is filtered, washed several times with water, and dried. The product is recrystallized from a mixture of methanol and water. Yield: 0.60 g (62% of theory). C15H14ClN5 (327.39) 1H-NMR (δ, ppm)=2.40 (s, 3H), 3.49 (s, 3H), 6.99-7.22 (m, 4H), 7.37 (dd, 1H), 8.50 (d, 1H), 8.56 (d, 1H), 11.25 (br. s, 1H).

References: [1]Patent: US2003/166658,2003,A1 .

18
[ 19235-89-3 ]
[ 60159-37-7 ]

Yield	Reaction Conditions	Operation in experiment
3.60 g (60%)	With hydrogenchloride; MeMgI; In benzene;	2-Acetyl-4-chloropyridine: To a solution of 4-chloro-2-pyridinecarbonitrile (5.35 g, 38.6 mmol) in benzene (50 ml) and ether (50 ml) cooled to 0 C. was added dropwise over 20 min a 2M solution of MeMgI in ether (23 ml, 46.3 mmol). After 0.5 h, the mixture was allowed to warm to ambient temperature, and stirring continued for 2 h. The mixture was cooled to 0 C. and 2M aqueous HCl (100 ml) added. The mixture was made basic with saturated aqueous sodium bicarbonate (~80 ml) and the organic layer separated and dried (MgSO4). After removal of solvent, the residue was purified by flash chromatography eluding with ethyl acetate/hexane (1:5) to afford 3.60 g (60%) of 2-acetyl-4-chloropyridine. 1H-NMR (DMSO-d6) δ: 8.59 (1H, d, J=5.1 Hz), 8.04 (1H, d, J=1.8 Hz), 7.47 (1H, dd, J=1.8, 5.1 Hz), 2.72 (3H, s).
3.60 g (60%)	With hydrogenchloride; MeMgI; In benzene;	2-Acetyl-4-chloropyridine: To a solution of 4-chloro-2-pyridinecarbonitrile (5.35 g, 38.6 mmol) in benzene (50 ml) and ether (50 ml) cooled to 0 C was added dropwise over 20 min a 2M solution of MeMgI in ether (23 ml, 46.3 mmol). After 0.5 h, the mixture was allowed to warm to ambient temperature, and stirring continued for 2 hours. The mixture was cooled to 0 C and 2M aqueous HCl (100 ml) added. Themixture was made basic with saturated aqueous sodium bicarbonate (~80 ml) and the organic layer separated and dried (MgSO4). After removal of solvent, the residue was purified by flash chromatography eluding with ethyl acetate/hexane (1:5) to afford 3.60 g (60%) of 2-acetyl-4-chloropyridine. 1H-NMR (DMSO-d6) 8.59 (1 H, d, J=5.1 Hz), 8.04 (1 H, d, J=1.8 Hz), 7.47 (1 H, dd, J=1.8, 5.1 Hz), 2.72 (3 H, s).

References: [1]Dalton Transactions,2017,vol. 46,p. 10996 - 11007.
[2]Patent: US6608070,2003,B1 .
[3]Patent: EP1065206,2001,A1 .

19
[ 60159-37-7 ]
2-(Bromoacetyl)-4-chloropyridine hydrobromide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		2-Bromoacetyl-4-chloropyridine hydrobromide: 2-(Bromoacetyl)-4-chloropyridine hydrobromide was prepared from 2-acetyl-4-chloropyridine according to the method of H. McKennis, Jr., L. B. Tumbull, E. R. Bowman, and E. Tamaki (in J. Org. Chem., 1963, 28, 383-387). 1H-NMR (DMSO-d6) δ: 8.74 (1H, d, J=5.5 Hz), 8.05 (1H, d, J=1.8 Hz), 7.88 (1H, dd, J=2.2 and 5.5 Hz), 5.02 (2H, s).
		2-Bromoacetyl-4-chloropyridine hydrobromide: 2-(Bromoacetyl)-4-chloropyridine hydrobromide was prepared from 2-acetyl-4-chloropyridine according to the method of H. McKennis, Jr., L. B. Turnbull, E. R. Bowman, and E. Tamaki (in J. Org. Chem.,1963, 28 , 383-387). 1H-NMR (DMSO-d6) 8.74 (1 H, d, J=5.5 Hz), 8.05 (1 H, d, J=1.8 Hz), 7.88 (1 H, dd, J=2.2 and 5.5 Hz), 5.02 (2 H, s).
		2-(Bromoacetyl)4-chloropyridine hydrobromide: 2-(Bromoacetyl)-4-chloropyridine hydrobromide was prepared from 2-acetyl-4-chloropyridine according to the method of H. McKennis, Jr., L. B. Tunbull, E. R. Bowman, and E. Tamaki (in J. Org. Chem., 1963,28,383-387S). 1H-NMR (DMSO-d6)δ 8.74 (1H, d, J=5.5 Hz), 8.05 (1H, d, J=1.8 Hz), 7.88 (1H, dd, J=2.2, 5.5 Hz), 5.02 (2H, s)

References: [1]Patent: US6608070,2003,B1 .
[2]Patent: EP1065206,2001,A1 .
[3]Patent: US6277878,2001,B1 .

20
[ 60159-37-7 ]
[ 1370545-04-2 ]

References: [1]Patent: WO2012/41873,2012,A1 .

21
[ 60159-37-7 ]
[ 107-21-1 ]
[ 126866-46-4 ]

Yield	Reaction Conditions	Operation in experiment
93%	toluene-4-sulfonic acid; In toluene;Reflux;	Step A: 4-Chloro-2-(2-methyl-1 ,3-dioxolan-2-yl)pyridine; 1-(4-Chloro-2-pyridyl)ethanone (440 mg, 2.83 mmol) and ethyleneglycol (480 mg, 3 mmol) were mixed with toluene (10 ml), a catalytic amount of p-toluenesulfonic acid was added and the mixture was heated at reflux overnight. The mixture was evaporated to dryness to yield 523 mg of a solid (2.6 mmol, 93%). MS (APCI) m/z = 200.0 [M+H]+.

References: [1]Patent: WO2012/41873,2012,A1 .Location in patent: Page/Page column 91.

22
[ 60159-37-7 ]
2-Bromo-1-(4-chloropyridin-2-yl)ethanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	With hydrogen bromide; bromine; acetic acid; at 75℃; for 3.5h;	Preparation 8 2-Bromo- 1 -(4-chloro-2-pyridyl)ethanone l-(4-Chloro-2-pyridyl)ethanone (24.4 g, 156.83 mmol) is dissolved in glacial acetic acid (224 mL) with stirring. A solution of hydrogen bromide (32% in acetic acid) (34 mL) is added followed by slow addition of bromine (8.2 mL, 159.97 mmol). The resulting solution is heated at 75 C for 3.5 hours and then is immediately cooled in an ice-bath. Saturated aqueous sodium hydrogen carbonate (1 L) is slowly added to the cooled reaction mixture with stirring, followed by solid sodium hydrogen carbonate to adjust the pH of the solution to 7. Ethyl acetate (400 mL) is then added and the layers are separated. The aqueous layer is re-extracted with ethyl acetate (3x400 mL). The organic extracts are combined, dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to give a brown crystalline solid. The isolated solid is trituated with isohexane and is further dried under vacuum to give the title compound (21 g). The product remaining in the isohexane is recovered by silica gel column chromatography using a 0 to 40% dichloromethane in isohexane gradient to give an additional 5.5 g of title product which gives a combined yield (26.5 g, 72%). ES/MS (m/e) 234/236/238 (M+l).
71%	With hydrogen bromide; bromine; acetic acid; at 75℃; for 0.25h;	Step B Pyridine ketone II (7.78 g, 50 mmol) is dissolved in conc. HOAc (100 ml), and HBr (11 ml of a 32% HBr solution in conc. HOAc, 60 mmol) is added. During the addition, a cloudy precipitate forms. Bromine (2.6 ml, 50 mmol) is added dropwise. The precipitate dissolves during the Br2 addition. The reaction mixture is stirred at 75 C. for 15 min. After cooling to room temperature, a precipitate forms. The suspension is added to saturated aqueous NaHCO3 solution (300 ml), and the resultant mixture is extracted with EtOAc (3*150 ml). The combined organic phases are washed with saturated aqueous sodium chloride solution (50 ml) and dried using Na2SO4. The solvents are subsequently removed under reduced pressure in a rotary evaporator. An orange oil (13.4 g) is obtained as crude product. The crude product is purified by column chromatography (200 g of Si60, gradient CH2Cl2/PE 1:3 to CH2Cl2/PE 1:1), and the suitable fractions (characterised by TLC analysis) are combined. Removal of the solvents gives ketobromide III (8.3 g, 35.4 mol, 71% yield) as pale yellow oil, which crystallises on extended storage. Analytical data of ketobromide III: TLC: Rf=0.66 (Si60, CH2Cl2/PE 1:1); m.p.: 72 C.; LC-MS: broad peak-tR=2.213 min (UV=220 nm), tR=2.194 min. (TIC, with [M]+=234); 1H NMR (400 MHz, CDCl3) δ 8.59 (d, J=5.2, 1H), 8.09 (d, J=2.0, 1H), 7.52 (dd, J=5.2, 2.1, 1H), 4.81 (s, 2H).
51%	With bromine; In ethanol; hydrogen bromide; at 0 - 25℃; for 2h;liquid HBr;	To a mixture of <strong>[60159-37-7]1-(4-chloro-2-pyridyl)ethanone</strong> (400 mg, 2.57 mmol) in HBr/AcOH (5 mL) was added Br2 (0.2 mL, 3.86 mmol) at 0 C, then the mixture was stirred at 25 C for 2 hours. The mixture was quenched with water (20 mL), then themixture was extracted with EtOAc (30 mL x 2). The combined organic phase was washed with sat.Na2CO3 (15 mL x 3) and brine (15 mL), dried over Na2SO4, filtered and concentrated to give the crude product (500 mg, 1.30 mmol, 51% yield) as a solid. LCMS Rt 0.75 mm in 1.5 mm chromatography, 5-95AB, purity 61.04%, MS ESI calcd. for C7H6BrCINO [M+H+2] 235.9, found 235.8.

References: [1]Patent: WO2015/138208,2015,A1 .Location in patent: Page/Page column 11-12.
[2]Patent: US2012/220587,2012,A1 .Location in patent: Page/Page column 19.
[3]Patent: WO2019/35951,2019,A1 .Location in patent: Page/Page column 58; 59.

23
[ 60159-37-7 ]
[ 1278594-96-9 ]