[ CAS No. 83570-42-7 ] {[proInfo.proName]}

Name: 83570-42-7|1-(Quinoxalin-6-yl)ethanone|98%
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SKU: A162199
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Quality Control of [ 83570-42-7 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 83570-42-7 ]

SDS Specification

Alternatived Products of [ 83570-42-7 ]

Product Details of [ 83570-42-7 ]

CAS No. :	83570-42-7	MDL No. :	MFCD09880611
Formula :	C₁₀H₈N₂O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	DZJNWCSVQXNMFO-UHFFFAOYSA-N
M.W :	172.18	Pubchem ID :	22631249
Synonyms :

Calculated chemistry of [ 83570-42-7 ]

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	10
Fraction Csp3 :	0.1
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	49.73
TPSA :	42.85 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) :	-6.45 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.57
Log Po/w (XLOGP3) :	1.27
Log Po/w (WLOGP) :	1.83
Log Po/w (MLOGP) :	0.53
Log Po/w (SILICOS-IT) :	2.25
Consensus Log Po/w :	1.49

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-2.21
Solubility :	1.06 mg/ml ; 0.00615 mol/l
Class :	Soluble
Log S (Ali) :	-1.77
Solubility :	2.93 mg/ml ; 0.017 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-3.66
Solubility :	0.0378 mg/ml ; 0.000219 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.38

Safety of [ 83570-42-7 ]

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

Application In Synthesis of [ 83570-42-7 ]

* 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.

Upstream synthesis route of [ 83570-42-7 ]
Downstream synthetic route of [ 83570-42-7 ]

[ 83570-42-7 ] Synthesis Path-Upstream 1~4

1
[ 50998-17-9 ]
[ 97674-02-7 ]
[ 83570-42-7 ]

Reference： [1] Patent: US2005/256309, 2005, A1, . Location in patent: Page/Page column 35
[2] Patent: US2005/272736, 2005, A1, . Location in patent: Page/Page column 35
[3] Patent: WO2016/30443, 2016, A1, . Location in patent: Page/Page column 80
[4] Patent: WO2017/144633, 2017, A1, . Location in patent: Page/Page column 95
[5] Patent: WO2017/144639, 2017, A1, . Location in patent: Page/Page column 80

2
[ 875558-38-6 ]
[ 75-16-1 ]
[ 83570-42-7 ]

Yield	Reaction Conditions	Operation in experiment
75.7%	at 0 - 20℃; for 2 h; Inert atmosphere	To a solution of Compound 2 (1 g, 4.6 mmol) in dry THF (10 mL) at 0 °C under N2 was added MeMgBr (2 mL, 3.0 mol/L, 6 mmol) dropwise. The resulting solution was slowly warm to RT over 2 hours. The mixture was diluted with NH4C1 solution and extracted with EA. The organic extracts were concentrated to give a crude oil. The crude product was purified by silica gel chromatography to afford Compound 3 (600 mg, 75.7 percent).
74%	at 0 - 20℃; for 3 h;	A mixture of quinoxaline-6-carboxylic acid (2 g, 11.49 mmol) and thionyl chloride (30 mL) was stirred at reflux for 2 hours. The reaction mixture was concentrated to dryness using a rotary evaporator to afford quinoxaline-6- EPO <DP n="101"/>carboxylic acid chloride (crude quantitative). A solution of the above acid chloride (11.49 mmol) in DCM (50 mL) and pyridine (20 mL) was mixed with N,O-dimethyl hydroxylamine HCI salt (2.24 g, 23 mmol) and stirred at room temperature for 12 hours. The reaction was quenched by adding aqueous HCI (50 mL, 1 N), extracted with DCM (3x100 mL), concentrated using a rotary evaporator. The residue was further purified by column (Siψ2, Hexanes/EtOAc = 1 :3) to yield quinoxaline-6-carboxylic acid methoxy-methyl-amide (2 g, 80percent). To a solution of the above Weinreb amide (2.0 g, 9.2 mmol) in THF (30 mL) at O⁰C was added methyl magnesium bromide (3.9 mL, 11.6 mmol). The reaction mixture was stirred at O⁰C for 2 hours and then 1 hour at room temperature, quenched by adding aqueous HCI (20 mL, 1 N), extracted with DCM (3x100 mL), concentrated using a rotary evaporator. The residue was further-purified by column (SiO₂, Hexanes/EtOAc = 1 :3) to yield 6-acetylquinoxaline (1.17 g, 74percent). A solution of 2- chloronicotinic acid ethyl ester (5.0 g, 27 mmol) in MeOH (25 mL) was mixed with sodium methoxide (25.6 mL, 112.5 mmol) and stirred at reflux for 12 hours. The reaction was quenched by adding water (100 mL), extracted with DCM (3x100 mL), concentrated using a rotary evaporator to afford 2-methoxynicotinic acid methyl ester (3.2 g, 71percent). A solution of 6-acetylquinoxaline (0.62 g, 3.6 mmol), 2- methoxynicotinic acid methyl ester (0.64 g, 3.8 mmol), and sodium hydride (0.46 g, 11.4 mmol) in THF (100 mL) was stirred at room temperature for 16 hours. The reaction was quenched by adding water (100 mL) and AcOH (20 mL), extracted with dichloromethane (3x100 mL), and concentrated using a rotary evaporator. The residue was re-dissolved in DCM (5 mL) and MeOH (3 mL) and was diluted with Hexanes (50 mL). The solid was removed by filtration and the filtrate was concentrated to afford the diketo compound (0.7 g, 60percent). A solution of the above diketone (0.4 g, 1.3 mmol) in AcOH (50 mL) and sulfuric acid (cone, 15 drops) was stirred at reflux for 1 hour. Most of the solvent was removed using a rotary evaporator. The residue was re-dissolved in MeOH and neutralized with potassium carbonate to pH = 8. The solid residue was removed by filtration, washed with MeOH and DCM. The filtrate was extracted with CH₂CI₂ (3x100 mL) and concentrated using a rotary evaporator. The solid residue was purified by column (SiO₂, Hexanes/EtOAc/MeOH = 2:2:1) to afford 2-(quinoxalin-6-yl)-4H- EPO <DP n="102"/>pyrano[2,3-b]pyridin-4-one (90 mg, 24percent); MS (ES) m/z: 276 (M+1 ); MP 272.3- 274.8⁰C

Reference： [1] Patent: WO2016/77232, 2016, A2, . Location in patent: Page/Page column 25; 33; 35; 37
[2] Patent: WO2007/16525, 2007, A2, . Location in patent: Page/Page column 99-101

3
[ 6925-00-4 ]
[ 83570-42-7 ]

Reference： [1] Patent: WO2016/77232, 2016, A2,

4
[ 1432-42-4 ]
[ 83570-42-7 ]

Reference： [1] Journal of the Chemical Society, 1956, p. 2058,2060

[ 83570-42-7 ] Synthesis Path-Downstream 1~78

1
[ 1432-42-4 ]
[ 83570-42-7 ]

Reference： [1]Journal of the Chemical Society,1956,p. 2058,2060

2
1-{3-[2-(Phenyl-hydrazono)-eth-(E)-ylideneamino]-phenyl}-ethanone [ No CAS ]
[ 83570-42-7 ]
[ 62-53-3 ]
[ 98-86-2 ]
1-(quinoxalin-5-yl)ethanone [ No CAS ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1982,p. 1941 - 1946

3
1-{4-[2-(Phenyl-hydrazono)-eth-(E)-ylideneamino]-phenyl}-ethanone [ No CAS ]
[ 83570-42-7 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1982,p. 1941 - 1946

4
[ 50998-17-9 ]
[ 97674-02-7 ]
[ 83570-42-7 ]

Yield	Reaction Conditions	Operation in experiment
		A solution of 6-bromo-quinoxaline (261 mg, 1.25 mmol), 1-ethoxyvinyltri-n-butyltin (0.47 mL, 1.4 mmol), palladium(II) acetate (16 mg) and tri-t-butylphosphonium tetrafluoroborate (41 mg) in anhydrous DMF (4 mL) under a nitrogen atmosphere was heated at 120 C. for 1 hr. The reaction mixture was cooled to ambient temperature and partitioned between ethyl acetate (25 mL) and H2O (10 mL). The organic extraction was washed with brine, dried (MgSO4), filtered, and concentrated. The concentrate was chromatographed on silica gel eluting with ethyl acetate:hexanes (1:1) to provide 110 mg of the title compound. 1H NMR (300 MHz, CDCl3) delta 2.79 (s, 3H), 8.18 (d, J=9 Hz, 1H), 8.36 (dd, J=9 Hz, J=3 Hz, 1H), 8.70 (d, J=3 Hz, 1H), 8.95 (s, 2H); MS (DCl/NH3) m/z 173 (M+H)+.
	With tri tert-butylphosphoniumtetrafluoroborate;palladium diacetate; In DMF (N,N-dimethyl-formamide); at 120℃; for 1h;	Example 13A 1-Quinoxalin-6-yl-ethanone A solution of 6-bromo-quinoxaline (261 mg, 1.25 mmol), 1-ethoxyvinyltri-n-butyltin (0.47 mL, 1.4 mmol), palladium(II) acetate (16 mg) and tri-t-butylphosphonium tetrafluoroborate (41 mg) in anhydrous DMF (4 mL) under a nitrogen atmosphere was heated at 120 C. for 1 hr. The reaction mixture was cooled to ambient temperature and partitioned between ethyl acetate (25 mL) and H2O (10 mL). The organic extraction was washed with brine, dried (MgSO4), filtered, and concentrated. The concentrate was chromatographed on silica gel eluding with ethyl acetate:hexanes (1:1) to provide 110 mg of the title compound. 1H NMR (300 MHz, CDCl3) delta 2.79 (s, 3H), 8.18 (d, J=9 Hz, 1H), 8.36 (dd, J=9 Hz, J=3 Hz, 1H), 8.70 (d, J=3 Hz, 1H), 8.95 (s, 2H); MS (DCl/NH3) m/z 173 (M+H)+.
		6-Bromo quinoxaline (2.0 g, 9.5 mmol) in toluene (20 ml.) was degassed for 30 min. To this solution, 1-ethoxy vinyl tributyltin (3.8 g, 10.5 mmol) and bis(triphenylphosphine)palladium dichloride (0.67 g, 0.95 mmol) were added at rt and stirred for 16 hours at 90 C. The reaction mixture was cooled to rt and filtered through celite. After evaporation of the solvent, 6 N HCl solution in water (20 ml.) was added and the mixture was stirred for 1 hour at rt. It was concentrated and neutralized with sat. NaHCO3. The desired product was extracted with DCM (100 mL,), dried over Na2SO4 and concentrated. The crude product was purified by flash column chromatography to afford the title compound (brown solid). 1H NMR (400 MHz, DMSO-d6): delta 9.06-9.04 (m, 2H), 8.70 (d, J=2.4 Hz, 1H), 8.28 (t, J = 2.8 Hz, 1H), 8.16 (d, J = 11.6 Hz, 1H), 2.97 (s, 3H). LCMS: (Method A) 173 (M+H), Rt. 2.25 min, 99.06% (Max).

		6-Bromo quinoxaline (2.0 g, 9.5 mmcl) in toluene (20 mL) was degassed for 30 mm. To thissolution, 1-ethoxy vinyl tributyltin (3.8 g, 10.5 mmol) and bis(triphenylphosphine)palladium dichloride (0.67 g, 0.95 mmol) were added at rt and stirred for 16 hours at 90 C. The reaction mixture was cooled to rt and filtered through celite. After evaporation of the solvent, 6 N HCI solution in water (20 mL) was added and the mixture was stirred for I hour at rt. It was concentrated and neutralized with sat. NaHCO3. The desired product wasextracted with DCM (100 mL), dried over Na2SO4 and concentrated. The crude productwas purified by column chromatography to afford the title compound (brown solid). 1H NMR(400 MHz, DMSO-d6): 6 9.06-9.04 (m, 2H), 8.70 (d, J=2.4 Hz, I H), 8.28 (t, J = 2.8 Hz, I H),8.16 (d, J = 11.6 Hz, IH), 2.97 (5, 3H). LCMS: (Method A) 173 (M+H), Rt. 2.25 mm,99.06% (Max).
	With bis-triphenylphosphine-palladium(II) chloride; In toluene; at 90℃; for 16h;Inert atmosphere;	6-Bromo quinoxaline (2.0 g, 9.5 mmol) in toluene (20 mL) was degassed for 30 min. To this solution, 1-ethoxy vinyl tributyltin (3.8 g, 10.5 mmol) and bis(triphenylphosphine)palladium dichloride (0.67 g, 0.95 mmol) were added at rt and stirred for 16 hours at 90 C. The reaction mixture was cooled to rt and filtered through celite. After evaporation of the solvent, 6 N HCI solution in water (20 mL) was added and the mixture was stirred for 1 hour at rt. It was concentrated and neutralized with sat. NaHCO3. The desired product was extracted with DCM (100 mL), dried over Na2SO4 and concentrated. The crude product was purified by column chromatography to afford the title compound (brown solid). 1H NMR (400 MHz, DMSO-de): delta 9.06-9.04 (m, 2H), 8.70 (d, J=2.4 Hz, 1 H), 8.28 (t, J = 2.8 Hz, 1 H), 8.16 (d, J = 11.6 Hz, 1 H), 2.97 (s, 3H). LCMS: (Method A) 173 (M+H), Rt. 2.25 min, 99.06% (Max).

Reference： [1]Patent: US2005/256309,2005,A1 .Location in patent: Page/Page column 35
[2]Patent: US2005/272736,2005,A1 .Location in patent: Page/Page column 35
[3]Patent: WO2016/30443,2016,A1 .Location in patent: Page/Page column 80
[4]Patent: WO2017/144633,2017,A1 .Location in patent: Page/Page column 95
[5]Patent: WO2017/144639,2017,A1 .Location in patent: Page/Page column 80

5
[ 875558-38-6 ]
[ 75-16-1 ]
[ 83570-42-7 ]

Yield	Reaction Conditions	Operation in experiment
75.7%	In tetrahydrofuran; at 0 - 20℃; for 2h;Inert atmosphere;	To a solution of Compound 2 (1 g, 4.6 mmol) in dry THF (10 mL) at 0 C under N2 was added MeMgBr (2 mL, 3.0 mol/L, 6 mmol) dropwise. The resulting solution was slowly warm to RT over 2 hours. The mixture was diluted with NH4C1 solution and extracted with EA. The organic extracts were concentrated to give a crude oil. The crude product was purified by silica gel chromatography to afford Compound 3 (600 mg, 75.7 %).
74%	In tetrahydrofuran; at 0 - 20℃; for 3h;	A mixture of quinoxaline-6-carboxylic acid (2 g, 11.49 mmol) and thionyl chloride (30 mL) was stirred at reflux for 2 hours. The reaction mixture was concentrated to dryness using a rotary evaporator to afford quinoxaline-6- EPO <DP n="101"/>carboxylic acid chloride (crude quantitative). A solution of the above acid chloride (11.49 mmol) in DCM (50 mL) and pyridine (20 mL) was mixed with N,O-dimethyl hydroxylamine HCI salt (2.24 g, 23 mmol) and stirred at room temperature for 12 hours. The reaction was quenched by adding aqueous HCI (50 mL, 1 N), extracted with DCM (3x100 mL), concentrated using a rotary evaporator. The residue was further purified by column (Sitheta2, Hexanes/EtOAc = 1 :3) to yield quinoxaline-6-carboxylic acid methoxy-methyl-amide (2 g, 80%). To a solution of the above Weinreb amide (2.0 g, 9.2 mmol) in THF (30 mL) at O0C was added methyl magnesium bromide (3.9 mL, 11.6 mmol). The reaction mixture was stirred at O0C for 2 hours and then 1 hour at room temperature, quenched by adding aqueous HCI (20 mL, 1 N), extracted with DCM (3x100 mL), concentrated using a rotary evaporator. The residue was further-purified by column (SiO2, Hexanes/EtOAc = 1 :3) to yield 6-acetylquinoxaline (1.17 g, 74%). A solution of 2- chloronicotinic acid ethyl ester (5.0 g, 27 mmol) in MeOH (25 mL) was mixed with sodium methoxide (25.6 mL, 112.5 mmol) and stirred at reflux for 12 hours. The reaction was quenched by adding water (100 mL), extracted with DCM (3x100 mL), concentrated using a rotary evaporator to afford 2-methoxynicotinic acid methyl ester (3.2 g, 71%). A solution of 6-acetylquinoxaline (0.62 g, 3.6 mmol), 2- methoxynicotinic acid methyl ester (0.64 g, 3.8 mmol), and sodium hydride (0.46 g, 11.4 mmol) in THF (100 mL) was stirred at room temperature for 16 hours. The reaction was quenched by adding water (100 mL) and AcOH (20 mL), extracted with dichloromethane (3x100 mL), and concentrated using a rotary evaporator. The residue was re-dissolved in DCM (5 mL) and MeOH (3 mL) and was diluted with Hexanes (50 mL). The solid was removed by filtration and the filtrate was concentrated to afford the diketo compound (0.7 g, 60%). A solution of the above diketone (0.4 g, 1.3 mmol) in AcOH (50 mL) and sulfuric acid (cone, 15 drops) was stirred at reflux for 1 hour. Most of the solvent was removed using a rotary evaporator. The residue was re-dissolved in MeOH and neutralized with potassium carbonate to pH = 8. The solid residue was removed by filtration, washed with MeOH and DCM. The filtrate was extracted with CH2CI2 (3x100 mL) and concentrated using a rotary evaporator. The solid residue was purified by column (SiO2, Hexanes/EtOAc/MeOH = 2:2:1) to afford 2-(quinoxalin-6-yl)-4H- EPO <DP n="102"/>pyrano[2,3-b]pyridin-4-one (90 mg, 24%); MS (ES) m/z: 276 (M+1 ); MP 272.3- 274.80C

Reference： [1]Patent: WO2016/77232,2016,A2 .Location in patent: Page/Page column 25; 33; 35; 37
[2]Patent: WO2007/16525,2007,A2 .Location in patent: Page/Page column 99-101

6
[ 67367-26-4 ]
[ 83570-42-7 ]
[ 924300-45-8 ]

Yield	Reaction Conditions	Operation in experiment
60%	With sodium hydride; In tetrahydrofuran; at 20℃; for 16h;	A mixture of quinoxaline-6-carboxylic acid (2 g, 11.49 mmol) and thionyl chloride (30 mL) was stirred at reflux for 2 hours. The reaction mixture was concentrated to dryness using a rotary evaporator to afford quinoxaline-6- EPO <DP n="101"/>carboxylic acid chloride (crude quantitative). A solution of the above acid chloride (11.49 mmol) in DCM (50 mL) and pyridine (20 mL) was mixed with N,O-dimethyl hydroxylamine HCI salt (2.24 g, 23 mmol) and stirred at room temperature for 12 hours. The reaction was quenched by adding aqueous HCI (50 mL, 1 N), extracted with DCM (3x100 mL), concentrated using a rotary evaporator. The residue was further purified by column (Sitheta2, Hexanes/EtOAc = 1 :3) to yield quinoxaline-6-carboxylic acid methoxy-methyl-amide (2 g, 80%). To a solution of the above Weinreb amide (2.0 g, 9.2 mmol) in THF (30 mL) at O0C was added methyl magnesium bromide (3.9 mL, 11.6 mmol). The reaction mixture was stirred at O0C for 2 hours and then 1 hour at room temperature, quenched by adding aqueous HCI (20 mL, 1 N), extracted with DCM (3x100 mL), concentrated using a rotary evaporator. The residue was further-purified by column (SiO2, Hexanes/EtOAc = 1 :3) to yield <strong>[83570-42-7]6-acetylquinoxaline</strong> (1.17 g, 74%). A solution of 2- chloronicotinic acid ethyl ester (5.0 g, 27 mmol) in MeOH (25 mL) was mixed with sodium methoxide (25.6 mL, 112.5 mmol) and stirred at reflux for 12 hours. The reaction was quenched by adding water (100 mL), extracted with DCM (3x100 mL), concentrated using a rotary evaporator to afford 2-methoxynicotinic acid methyl ester (3.2 g, 71%). A solution of <strong>[83570-42-7]6-acetylquinoxaline</strong> (0.62 g, 3.6 mmol), 2- methoxynicotinic acid methyl ester (0.64 g, 3.8 mmol), and sodium hydride (0.46 g, 11.4 mmol) in THF (100 mL) was stirred at room temperature for 16 hours. The reaction was quenched by adding water (100 mL) and AcOH (20 mL), extracted with dichloromethane (3x100 mL), and concentrated using a rotary evaporator. The residue was re-dissolved in DCM (5 mL) and MeOH (3 mL) and was diluted with Hexanes (50 mL). The solid was removed by filtration and the filtrate was concentrated to afford the diketo compound (0.7 g, 60%). A solution of the above diketone (0.4 g, 1.3 mmol) in AcOH (50 mL) and sulfuric acid (cone, 15 drops) was stirred at reflux for 1 hour. Most of the solvent was removed using a rotary evaporator. The residue was re-dissolved in MeOH and neutralized with potassium carbonate to pH = 8. The solid residue was removed by filtration, washed with MeOH and DCM. The filtrate was extracted with CH2CI2 (3x100 mL) and concentrated using a rotary evaporator. The solid residue was purified by column (SiO2, Hexanes/EtOAc/MeOH = 2:2:1) to afford 2-(quinoxalin-6-yl)-4H- EPO <DP n="102"/>pyrano[2,3-b]pyridin-4-one (90 mg, 24%); MS (ES) m/z: 276 (M+1 ); MP 272.3- 274.80C

Reference： [1]Patent: WO2007/16525,2007,A2 .Location in patent: Page/Page column 99-101

7
[ 689291-70-1 ]
[ 83570-42-7 ]
[ 869646-02-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 3295 - 3300

8
[ 83570-42-7 ]
1-(quinoxalin-6-yl)ethan-1-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium tetrahydroborate; In methanol; at 0℃; for 1h;	To a stirred solution of <strong>[83570-42-7]1-(quinoxalin-6-yl)ethan-1-one</strong> (0.8 g,4.65mmol) in dry MeOH (20 mL), sodium borohydride (0.36 g, 9.3 mmol) was added portion wise at 0 C and the resulting mixture was stirred for 1 h. It was then concentrated, diluted with DCM (80 mL), washed with water (20 mL), dried over Na2SO4 and concentrated. The crude product was taken for next step without further purification. Yield: 75% (600 mg, dark brown liquid). 1H NMR (400 MHz, DMSO-d6): delta 8.91-8.89 (m, 2H), 8.03 (t, J = 11.6 Hz, 2H), 7.87-7.86 (m, 1H), 5.49 (d, J = 5.9 Hz, 1H), 4.97 (t, J = 6.2 Hz, 1H), 1.42 (d, J = 8.6 Hz, 3H). LCMS: (Method A) 175.0 (M+H), Rt. 1 .89 min, 95.0% (Max).
	With methanol; sodium tetrahydroborate; at 0℃; for 1h;	To a stirred solution of <strong>[83570-42-7]1-(quinoxalin-6-yl)ethan-1-one</strong> (0.8 g,4.6Smmol) in dry MeOH (20 mL), sodium borohydride (0.36 g, 9.3 mmol ) was added portion wise at 0 C and the resulting mixture was stirred for lh. It was then concentrated, diluted with DCM (80 mL), washed with water (20 mL), dried over Na2SO4 and concentrated. The crude product wastaken for next step without further purification. Yield: 75% (600 mg, dark brown liquid). 1H NMR (400 MHz, DMSO-d6): 6 8.91-8.89 (m, 2H), 8.03 (t, J = 11.6 Hz, 2H), 7.87-7.86 (m, IH), 5.49 (d, J = 5.9 Hz, IH), 4.97 (t, J = 6.2 Hz, IH), 1.42 (d, J = 8.6 Hz, 3H). LCMS:(Method A) 175.0 (M+H), Rt. 1.89 mm, 95.0% (Max).
	With methanol; sodium tetrahydroborate; at 0℃; for 1h;	To a stirred solution of 1-(quinoxalin-6-yl)ethan-1 -one (0.8 g,4.65mmol) in dry MeOH (20 mL), sodium borohydride (0.36 g, 9.3 mmol ) was added portion wise at 0 C and the resulting mixture was stirred for 1 h. It was then concentrated, diluted with DCM (80 mL), washed with water (20 mL), dried over Na2SO4 and concentrated. The crude product was taken for next step without further purification. Yield: 75% (600 mg, dark brown liquid). 1H NMR (400 MHz, DMSO-d6): delta 8.91 -8.89 (m, 2H), 8.03 (t, J = 11.6 Hz, 2H), 7.87-7.86 (m, 1 H), 5.49 (d, J = 5.9 Hz, 1 H), 4.97 (t, J = 6.2 Hz, 1 H), 1.42 (d, J = 8.6 Hz, 3H). LCMS: (Method A) 175.0 (M+H), Rt. 1.89 min, 95.0% (Max).

600 mg

With sodium tetrahydroborate; In methanol; at 0℃; for 1h;

To a stirred solution of <strong>[83570-42-7]1-(quinoxalin-6-yl)ethan-1-one</strong> (0.8 g,4.65 mmol) in dry methanol (20 mL) at 0 C, NaBH4 (0.36 g, 9.30 mmol) was added portion wise and the resulting mixture was stirred for 1 h. After completion of the reaction (monitored by TLC), the mixture was quenched with ice cold water and the aqueous layer was extracted with DCM (2 x 40 mL). The combined organic layer was washed with water (20 mL), dried over anhydrous Na2S04 and concentrated under vacuum. The resulting crude material was forwarded to the next step without any further purification. Yield: 75% (600 mg, dark brown liquid). 1H NMR (400 MHz, DMSO-cfe): delta 8.91-8.89 (m, 2H), 8.03 (t, J = 1 1.6 Hz, 2H), 7.87-7.86 (m, 1 H), 5.49 (d, J = 5.9 Hz, 1 H), 4.98-4.97 (m, 1 H), 1.42 (d, J = 8.6 Hz, 3H). LCMS: (Method A) 175.0 (M+H), Rt. 1.89 min, 95.0% (Max).

Reference： [1]Patent: WO2016/30443,2016,A1 .Location in patent: Page/Page column 80
[2]Patent: WO2017/144633,2017,A1 .Location in patent: Page/Page column 95
[3]Patent: WO2017/144639,2017,A1 .Location in patent: Page/Page column 80
[4]Patent: WO2019/37860,2019,A1 .Location in patent: Page/Page column 68-69

9
[ 83570-42-7 ]
6-(1-chloroethyl)quinoxaline [ No CAS ]

Reference： [1]Patent: WO2016/30443,2016,A1
[2]Patent: WO2017/144633,2017,A1
[3]Patent: WO2017/144639,2017,A1
[4]Patent: WO2019/37860,2019,A1

10
[ 83570-42-7 ]
N-(5-(4-(1-(quinoxalin-6-yl)ethyl)piperazin-1-yl)-1,3,4-thiadiazol-2-yl)acetamide [ No CAS ]

Reference： [1]Patent: WO2016/30443,2016,A1

11
[ 83570-42-7 ]
6-(1-(4-(pyrimidin-2-yl)piperazin-1-yl)ethyl)quinoxaline [ No CAS ]

Reference： [1]Patent: WO2016/30443,2016,A1

12
[ 83570-42-7 ]
(R)-N-(5-(4-(1-(quinoxalin-6-yl)ethyl)piperazin-1-yl)-1,3,4-thiadiazol-2-yl)acetamide [ No CAS ]
(S)-N-(5-(4-(1-(quinoxalin-6-yl)ethyl)piperazin-1-yl)-1,3,4-thiadiazol-2-yl)acetamide [ No CAS ]

Reference： [1]Patent: WO2016/30443,2016,A1

13
[ 83570-42-7 ]
ethyl 2-(4-(1-(quinoxalin-6-yl)ethyl)piperazin-1-yl)thiazole-5-carboxylate [ No CAS ]

Reference： [1]Patent: WO2016/30443,2016,A1

14
[ 83570-42-7 ]
2-(4-(1-(quinoxalin-6-yl)ethyl)piperazin-1-yl)thiazole-5-carboxylic acid [ No CAS ]

Reference： [1]Patent: WO2016/30443,2016,A1

15
[ 83570-42-7 ]
N-methyl-2-(4-(1-(quinoxalin-6-yl)ethyl)piperazin-1-yl)thiazole-5-carboxamide [ No CAS ]

Reference： [1]Patent: WO2016/30443,2016,A1

16
[ 83570-42-7 ]
N-(2-(4-(1-(quinoxalin-6-yl)ethyl)piperazin-1-yl)pyrimidin-5-yl)acetamide [ No CAS ]

Reference： [1]Patent: WO2016/30443,2016,A1

17
[ 83570-42-7 ]
6-(1-(4-(4-(trifluoromethyl)pyrimidin-2-yl)piperazin-1-yl)ethyl)quinoxaline [ No CAS ]

Reference： [1]Patent: WO2016/30443,2016,A1

18
[ 83570-42-7 ]
6-(1-(4-(5-methylpyrimidin-2-yl)piperazin-1-yl)ethyl)quinoxaline [ No CAS ]

Reference： [1]Patent: WO2016/30443,2016,A1

19
[ 83570-42-7 ]
(R)-6-(1-(4-(5-(trifluoromethyl)pyrimidin-2-yl)piperazin-1-yl)ethyl)quinoxaline [ No CAS ]
(S)-6-(1-(4-(5-(trifluoromethyl)pyrimidin-2-yl)piperazin-1-yl)ethyl)quinoxaline [ No CAS ]

Reference： [1]Patent: WO2016/30443,2016,A1

20
[ 83570-42-7 ]
2-(4-(1-(quinoxalin-6-yl)ethyl)piperazin-1-yl)benzo[d]thiazole [ No CAS ]

Reference： [1]Patent: WO2016/30443,2016,A1

21
[ 83570-42-7 ]
2-(4-(1-(quinoxalin-6-yl)ethyl)piperazin-1-yl)thiazolo[4,5-c]pyridine [ No CAS ]

Reference： [1]Patent: WO2016/30443,2016,A1

22
[ 83570-42-7 ]
6-(1-(4-(5-(trifluoromethyl)pyridin-2-yl)piperazin-1-yl)ethyl)quinoxaline [ No CAS ]

Reference： [1]Patent: WO2016/30443,2016,A1

23
[ 83570-42-7 ]
6-(1-(4-(5-fluoropyrimidin-2-yl)piperazin-1-yl)ethyl)quinoxaline [ No CAS ]

Reference： [1]Patent: WO2016/30443,2016,A1

24
[ 83570-42-7 ]
2-(4-(1-(quinoxalin-6-yl)ethyl)piperazin-1-yl)-6,7-dihydrothiazolo[5,4-c]pyridin-4(5H)-one [ No CAS ]

Reference： [1]Patent: WO2016/30443,2016,A1

25
[ 83570-42-7 ]
C₁₉H₂₂N₆O [ No CAS ]

Reference： [1]Patent: WO2016/30443,2016,A1

26
[ 83570-42-7 ]
tert-butyl 4-(1-(quinoxalin-6-yl) ethyl) piperazine-1-carboxylate [ No CAS ]

Reference： [1]Patent: WO2016/30443,2016,A1
[2]Patent: WO2017/144639,2017,A1
[3]Patent: WO2019/37860,2019,A1

27
[ 83570-42-7 ]
6-(1-(piperazin-1-yl)ethyl)quinoxaline hydrochloride [ No CAS ]

Reference： [1]Patent: WO2016/30443,2016,A1

28
[ 83570-42-7 ]
C₂₂H₂₀N₄OS [ No CAS ]

Reference： [1]Patent: WO2016/77232,2016,A2

29
[ 83570-42-7 ]
C₂₂H₂₀N₄S [ No CAS ]
C₂₂H₁₈N₄S [ No CAS ]

Reference： [1]Patent: WO2016/77232,2016,A2

30
[ 83570-42-7 ]
C₁₃H₁₀ClN₃S [ No CAS ]

Reference： [1]Patent: WO2016/77232,2016,A2

31
[ 83570-42-7 ]
C₂₃H₂₂N₄S [ No CAS ]

Reference： [1]Patent: WO2016/77232,2016,A2

32
[ 83570-42-7 ]
C₂₅H₂₆N₄S [ No CAS ]

Reference： [1]Patent: WO2016/77232,2016,A2

33
[ 83570-42-7 ]
C₁₃H₈ClN₃S [ No CAS ]

Reference： [1]Patent: WO2016/77232,2016,A2

34
[ 83570-42-7 ]
C₂₀H₁₆N₄S [ No CAS ]

Reference： [1]Patent: WO2016/77232,2016,A2

35
[ 3034-52-4 ]
[ 83570-42-7 ]
C₁₃H₁₀ClN₃OS [ No CAS ]
C₁₆H₁₁ClN₄OS₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76.2%; 2%		To a solution of 2-chlorothiazole (1 g, 8.4 mmol) in dry THF (10 mL) at -78 C under N2 was added n-BuLi (3.5 mL, 9.2 mmol) dropwise and the mixture stirred for 1 h. A solution of Compound 3 (1.3 g, 7.6 mmol) in dry THF (5 mL) was added dropwise to the reaction mixture at -78 C. The resulting solution was slowly warm to RT. The reaction was diluted with NH4C1 solution and extracted with EA. The organic extracts were concentrated to give a crude oil. The crude product was purified by silica gel chromatography to afford Example 1 (55 mg, 2 %) and Compound 4 (1.6 g, 76.2 %).Example 1: 1HNMR (CDC13, 300 MHz) oe: 2.0-2.2 (s, 3 H), 4.1-4.2 (s, 1 H), 7.3-7.4 (s,1 H), 7.8-7.9 (d, 1 H), 8.0-8.1 (d, 1 H), 8.2-8.3 (s, 1 H), 8.8 (m, 1 H), 9.0 (s, 1 H), 9.3-9.4(m, 1 H).LC-MS: mlz=375.1 (M+1) .

Reference： [1]Patent: WO2016/77232,2016,A2 .Location in patent: Page/Page column 25; 26; 33; 34; 35; 36; 37; 38

36
[ 6925-00-4 ]
[ 83570-42-7 ]

Reference： [1]Patent: WO2016/77232,2016,A2

37
[ 83570-42-7 ]
2-methyl-5-(1-(1-(quinoxalin-6-yl)ethyl)piperidin-4-yl)-1,3,4-oxadiazole [ No CAS ]

Reference： [1]Patent: WO2017/144633,2017,A1
[2]Patent: WO2017/144639,2017,A1

38
[ 83570-42-7 ]
N-(1-(1-(1-(quinoxalin-6-yl)ethyl)piperidin-4-yl)-1H-pyrazol-4-yl)acetamide [ No CAS ]

Reference： [1]Patent: WO2017/144633,2017,A1
[2]Patent: WO2017/144639,2017,A1

39
[ 83570-42-7 ]
6-(1-(4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)piperazin-1-yl)ethyl)quinoxaline [ No CAS ]

Reference： [1]Patent: WO2017/144633,2017,A1

40
[ 83570-42-7 ]
methyl-6-(4-(1-(quinoxalin-6-yl)ethyl)piperazin-1-yl)nicotinate [ No CAS ]

Reference： [1]Patent: WO2017/144633,2017,A1
[2]Patent: WO2017/144639,2017,A1

41
[ 83570-42-7 ]
6-(4-(1-(quinoxalin-6-yl)ethyl)piperazin-1-yl)nicotinic acid [ No CAS ]

Reference： [1]Patent: WO2017/144633,2017,A1
[2]Patent: WO2017/144639,2017,A1

42
[ 83570-42-7 ]
6-(1-(4-(5-bromopyrimidin-2-yl)piperazin-1-yl)ethyl)quinoxaline [ No CAS ]

Reference： [1]Patent: WO2017/144633,2017,A1
[2]Patent: WO2017/144639,2017,A1

43
[ 83570-42-7 ]
2-(2-(4-(1-(quinoxalin-6-yl)ethyl)piperazin-1-yl)pyrimidin-5-yl)propan-2-ol [ No CAS ]

Reference： [1]Patent: WO2017/144633,2017,A1
[2]Patent: WO2017/144639,2017,A1

44
[ 83570-42-7 ]
methyl 2-(4-(1-(quinoxalin-6-yl)ethyl)piperazin-1-yl)pyrimidine-5-carboxylate [ No CAS ]

Reference： [1]Patent: WO2017/144633,2017,A1
[2]Patent: WO2017/144639,2017,A1

45
[ 83570-42-7 ]
2-(4-(1-(quinoxalin-6-yl)ethyl)piperazin-1-yl)pyrimidine-5-carboxylic acid [ No CAS ]

Reference： [1]Patent: WO2017/144633,2017,A1
[2]Patent: WO2017/144639,2017,A1

46
[ 83570-42-7 ]
6-(1-(piperazin-1-yl) ethyl)quinoxaline hydrochloride [ No CAS ]

Reference： [1]Patent: WO2017/144639,2017,A1
[2]Patent: WO2019/37860,2019,A1

47
[ 83570-42-7 ]
2-(4-(1-(quinoxalin-6-yl)ethyl)piperazin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine [ No CAS ]