[ CAS No. 203395-59-9 ] {[proInfo.proName]}

Name: 203395-59-9|7-(4-Bromobutoxy)quinolin-2(1H)-one|95%
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Quality Control of [ 203395-59-9 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 203395-59-9 ]

CAS No. :	203395-59-9	MDL No. :	MFCD09753615
Formula :	C₁₃H₁₄BrNO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	MBOHAVAGDOGRBS-UHFFFAOYSA-N
M.W :	296.16	Pubchem ID :	10756315
Synonyms :

Calculated chemistry of [ 203395-59-9 ]

Physicochemical Properties

Num. heavy atoms :	17
Num. arom. heavy atoms :	10
Fraction Csp3 :	0.31
Num. rotatable bonds :	5
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	73.35
TPSA :	42.09 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.13 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.76
Log Po/w (XLOGP3) :	2.78
Log Po/w (WLOGP) :	3.08
Log Po/w (MLOGP) :	2.58
Log Po/w (SILICOS-IT) :	4.15
Consensus Log Po/w :	3.07

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.53
Solubility :	0.0868 mg/ml ; 0.000293 mol/l
Class :	Soluble
Log S (Ali) :	-3.32
Solubility :	0.142 mg/ml ; 0.000479 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-5.81
Solubility :	0.000459 mg/ml ; 0.00000155 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	0.0
Synthetic accessibility :	2.08

Safety of [ 203395-59-9 ]

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 [ 203395-59-9 ]

* 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 [ 203395-59-9 ]
Downstream synthetic route of [ 203395-59-9 ]

[ 203395-59-9 ] Synthesis Path-Upstream 1~7

1
[ 129722-34-5 ]
[ 203395-59-9 ]

Yield	Reaction Conditions	Operation in experiment
98.99%	With 2,3-dicyano-5,6-dichloro-p-benzoquinone In tetrahydrofuran at 20℃; for 12 h; Inert atmosphere	To a 500 mL two-neck round-bottom flask fitted with a magneticstir bar and argon inlet was charged 7-[4-bromobutoxy]-3,4-dihydro-2(1H)-quinolinone 5b (10 g, 0.033 mol) in THF(200 mL). To the aforementioned mixture 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (30.4 g, 0.13 mol) was added and the contents were stirred at rt until the completion of the reaction.Upon the consumption of starting material (as indicatedby TLC), THF was evaporated under reduced pressure. Theresidual product obtained was washed with water (200 mL)and extracted with ethyl acetate (3 × 100 mL). The organiclayer was washed with brine, dried over anhydrous Na2SO4,and concentrated under reduced pressure to furnish the crudeproduct. The crude product was purified by column chromatographyusing Ethyl acetate and n-Hexane as solventsystem to afford the title compound 8b.Yield: 98.99percent (9.8 g);1H NMR (400 MHz, DMSO-d6) δ 11.57 (s, 1H), 7.77 (d,J = 9.4 Hz, 1H), 7.53 (d, J = 9.4 Hz, 1H), 6.83–6.69 (m,2H), 6.27 (d, J = 9.6 Hz, 1H), 4.02 (t, J = 6.1 Hz, 2H), 3.59(t, J = 6.6 Hz, 2H), 2.03–1.89 (m, 2H), 1.89–1.74 (m, 2H);13C NMR (100 MHz, DMSO-d6): δ 162.67, 160.72, 141.05,140.44, 129.69, 118.97, 113.77, 111.19, 99.05, 67.28, 35.26,29.46, 27.74; ESI (MS): 296 [M+H]+; HPLC purity: 99.26percent[RT: 11.545 min; UV detection at 210 nm; Column: X BridgeC-18, 150 × 4.6 mm, 5 μm particle size; Mobile phase: A)0.1percent TFA in water, B) Acetonitrile; T/percentB: 0/10, 3/10, 15/95,23/95, 25/10, 30/10; Flowrate: 1.0 mL/min;Diluent:Acetonitrile:Water (80:20)]. 1H NMR spectral data of 8b was foundto be consistent with the values reported in Ref. 16.

Reference： [1] Journal of Chemical Sciences, 2018, vol. 130, # 6,
[2] Synthetic Communications, 2007, vol. 37, # 24, p. 4337 - 4341

2
[ 110-52-1 ]
[ 70500-72-0 ]
[ 203395-59-9 ]

Yield	Reaction Conditions	Operation in experiment
41%	With potassium carbonate In ethanolReflux	Intermediate 14:[0130] AICI₃ (11.5 g, 86.3 mmol) was added portion-wise to a suspension of intermediate 13 (4.2 g, 16.6 mmol) in chlorobenzene (90 mL) at 0°C. The reaction mixture was gradually warmed to 120^°C and stirred for 3 h. The mixture was poured into ice water and the resulting precipitate was collected by filtration, washed with water, and purified by flash chromatography on silica gel column (elution with DCM/MeOH = 60:1) to give 7-hydroxyquinolin-2(lH)-one (intermediate 14) (1.41 g, 53percent) as a white solid. Intermediate 15:

Reference： [1] Organic Process Research and Development, 2018, vol. 22, # 11, p. 1471 - 1480
[2] Patent: WO2012/3418, 2012, A2, . Location in patent: Page/Page column 51
[3] Journal of Medicinal Chemistry, 1998, vol. 41, # 5, p. 658 - 667
[4] Patent: WO2008/24481, 2008, A2, . Location in patent: Page/Page column 42
[5] Journal of Medicinal Chemistry, 2012, vol. 55, # 16, p. 7141 - 7153

3
[ 37783-33-8 ]
[ 203395-59-9 ]

Yield	Reaction Conditions	Operation in experiment
29.6 g	With 2,3-dicyano-5,6-dichloro-p-benzoquinone In 1,4-dioxane at 95℃; for 2 h;	Compound 2c (30g, 100.67mmol), DDQ (25.1g, 110 . 57mmol) into 1L reaction bottle, by adding 1,4-dioxane 300 ml, stirring under 95 °C 2 hours, TLC monitoring reaction is ended, concentrated under reduced pressure, by adding ice water, then adding sodium thiosulfate aqueous solution, stirring, add 3L dichloromethane extraction, separating the organic layer, an organic layer saturated salt water for washing, drying of anhydrous sodium sulfate, filtered, concentrated to obtain 29.6g strawcoloured solid 1c, almost quantitative yield, directly without further purification in the next step.

Reference： [1] Patent: CN105859703, 2016, A, . Location in patent: Paragraph 0214; 0215; 0216

4
[ 536-90-3 ]
[ 203395-59-9 ]

Reference： [1] Patent: WO2012/3418, 2012, A2,

5
[ 15116-41-3 ]
[ 203395-59-9 ]

Reference： [1] Patent: WO2012/3418, 2012, A2,

6
[ 41202-77-1 ]
[ 203395-59-9 ]
[ 129722-25-4 ]

Reference： [1] Journal of Medicinal Chemistry, 1998, vol. 41, # 5, p. 658 - 667

7
[ 203395-59-9 ]
[ 129722-25-4 ]

Reference： [1] Journal of Medicinal Chemistry, 2012, vol. 55, # 16, p. 7141 - 7153

[ 203395-59-9 ] Synthesis Path-Downstream 1~30

1
[ 110-52-1 ]
[ 70500-72-0 ]
[ 203395-59-9 ]

Yield	Reaction Conditions	Operation in experiment
86.5%	With potassium carbonate; In acetone; at 20℃; for 3h;Reflux;	At room temperature, add 0.82g (5.0mmol) of 7-hydroxy-2-quinolone to a 100ml reaction flask, and add 40ml of acetone. Add 1.38g (10.0mmol) of anhydrous potassium carbonate to start stirring,1,4-Dibromobutane was added dropwise with stirring, and the temperature was raised to reflux to hold the reaction for 3 hours, and the raw material disappeared by TLC (developing agent: ethyl acetate / petroleum ether = 1:1). After the reaction, the reaction solution was cooled to room temperature, and the insoluble solids were filtered off. The filter cake was rinsed with acetone and the filtrates were combined. The filtrate was evaporated to dryness under reduced pressure to obtain a light yellow oil. 40ml of petroleum ether was added to the oil, stirred and crystallized, filtered to obtain the target product, and dried at 40 C in the air to obtain 1.3g of white orange yellow solid with a yield of 86.5%.
41%	With potassium carbonate; In ethanol;Reflux;	Intermediate 14:[0130] AICI3 (11.5 g, 86.3 mmol) was added portion-wise to a suspension of intermediate 13 (4.2 g, 16.6 mmol) in chlorobenzene (90 mL) at 0C. The reaction mixture was gradually warmed to 120C and stirred for 3 h. The mixture was poured into ice water and the resulting precipitate was collected by filtration, washed with water, and purified by flash chromatography on silica gel column (elution with DCM/MeOH = 60:1) to give 7-hydroxyquinolin-2(lH)-one (intermediate 14) (1.41 g, 53%) as a white solid. Intermediate 15:
	With potassium hydroxide; In isopropyl alcohol; for 6h;Heating / reflux;	A mixture of 7-hydroxy-2(lH)-quinolinone (72; 6.44 g, 40 mmol), KOH (2.80 g, 50 rnniol), and 1,4-dibromobutane (73; 14.4 mL, 120 mmol) in isopropanol (180 mL) was heated under reflux conditions for 6 h. The solid was removed by filtration, and the filtrate was concentrated in vacuo. The residue was triturated with heptane to give the crude compound 74 (9.70 g, -70% purity by LCMS) as a reddish-brown solid.

Reference： [1]Patent: CN110776459,2020,A .Location in patent: Paragraph 0024
[2]Organic Process Research and Development,2018,vol. 22,p. 1471 - 1480
[3]Journal of Enzyme Inhibition and Medicinal Chemistry,2020,vol. 35,p. 118 - 128
[4]Patent: WO2012/3418,2012,A2 .Location in patent: Page/Page column 51
[5]Journal of Medicinal Chemistry,1998,vol. 41,p. 658 - 667
[6]Patent: WO2008/24481,2008,A2 .Location in patent: Page/Page column 42
[7]Journal of Medicinal Chemistry,2012,vol. 55,p. 7141 - 7153

2
[ 13339-01-0 ]
[ 203395-59-9 ]
7-{4-[4-(2-ethoxyphenyl)-1-piperazinyl]butoxy}carbostyril [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1998,vol. 41,p. 658 - 667

3
[ 1013-22-5 ]
[ 203395-59-9 ]
7-{4-[4-(2,3-Dimethyl-phenyl)-piperazin-1-yl]-butoxy}-1H-quinolin-2-one [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1998,vol. 41,p. 658 - 667

4
[ 54711-70-5 ]
[ 203395-59-9 ]
7-{4-[4-(3-Chloro-2-methyl-phenyl)-piperazin-1-yl]-butoxy}-1H-quinolin-2-one [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1998,vol. 41,p. 658 - 667

5
[ 41202-77-1 ]
[ 203395-59-9 ]
[ 129722-25-4 ]

Reference： [1]Journal of Medicinal Chemistry,1998,vol. 41,p. 658 - 667

6
1-(2-methyl-3-bromophenyl)piperazine [ No CAS ]
[ 203395-59-9 ]
7-{4-[4-(3-Bromo-2-methyl-phenyl)-piperazin-1-yl]-butoxy}-1H-quinolin-2-one [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1998,vol. 41,p. 658 - 667

7
[ 129722-34-5 ]
[ 203395-59-9 ]

Yield	Reaction Conditions	Operation in experiment
98.99%	With 2,3-dicyano-5,6-dichloro-p-benzoquinone; In tetrahydrofuran; at 20℃; for 12h;Inert atmosphere;	To a 500 mL two-neck round-bottom flask fitted with a magneticstir bar and argon inlet was charged <strong>[129722-34-5]7-[4-bromobutoxy]-3,4-dihydro-2(1H)-quinolinone</strong> 5b (10 g, 0.033 mol) in THF(200 mL). To the aforementioned mixture 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (30.4 g, 0.13 mol) was added and the contents were stirred at rt until the completion of the reaction.Upon the consumption of starting material (as indicatedby TLC), THF was evaporated under reduced pressure. Theresidual product obtained was washed with water (200 mL)and extracted with ethyl acetate (3 × 100 mL). The organiclayer was washed with brine, dried over anhydrous Na2SO4,and concentrated under reduced pressure to furnish the crudeproduct. The crude product was purified by column chromatographyusing Ethyl acetate and n-Hexane as solventsystem to afford the title compound 8b.Yield: 98.99% (9.8 g);1H NMR (400 MHz, DMSO-d6) delta 11.57 (s, 1H), 7.77 (d,J = 9.4 Hz, 1H), 7.53 (d, J = 9.4 Hz, 1H), 6.83-6.69 (m,2H), 6.27 (d, J = 9.6 Hz, 1H), 4.02 (t, J = 6.1 Hz, 2H), 3.59(t, J = 6.6 Hz, 2H), 2.03-1.89 (m, 2H), 1.89-1.74 (m, 2H);13C NMR (100 MHz, DMSO-d6): delta 162.67, 160.72, 141.05,140.44, 129.69, 118.97, 113.77, 111.19, 99.05, 67.28, 35.26,29.46, 27.74; ESI (MS): 296 [M+H]+; HPLC purity: 99.26%[RT: 11.545 min; UV detection at 210 nm; Column: X BridgeC-18, 150 × 4.6 mm, 5 mum particle size; Mobile phase: A)0.1% TFA in water, B) Acetonitrile; T/%B: 0/10, 3/10, 15/95,23/95, 25/10, 30/10; Flowrate: 1.0 mL/min;Diluent:Acetonitrile:Water (80:20)]. 1H NMR spectral data of 8b was foundto be consistent with the values reported in Ref. 16.

Reference： [1]Journal of Chemical Sciences,2018,vol. 130
[2]Journal of Organic Chemistry,2019,vol. 84,p. 8702 - 8709
[3]Synthetic Communications,2007,vol. 37,p. 4337 - 4341

8
[ 913734-73-3 ]
[ 203395-59-9 ]
[ 1314032-23-9 ]

Yield	Reaction Conditions	Operation in experiment
65%	With triethylamine; In acetonitrile;Inert atmosphere;	General procedure: A mixture of <strong>[203395-59-9]7-(4-bromobutoxy)quinolin-2(1H)-one</strong>17 (21, 0.78 mmol), 1-(2-methoxyphenyl)piperazine hydrochloride (1.00 mmol), and triethylamine (0.5 mL) in acetonitrile (15 mL) was refluxed overnight. The solvent was evaporated under reduced pressure. The residue was dissolved in dichloromethane, washed with saturated NaHCO3 solution, dried over Na2SO4, concentrated in vacuo. The resulting residue was purified by silica gel column chromatography (5% methanol in dichloromethane) to give the product as an oil (62% yield). Conversion to the oxalate salt gave 11 as an off-white powder.

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 3502 - 3511

9
[ 5464-78-8 ]
[ 203395-59-9 ]
7-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butoxy)quinolin-2(1H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	With triethylamine; In acetonitrile;Inert atmosphere;	A mixture of <strong>[203395-59-9]7-(4-bromobutoxy)quinolin-2(1H)-one</strong>17 (21, 0.78 mmol), 1-(2-methoxyphenyl)piperazine hydrochloride (1.00 mmol), and triethylamine (0.5 mL) in acetonitrile (15 mL) was refluxed overnight. The solvent was evaporated under reduced pressure. The residue was dissolved in dichloromethane, washed with saturated NaHCO3 solution, dried over Na2SO4, concentrated in vacuo. The resulting residue was purified by silica gel column chromatography (5% methanol in dichloromethane) to give the product as an oil (62% yield). Conversion to the oxalate salt gave 11 as an off-white powder, mp 180-182 C; 1H NMR (free base, CDCl3) delta 12.30 (s, 1H), 7.71-7.74 (m, 1H), 7.42-7.45 (m, 1H), 6.78-7.02 (m, 6H), 6.53-6.56 (m, 1H), 4.07-4.10 (m, 2H), 3.86 (s, 3H), 3.11 (br s, 4H), 2.68 (br s, 4H), 2.47-2.52 (m, 2H), 1.72-1.90 (m, 4H). HRMS calcd for C24H30N3O3 [M+H]+ 408.2287, found: 408.2290.

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 3502 - 3511

10
[ 536-90-3 ]
[ 203395-59-9 ]

Reference： [1]Patent: WO2012/3418,2012,A2
[2]Journal of Enzyme Inhibition and Medicinal Chemistry,2020,vol. 35,p. 118 - 128

11
[ 98224-03-4 ]
[ 203395-59-9 ]
[ 1354030-75-3 ]

Yield	Reaction Conditions	Operation in experiment
50%		Compound 42:[0216] A mixture of intermediate 15 (70 mg, 0.24 mmol) and Nal (70 mg, 0.48 mmol) in CH3CN was heated to reflux for 30 min and then cooled to rt. Intermediate 61 (78 mg, 0.36 mmol) and anhydrous K2C03 (162 mg, 0.96 mmol) were added to the mixture. The resulting mixture was heated to reflux and stirred for 4 h. Precipitated crystals were filtered off and the filtrate was evaporated under reduced pressure. The residue was extracted with EtOA. The combined EtOAc layers were washed with brine, dried over anhydrous Na2S04, concentrated in vacuo and purified by flash chromatography on silica gel column (elution with DCM/MeOH = 30:1) to give 7-(4-(4-(2,3-dihydrobenzo[b][l,4]dioxin-5-yl)piperazin-l-yl)butoxy)quinolin- 2(lH)-one (compound 42) (52 mg, 50%). .H NMR (300 MHz, CDC13): delta 11.65 (brs, 1H), 7.72 (d, J = 9.6 Hz, 1H), 7.45 (d, J = 8.4 Hz, 1H), 6.82-6.75 (m, 3H), 6.61- 6.52 (m, 3H), 4.33-4.26 (m, 4H), 4.12-4.08 (m, 2H), 3.12 (br, 4H), 2.70 (br, 4H), 2.52(br, 2H), 2.04-1.68 (m, 6H). HPLC: 99%, RT 2.167 min. MS (ESI) m/z 436.0 [M + H]+.

Reference： [1]Patent: WO2012/3418,2012,A2 .Location in patent: Page/Page column 99

12
hexahydro-1-(2-methoxyphenyl)-1 H-1,4-diazepine monohydrochloride [ No CAS ]
[ 203395-59-9 ]
[ 1354030-31-1 ]

Yield	Reaction Conditions	Operation in experiment
26%		Compound 10:[0152] A mixture of intermediate 15 (150 mg, 0.51 mmol) and Nal (150 mg, 1.02 mmol) in CH3CN was heated to reflux for 30 min and then cooled to rt. Intermediate 29 (124 mg, 0.51 mmol) and anhydrous K2C03 (282 mg, 2.04 mmol) were added to the mixture. The resulting mixture was heated to reflux and stirred overnight. The reaction solution was diluted with water and extracted with EtOAc. The combined EtOAc layers were washed with brine, dried Over anhydrous Na2S04, concentrated in vacuo and purified by flash chromatography on silica gel column (elution with DCM/MeOH = 30: 1) to give 7-(4-(4-(2-methoxyphenyl)-l,4-diazepan-l- yl)butoxy)quinolin-2(lH)-one (compound 10) (61 mg, 26%). *H NMR (300 MHz, CDC13) delta 7.69 (d, J = 9.6 Hz, 1H), 7.43 (d, J= 8.7 Hz, 1H), 6.91-6.85 (m, 5H), 6.79 (d, J= 9.0 Hz, 1H), 6.65 (s, 1H) 6.49 (d, J= 9.3 Hz, 1H), 4.07 (t, J = 6.0 Hz, 2H), 3.83 (s, 3H), 3.34-3.29 (m, 4H), 2.93-2.86 (m, 4H), 2.69-2.65 (m, 2H), 2.06-2.02 (m, 2H), 1.86-1.84 (m, 2H), 1.77-1.73 (m, 2H). HPLC: 95%, RT 1.902 min. MS (ESI) m/z 422.3 [M + H]+.

Reference： [1]Patent: WO2012/3418,2012,A2 .Location in patent: Page/Page column 61

13
[ 15116-41-3 ]
[ 203395-59-9 ]

Reference： [1]Patent: WO2012/3418,2012,A2

14
[ 839712-09-3 ]
[ 203395-59-9 ]
[ 1354030-20-8 ]

Yield	Reaction Conditions	Operation in experiment
26%		Compound 4:[0132] A mixture of intermediate 15 (120 mg, 0.41 mmol) and al (123 mg, 0.82 mmol) in C¾CN was heated to reflux for 30 min and then cooled to rt. Intermediate 2 (175 mg, 0.62 mmol) and anhydrous K2C03 (226 mg, 1.64 mmol) were added to the mixture. The resulting mixture was heated to reflux overnight. The mixture was evaporated under reduced pressure and the residue was extracted with EtOAc. The combined EtOAc layers were washed with brine, dried over anhydrous Na2S04, concentrated in vacuo and purified by flash chromatography on silica gel column (elution with DCM/MeOH = 30:1) to give 7-(4-(4-(2,3-dichlorophenyl)-l,4- diazepan-l-yl)butoxy)quinolin-2(lH)-one (compound 4) (50 mg, 26%). NMR (300 MHz, CDC13) delta 11.54 (br? 1H), 7.71 (d, J = 6.9 Hz, 1H) 7.44 (d, J = 8.1 Hz, 1H), 7.09-7.07 (m, 2H), 7.01-6.97 (m, 1H), 6.82-6.78 (m, 2H), 6.53 (d, J= 9.3 Hz, 1H), 4.10 (t, J= 6.6 Hz, 2H), 3.30 (d, J = 5.1 Hz, 4H), 2.87-2.81 (m, 4H), 2.62 (t, J= 7.5 Hz, 2H), 2.01-1.99 (m, 2H), 1.92-1.82 (m, 2H), 1.76-1.68 (m, 2H). HPLC: 99%, RT 2.461 min. MS (ESI) m/z 460.2 [M + H]+. mp: 55-57C.

Reference： [1]Patent: WO2012/3418,2012,A2 .Location in patent: Page/Page column 51
[2]Journal of Medicinal Chemistry,2012,vol. 55,p. 7141 - 7153

15
[ 1354030-34-4 ]
[ 203395-59-9 ]
[ 1354030-37-7 ]

Yield	Reaction Conditions	Operation in experiment
24%		Compound 14:[0158] A mixture of intermediate 15 (150 mg, 0.51 mmol) and Nal (150 mg, 1.0 mmol) in CH3CN was heated to reflux for 30 min and then cooled to rt. Intermediate 31 (130 mg, 0.51 mmol) and anhydrous K2C03 (282 mg, 2.04 mmol) were added to the mixture. The resulting mixture was heated to reflux and stirred overnight. The reaction solution was diluted with water and extracted with EtOAc. The combined EtOAc layers were washed with brine, dried over anhydrous Na2S04, concentrated in vacuo and purified by flash chromatography on silica gel column (elution with DCM/MeOH = 50:1) to give 7-(4-(4-(2-ethoxyphenyl)-l,4-diazepan-l- yl)butoxy)quinolin-2(lH)-one (compound 14) (50 mg, 24%). lH NMR (300 MHz, CDC13) delta 10.89 (bs, 1H), 7.69 (d, J= 9.6 Hz, 1H), 7.44 (d, J= 9.0 Hz, 1H), 6.92-6.78 (m, 5H), 6.71 (d, J =2.7 Hz, 1H), 6.51 (d, J=9.6 Hz, 1H), 4.10-4.01 (m, 4H), 3.36-3.30 (m, 4H), 2.89-2.79 (m, 4H), 2.62-2.59 (m, 4H), 2.02-2.01 (m, 2H), 1.89-1.82 (m, 2H), 1.45 (t, J= 6.9 Hz, 3H). HPLC: 99%, RT 2.375 min. MS (ESI) m/z 436.2 [M + H]+.

Reference： [1]Patent: WO2012/3418,2012,A2 .Location in patent: Page/Page column 65

16
[ 1354030-40-2 ]
[ 203395-59-9 ]
[ 1354030-42-4 ]

Yield	Reaction Conditions	Operation in experiment
62%		Compound 18:[0165] A mixture of intermediate 15 (120 mg, 0.41 mmol) and Nal (123 mg, 0.82 mmol) in CH3CN was heated to reflux for 30 min and then cooled to rt. Intermediate 34 (111 mg, 0.41 mmol) and anhydrous K2C03 (226 mg, 1.64 mmol) were added to the mixture. The resulting mixture was heated to reflux and stirred overnight. The reaction solution was diluted with water and extracted with EtOAc. The combined EtOAc layers were washed with brine, dried over anhydrous Na2S04, concentrated in vacuo and purified by flash chromatography on silica gel column (elution with DCM/MeOH = 50:1) to give 7-(4-(4-(2-isopropoxyphenyl)-l,4-diazepan-l- yl)butoxy)quinolin-2(lH)-one (compound 18) (115 mg, 62%). 1H NM (300 MHz, CDC13) delta 11.68 (bs., 1H), 7.71 (d, J= 9.3 Hz, 1H), 7.44 (d, J= 9.3 Hz, 1H), 6.89-6.79 (m, 6H), 6.53 (d, J= 9.6 Hz, 1H), 4.62-4.54 (m, 1H), 4.11-4.07 (m, 2H), 3.34-3.29 (m, 4H), 2.94-2.86 (m, 4H), 2.72- 2.62 (m, 2H), 2.12-1.96 (m, 2H), 1.87-1.76 (m, 4H), 1.35 (d, J= 6.0 Hz, 6H). HPLC: 99%, RT 2.434 min. MS (ESI) m/z 450.3 [M + H]+.

Reference： [1]Patent: WO2012/3418,2012,A2 .Location in patent: Page/Page column 69

17
1-(2,3-dichlorophenyl)-piperazine hydrochloride [ No CAS ]
[ 203395-59-9 ]
[ 129722-25-4 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 7141 - 7153

18
1-benzo[b]thiophen-4-ylpiperazine hydrochloride [ No CAS ]
[ 203395-59-9 ]
[ 913611-97-9 ]

Yield	Reaction Conditions	Operation in experiment
21 g	With potassium carbonate; sodium iodide; In acetonitrile;Reflux;	Compound 1c (17.5g, 59 . 12mmol), 1 - (Benzothiophen-4-yl) piperazine hydrochloride (17.3g, 67 . 98mmol), potassium carbonate (20.7g, 150mmol), sodium iodide (1.33g, 8 . 87mmol) into the reaction bottle, by adding 500 ml acetonitrile, reflux reaction, to be TLC detection after the reaction, the solvent is concentrated under reduced pressure, water addition, pulping, filtering, the filter cake washing, with b the nitrile is heavy crude crystalline, filtering, drying, the white solid obtained 21g, i.e. target object [...] (1a-1), HPLC purity > 99%.

Reference： [1]Patent: CN105859703,2016,A .Location in patent: Paragraph 0214; 0215; 0217

19
[ 37783-33-8 ]
[ 203395-59-9 ]

Yield	Reaction Conditions	Operation in experiment
29.6 g	With 2,3-dicyano-5,6-dichloro-p-benzoquinone; In 1,4-dioxane; at 95℃; for 2h;	Compound 2c (30g, 100.67mmol), DDQ (25.1g, 110 . 57mmol) into 1L reaction bottle, by adding 1,4-dioxane 300 ml, stirring under 95 C 2 hours, TLC monitoring reaction is ended, concentrated under reduced pressure, by adding ice water, then adding sodium thiosulfate aqueous solution, stirring, add 3L dichloromethane extraction, separating the organic layer, an organic layer saturated salt water for washing, drying of anhydrous sodium sulfate, filtered, concentrated to obtain 29.6g strawcoloured solid 1c, almost quantitative yield, directly without further purification in the next step.

Reference： [1]Patent: CN105859703,2016,A .Location in patent: Paragraph 0214; 0215; 0216

20
1-(benzo[b]thiophen-4-yl)piperazine dihydrochloride [ No CAS ]
[ 203395-59-9 ]
[ 913611-97-9 ]

Yield	Reaction Conditions	Operation in experiment
85%		1-(Benzo[b]thiophen-4-yl)piperazinedihydrochloride (7·2HCl) (282 mg, 0.97 mmol) indryDMFwas taken in a 100 mL two-neck round-bottom flaskfitted with a magnetic stir bar and argon inlet. To this reactionmixture,K2CO3 (488 mg, 3.53 mmol)was added and the reactionwas allowed to stir at rt for 30 min. One mole equivalentof KI (167 mg, 1.01 mmol) and 7-(4-bromobutoxy)quinolin-2(1H)-one 8b (300 mg, 1.01 mmol) were added consecutively.The contents were heated at 100 C for 4 h. Upon completeconsumption of starting material (as indicated by TLC), thereaction mixture was cooled to 0 C, then 5 mL of waterwas added and stirred for 30 min. The resultant precipitate(off-white solid) observed was filtered using sintered funnel,redissolved in a mixture of MeOH and CH2Cl2 and subjectedto column chromatography (100-200 mesh) using 3% MeOHin CH2Cl2 as solvent system to furnish the pure product Brexpiprazole1 as a white solid. Yield: 85% (357 mg); 1H NMR(400 MHz, DMSO-d6): delta 11.60 (s, 1H), 7.79 (d, J = 9.4 Hz,1H), 7.67 (d, J = 5.5 Hz, 1H), 7.59 (d, J = 8.1 Hz, 1H),7.54 (d, J = 9.0 Hz, 1H), 7.37 (d, J = 5.7 Hz, 1H), 7.25 (t,J = 7.9 Hz, 1H), 6.85 (d, J = 7.7 Hz, 1H), 6.82-6.73 (m,2H), 6.28 (d, J = 9.4 Hz, 1H), 4.03 (t, J = 6.4 Hz, 2H), 3.04(brs, 4H), 2.62 (brs, 4H), 2.44 (t, J = 6.9 Hz, 2H), 1.84-1.70(m, 2H), 1.70-1.53 (m, 2H); 13C NMR (100 MHz, DMSOd6):delta 162.73, 160.89, 148.62, 141.09, 140.85, 140.49, 133.80,129.69, 126.28, 125.53, 122.33, 118.89, 117.11, 113.72, 112.47, 111.32, 99.03, 68.04, 57.74, 53.36, 52.05, 26.98,23.06; ESI (MS): 434 [M+H]+; HPLC purity: 97.97% [RT:10.504 min; UV detection at 215 nm; Column: X-Terra RP18, 150 × 4.6 mm, 5 mum particle size; Mobile phase: A)0.1% TFA in water B) Acetonitrile; T/%B: 0/20, 3/20, 12/95,23/95, 25/20, 30/20; Flowrate: 1.0 mL/min;Diluent:Acetonitrile:Water (80:20)]. 1H NMR spectral data of 1 was found tobe consistent with the values reported in Ref. 9.

Reference： [1]Journal of Chemical Sciences,2018,vol. 130

21
[ 70500-72-0 ]
[ 203395-59-9 ]
7-(4-(2-oxo-1,2-dihydroquinolin-7-oxy)butoxy)quinolin-2(1H)-one [ No CAS ]

Reference： [1]Organic Process Research and Development,2019,vol. 23,p. 852 - 857

22
[ 110-89-4 ]
[ 75-15-0 ]
[ 203395-59-9 ]
4-((2-oxo-1,2-dihydroquinolin-7-yl)oxy)butyl piperidine-1-carbodithioate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79.8%		At room temperature,In a 50 ml reaction flask, add 10 ml of N,N-dimethylformamide, add 0.10 g (1 mmol) of triethylamine, and add 0.08 g (1 mmol) of piperidine. Start stirring and add 0.08g (1.1mmol) of carbon disulfide. After stirring for 10 minutes, add 10ml N,N-dimethylformamide dissolved 7- (4-bromobutoxy)quinolin-2-one (Compound 2) g (1mmol), react at room temperature for 8 hours, After the reaction was completed by TLC detection, the reaction solution was evaporated to dryness to obtain an off-white solid, which was purified by silica gel column chromatography to obtain the target compound I-c 0.30g, yield 79.8%.

Reference： [1]Journal of Enzyme Inhibition and Medicinal Chemistry,2020,vol. 35,p. 118 - 128
[2]Patent: CN110776459,2020,A .Location in patent: Paragraph 0024

23
[ 626-58-4 ]
[ 75-15-0 ]
[ 203395-59-9 ]
4-((2-oxo-1,2-dihydroquinolin-7-yl)oxy)butyl 4-methylpiperidine-1-carbodithioate [ No CAS ]