124467-36-3|2-Chloro-7,8-dihydroquinolin-5(6H)-one| Ambeed

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Quality Control of [ 124467-36-3 ] Purity: 97% SDS Specification

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Product Details of [ 124467-36-3 ]

CAS No. :	124467-36-3
Formula :	C₉H₈ClNO
M.W :	181.62
SMILES Code :	O=C1C2=C(N=C(Cl)C=C2)CCC1
MDL No. :	MFCD08692066
InChI Key :	GWDDFDLEOYOZLY-UHFFFAOYSA-N
Pubchem ID :	592839

Safety of [ 124467-36-3 ]

GHS Pictogram:
Signal Word:	Danger
Hazard Statements:	H302-H315-H318-H335-H410
Precautionary Statements:	P261-P273-P280-P305+P351+P338
Class:	8
UN#:	1759
Packing Group:	Ⅲ

Computational Chemistry of [ 124467-36-3 ] Show Less

Physicochemical Properties

Num. heavy atoms	12
Num. arom. heavy atoms	6
Fraction Csp3	0.33
Num. rotatable bonds	0
Num. H-bond acceptors	2.0
Num. H-bond donors	0.0
Molar Refractivity	47.1
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.	1.88
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	1.95
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.25
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.	1.35
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	3.12
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.11

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.56
Solubility	0.495 mg/ml ; 0.00273 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.	-2.2
Solubility	1.14 mg/ml ; 0.00625 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	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	-3.64
Solubility	0.0418 mg/ml ; 0.00023 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.	-6.02 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	1.0 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)	2.09

Application In Synthesis of [ 124467-36-3 ]

* 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 [ 124467-36-3 ]

[ 124467-36-3 ] Synthesis Path-Downstream 1~35

1
[ 124467-36-3 ]
[ 124467-37-4 ]

Yield	Reaction Conditions	Operation in experiment
64%	With hydrogen bromide; bromine; In dichloromethane; at 20℃;	To a solution of <strong>[124467-36-3]2-chloro-7,8-dihydroquinolin-5(6H)-one</strong> (2 g, 11.2 mmol) in HBr (20 mL)was added Br2 (1.79 g, 11.2 mmol) in DCM (20 mL) at RT and stined for 2 h at the sametemperature. The reaction was quenched with ice-water, extracted with ethyl acetate. The organic portion was dried over anhydrous sodium sulphate, filtered and concentrated to get the title compound (1.8 g, 64%). LC-MS: 260.1 [M], 262.1 [M+2H].
	With bromine; potassium carbonate; In chloroform;	The latter compound (2 g) was dissolved in chloroform (200 ml) and treated with bromine (0.53 ml) dropwise at room temperature. After 30 min solid potassium carbonate was added, the mixture was stirred for 1 hour, filtered and solvent removed to give 2-chloro-6-bromo-7,8-dihydro-5-quinolinone (2.86 g).

References: [1]Patent: WO2016/185342,2016,A1 .Location in patent: Page/Page column 68.
[2]Patent: US5114940,1992,A .

2
[ 124467-36-3 ]
[ 536-74-3 ]
[ 864224-08-8 ]

Yield	Reaction Conditions	Operation in experiment
15%	With triethylamine;tetrakis(triphenylphosphine) palladium(0); for 3h;Heating / reflux;	To a solution of <strong>[124467-36-3]2-chloro-7,8-dihydro-6H-quinolin-5-one</strong> (0.2 g, 1.1 mmol) and ethynylbenzene (0.17 g, 1.6 mmol) in triethylamine (7 ml) under an argon atmosphere was added tetrakis (triphenylphosphine) palladium (0.02 g, 0.062 mmol). The mixture was heated at reflux for 3 h. Then it was concentrated under reduced pressure and the residue was purified by column chromatography on silica gel to give the title compound (0.04 g, 15%). Physical characteristics are as follows:Mp 121-122 0C; 1H NMR (CDCI3, TMS) delta: 2.20 (2H); 2.68 (2H); 3.17 (2H);7.22-7.38 (3H); 7.46 (1H); 7.60 (2H); 8.24 (1 H); MS 248 (M+1).
15%	With triethylamine;tetrakis(triphenylphosphine) palladium(0); for 3h;Heating / reflux;	To a solution of <strong>[124467-36-3]2-chloro-7,8-dihydro-6H-quinolin-5-one</strong> (0.2 g, 1.1 mmol) and ethynylbenzene (0.17 g, 1.6 mmol) in triethylamine (7 ml) under an argon atmosphere was added tetrakis (triphenylphosphine) palladium (0.02 g, 0.062 mmol). The mixture was heated at reflux for 3 h. Then it was concentrated under reduced pressure and the residue was purified by column chromatography on silica gel to give the title compound (0.04 g, 15%). Physical characteristics are as follows: Mp 121-122 0C; 1H NMR (CDCI3, TMS) delta: 2.20 (2H); 2.68 (2H); 3.17 (2H);7.22-7.38 (3H); 7.46 (1 H); 7.60 (2H); 8.24 (1 H); MS 248 (M+1 ).
15%	tetrakis(triphenylphosphine)palladium (0); In triethylamine;	EXAMPLE 1 2-Phenylethynyl-7,8-dihydro-6H-quinolin-5-one To a solution of <strong>[124467-36-3]2-chloro-7,8-dihydro-6H-quinolin-5-one</strong> (0.2 g, 1.1 mmol) and ethynylbenzene (0.17 g, 1.6 mmol) in triethylamine (7 ml) under an argon atmosphere was added tetrakis (triphenylphosphine) palladium (0.02 g, 0.062 mmol). The mixture was heated at reflux for 3 h. Then it was concentrated under reduced pressure and the residue was purified by column chromatography on silica gel to give the title compound (0.04 g, 15%). Physical characteristics are as follows: Mp 121-122 C.; 1H NMR (CDCl3, TMS) delta: 2.20 (2H); 2.68 (2H); 3.17 (2H); 7.22-7.38 (3H); 7.46 (1H); 7.60 (2H); 8.24 (1H); MS 248 (M+1).

References: [1]Patent: WO2007/23290,2007,A1 .Location in patent: Page/Page column 30.
[2]Patent: WO2007/23242,2007,A1 .Location in patent: Page/Page column 30.
[3]Patent: US2005/288284,2005,A1 .
[4]Journal of Medicinal Chemistry,2008,vol. 51,p. 634 - 647.

3
[ 124467-36-3 ]
1,3-diphenyl-1H-pyrazole-5-boronic acid [ No CAS ]
2-(2,5-diphenyl-2H-pyrazol-3-yl)-7,8-dihydro-6H-quinolin-5-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
5%	With triethylamine;tetrakis(triphenylphosphine) palladium(0); In toluene;Heating / reflux;	2-(2,5-Diphenyl-2H-pyrazol-3-yl)-7,8-dihydro-6H-quinolin-5-one[0095] To a solution of <strong>[124467-36-3]2-chloro-7,8-dihydro-6H-quinolin-5-one</strong> (0.2 g, 1.1 mmol) and 1 ,3-diphenyl-1 H-pyrazole-5-boronic acid (1.6 mmol) in triethylamine (7 ml) and toluene under an argon atmosphere was added tetrakis (triphenylphosphine) palladium (0.02 g, 0.062 mmol). The mixture was EPO <DP n="53"/>heated at reflux over night. Then it was concentrated under reduced-pressure and the residue was purified by column chromatography on silica gel to give the title compound (5 %).

References: [1]Patent: WO2007/23245,2007,A1 .Location in patent: Page/Page column 51-52.

4
[ 1945-84-2 ]
[ 124467-36-3 ]
2-pyridin-2-ylethynyl-7,8-dihydro-6H-quinolin-5-one [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 634 - 647.

5
[ 124467-36-3 ]
[ 92-54-6 ]
[ 864225-58-1 ]

References: [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 634 - 647.

6
[ 15450-69-8 ]
[ 124467-36-3 ]

Yield	Reaction Conditions	Operation in experiment
96%	With trichlorophosphate; In acetonitrile; at 75℃; for 1.25h;Inert atmosphere;	Example 3A 2-Chloro-7,8-dihydroquinolin-5(6H)-one Under nitrogen, 21.02 g (0.13 mol) of 7,8-dihydroquinoline-2,5(1H,6H)-dione were suspended in 100 ml of acetonitrile (anhydrous, <30 ppm H2O), and 135.28 ml (density 1.46 g/ml, 1.29 mol) of phosphorus oxychloride were added. The yellowish suspension was then heated to 75 C. and stirred at this temperature for 1.25 hours. The yellow clear solution was then cooled to room temperature, and 150 ml of toluene were added. The solution was then concentrated on a rotary evaporator to about 100 ml, and another 150 ml of toluene were added. The solution was then concentrated to dryness on a rotary evaporator. 300 ml of ethyl acetate were then added to the orange oil obtained. Subsequently, the solution was carefully (evolution of gas) added to 500 ml of saturated aqueous sodium bicarbonate solution and stirred for 15 min. The phases were separated and the aqueous phase was extracted with 200 ml of ethyl acetate. The combined organic phases were washed twice with 250 ml of water and once with 100 ml of saturated sodium chloride solution, dried over sodium sulphate, filtered and concentrated to dryness under reduced pressure. This gave 22.58 g (0.12 mmol, 96% of theory) of the target compound as a slightly yellowish solid. 1H-NMR (400 MHz, DMSO-d6, delta/ppm): 2.06-2.17 (m, 2H), 2.61-2.70 (m, 2H), 3.05 (t, 2H), 7.51 (d, 1H), 8.18 (d, 1H).
90.9%	With trichlorophosphate; In acetonitrile; for 2h;Reflux;	To a solution of 7,8-dihydroquinoline-2,5(1H,6H)-dione (5 g, 27.6 mmol ) in acetonitrile(50 mL) was added POC13 (12.6 g, 82.5 mmol) dropwise at 0 C. The cooling bath was removedand the reaction mixture was refluxed for 2h. The reaction mixture was cooled to room temperature and the volatiles were evaporated under reduced pressure to get the residue, which was neutralized with ammonium hydroxide and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and concentrated to get the title compound (5 g, 90.9%).LC-MS: 181.9 [M+H].
74%		3.2 2-Chloro-7,8-dihydroquinolin-5(6H)-oneTo a suspension of 7,8-dihydroquinoline-2,5(1H,6H)-dione (1.5 g, 9.19 mmol) in acetonitrile (22 mL) was added dropwise phosphorous oxychloride (1.714 mL, 18.39 mmol). The resulting solution was heated to 100 C. and stirred for 2 h. The reaction was cooled to RT and poured into ice-cold water. After basifying the mixture with 2 M sodium hydroxide solution it was extracted with ethyl acetate (3×). After each extraction the pH of the aqueous phase was checked and if necessary adjusted by adding 1 M sodium hydroxide solution. The combined organic layers were dried over sodium sulfate, filtered, and evaporated to dryness. The crude was purified by flash chromatography (silica gel, cyclohexane/ethyl acetate) yielding a colourless solid. Amount 1.23 g. Yield 74%.1H-NMR (DMSO-d6, 400 MHz) delta 2.13 (m, 2H), 2.68 (m, 2H), 3.08 (t, 2H), 7.53 (d, 1H), 8.20 (d, 1H)MS (ES-API) m/z 182.0 (M+H+, 100%).

66%	With trichlorophosphate; at 90℃; for 0.666667h;	Example 7 (+-)-[2-(2,6-Diethyl-phenyl)-5,6,7,8-tetrahydro-quinolin-5-yl]-ethyl-naphthlen-1-yl-amine (Compound #109) 7,8-Dihydro-1H,6H-quinoline-2,5-dione (101 mg, 0.621 mmol, 1 equiv) was treated with POCl3 (1.0 mL, 10.9 mmol, 18 equiv) and the resulting suspension was heated in a 90 C. oil bath for 40 minutes. The resulting mixture was concentrated and the residue was poured into ice (5 mL). The resulting suspension was neutralized to pH 7 by addition of solid Na2CO3 and was extracted with CH2Cl2 (3*5 mL). The organic phase was washed with water (15 mL), then was dried (Na2SO4), filtered, and concentrated. The residue was purified by flash column chromatography (SiO2, 0-20% EtOAc in hexanes) to yield 2-chloro-7,8-dihydro-6H-quinolin-5-one as a white solid (74.3 mg, 66%). 1H NMR (300 MHz, CDCl3) delta 8.23 (d, 1H), 7.31 (d, 1H), 3.14 (t, 2H), 2.69 (t, 2H), 2.20 (quint, 2H); MS m/z (MH+) 182.1.
		To 200 mg (1.23 mmol) of 7,8-dihydroquinoline-2,5(1H,6H)-dione in acetonitrile (6.1 mL) was added 1.14 mL (12.3 mmol) of phosphorous oxychloride and the mixture was heated at 65 C. for 3 hours. The reaction was cooled to room temperature and the excess phosphorous oxychloride was removed via rotary evaporation. The residue was partitioned between EtOAc (400 mL) and water (200 mL) and the organic phase was washed sequentially with saturated NaHCO3 (200 mL) and brine (200 mL). The organic phase was dried over MgSO4 and concentrated to afford N-1 as a beige solid. Data for N-1: LC/MS: rt=1.64 min; m/z (M+H)=182.1 found; 182.0 required.
630 mg	With trichlorophosphate; In acetonitrile; at 100℃; for 3h;	Step 2: 2-Chloro-7,8-dihydro-6H-quinolin-5-one. 7,8-Dihydro-1 H,6H-quinoline-2,5-dione (1 .1 g, 6.74 mmol) is dissolved in acetonitrile (25 ml), phosphorus oxychloride (1 .26 ml, 13.5 mmol) is added dropwise and the mixture is stirred at 100C for 3 hours. The mixture is cooled to 0C and poured into cold water, NaOH 2M aq. solution is added until pH >7 is reached, then the mixture is extracted with dichloromethane (3 x 30 ml), the combined organic layers are dried over sodium sulphate, filtered and concentrated. The residue is purified by flash chromatography (0 - 20% ethyl acetate in cyclohexane) to give the title compound (Yield 630 mg). LC (Method 1 ): tR = 2.61 min; Mass spectrum (ES+): m/z = 182 [M+H]+.
13 g	With trichlorophosphate; In acetonitrile;Reflux;	S8. 20 g of compound P16015-2 was added to 200 mL+, and 98 g of phosphorus oxychloride was added dropwise to the reaction solution through a constant pressure dropping funnel; after the dropwise addition was completed, the temperature was raised to reflux, and the reaction was stirred overnight. After completion of the reaction, the mixture was concentrated under reduced vacuo.S9. The organic phase is washed with a saturated aqueous solution of sodium carbonate to a weak basic. The organic phase was washed three times with a saturated aqueous solution of sodium chloride and then evaporated.S10. The crude solid was recrystallized using EA/PE = 1:2 solvent system to give a solid. Solid product using vacuum dried soil Yellow product 13g

References: [1]Patent: US2014/31391,2014,A1 .Location in patent: Paragraph 0368; 0369; 0370.
[2]Patent: WO2016/185342,2016,A1 .Location in patent: Page/Page column 52; 53; 54.
[3]Patent: US2012/77840,2012,A1 .Location in patent: Page/Page column 75.
[4]Patent: US2009/48295,2009,A1 .Location in patent: Page/Page column 30.
[5]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 240 - 244.
[6]Journal of Medicinal Chemistry,2008,vol. 51,p. 634 - 647.
[7]Patent: US2008/132490,2008,A1 .Location in patent: Page/Page column 21.
[8]Patent: WO2017/72020,2017,A1 .Location in patent: Page/Page column 65.
[9]Patent: CN108218770,2018,A .Location in patent: Paragraph 0056; 0073-0080.

7
[ 124467-36-3 ]
[ 610286-39-0 ]
[ 1119227-47-2 ]

Yield	Reaction Conditions	Operation in experiment
71%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; toluene; for 28h;Heating / reflux;	To a mixture of <strong>[124467-36-3]2-chloro-7,8-dihydro-6H-quinolin-5-one</strong> (68.8 mg, 0.379 mmol, 1 equiv), 2,6-diethylphenylboronic acid (70.8 mg, 0.398 mmol, 1.05 equiv) and Pd(PPh3)4 (21.9 mg, 18.9 mumol, 0.05 equiv) was added 2 M aqueous Na2CO3 (1 mL) and toluene (1 mL). The resulting mixture was heated at reflux under nitrogen for 1 d. Analysis of a sample of the reaction mixture by LCMS indicated incomplete conversion, so additional portions of 2,6-diethylphenylboronic acid, Pd(PPh3)4, 2 M aqueous Na2CO3, and toluene (amounts as above) were added and the resulting mixture was heated at reflux for an additional 4 h. The mixture was then partitioned between EtOAc (20 mL) and water (20 mL). The separated aqueous phase was extracted with two additional 20-mL portions of EtOAc. The organic extracts were dried (Na2SO4) and filtered, and the filtrate was concentrated. The resulting residue was purified by flash column chromatography (SiO2, 0-20% EtOAc in hexanes) to yield 2-(2,6-diethyl-phenyl)-7,8-dihydro-6H-quinolin-5-one (75.1 mg, 71%). 1H NMR (300 MHz, CDCl3) delta 8.34 (d, 1H), 7.23-7.34 (m, 2H), 7.15 (d, 2H), 3.21 (t, 2H), 2.75 (t, 2H), 2.33 (q, 4H), 2.26 (quint, 2H), 1.05 (t, 6H); MS m/z (MH+) 280.3.

References: [1]Patent: US2009/48295,2009,A1 .Location in patent: Page/Page column 30.

8
[ 124467-36-3 ]
[ 1241496-36-5 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 240 - 244.

9
[ 124467-36-3 ]
C₂₂H₂₅ClN₂O₂ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 240 - 244.

10
[ 124467-36-3 ]
C₁₅H₁₉ClN₂O₂ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 240 - 244.

11
[ 124467-36-3 ]
C₂₀H₂₇ClN₂O₄ [ No CAS ]
C₂₀H₂₇ClN₂O₄ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 240 - 244.

12
[ 124467-36-3 ]
C₁₈H₂₃ClN₂O₄ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 240 - 244.

13
[ 124467-36-3 ]
C₁₈H₂₂Cl₂N₂O₃ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 240 - 244.

14
[ 124467-36-3 ]
C₃₅H₄₆ClN₃O₃ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 240 - 244.

15
[ 124467-36-3 ]
C₃₆H₄₉N₃O₃ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 240 - 244.

16
[ 124467-36-3 ]
[ 867-13-0 ]
C₁₃H₁₄ClNO₂ [ No CAS ]
C₁₃H₁₄ClNO₂ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 240 - 244.

17
[ 5220-49-5 ]
[ 124467-36-3 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 240 - 244.
[2]Patent: US2012/77840,2012,A1 .
[3]Patent: US2014/31391,2014,A1 .
[4]Patent: WO2017/72020,2017,A1 .

18
[ 124467-36-3 ]
[ 61394-50-1 ]
2-Hydroxy-3-(5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)-1H-indole-5-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
20%	With sodium hexamethyldisilazane; In tetrahydrofuran; at 110℃; for 0.166667h;Microwave irradiation;	3.3 2-Hydroxy-3-(5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)-1H-indole-5-carbonitrileTo a suspension of <strong>[124467-36-3]2-chloro-7,8-dihydroquinolin-5(6H)-one</strong> (50 mg, 0.275 mmol) and 2-oxoindoline-5-carbonitrile (45.7 mg, 0.289 mmol) in tetrahydrofuran (1.4 mL) was added a 1.0 M solution of sodium bis(trimethylsilyl)amide (641 muL, 0.641 mmol). The mixture was stirred for 3 min at RT and then heated in a microwave oven to 110 C. for 10 min. After cooling to RT the reaction was quenched by addition of methanol (1 mL). The resulting solution was evaporated to dryness. The crude was purified by flash chromatography (silica gel, dichloromethane/methanol) yielding an orange solid. Amount 17 mg. Yield 20%.1H-NMR (DMSO-d6, 400 MHz) delta 2.17 (m, 2H), 2.59 (t, 2H), 3.08 (t, 2H), 7.06 (d, 1H), 7.38 (dd, 1H), 7.68 (d, 1H), 7.98 (m, 2H), 11.11 (s, 1H), 14.78 (bs, 1H)MS (ES-API) m/z 304 (M+H+, 100%).

References: [1]Patent: US2012/77840,2012,A1 .Location in patent: Page/Page column 75.

19
[ 124467-36-3 ]
[ 1429914-13-5 ]

References: [1]Patent: WO2013/52394,2013,A1 .

20
[ 124467-36-3 ]
[ 1429914-14-6 ]

References: [1]Patent: WO2013/52394,2013,A1 .

21
[ 124467-36-3 ]
[ 1429914-15-7 ]

References: [1]Patent: WO2013/52394,2013,A1 .

22
[ 124467-36-3 ]
5-((1R,2S)-2-aminocyclohexylamino)-3-(5-methyl-7,8-dihydroquinolin-2-ylamino)picolinonitrile [ No CAS ]

References: [1]Patent: WO2013/52394,2013,A1 .

23
[ 124467-36-3 ]
[ 1429912-32-2 ]

References: [1]Patent: WO2013/52394,2013,A1 .

24
[ 124467-36-3 ]
[ 676-58-4 ]
[ 1429914-12-4 ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran; at 0℃;	To a solution of <strong>[124467-36-3]2-chloro-7,8-dihydroquinolin-5(6H)-one</strong> (500 mg, 2.75 mmol) in tetrahydrofuran (20 mL) at 0C was added methylmagnesium chloride (3.0 M in tetrahydrofuran, 0.92 ml, 2.8 mmol) over 2 minutes dropwise. Additional methylmagnesium chloride (3.0 M in tetrahydrofuran) were added at the following time intervals after the initial addition: 40 minutes (0.46 ml, 1.4 mmol); 60 minutes (0.46 ml, 1.4 mmol); and 120 minutes (0.92 ml, 2.8 mmol). At 1 hour after the final addition, the reaction mixture was quenched with saturated aqueous ammonium chloride solution (10 mL), and diluted with ethyl acetate (30 mL). The organic layer was separated and washed sequentially with saturated aqueous sodium bicarbonate solution and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (10-50% ethyl acetate/hexanes, linear gradient) to give 2-chloro-5-methyl-5,6,7,8-tetrahydroquinolin-5-ol. MS ESI calc'd. for C10H,3C1NO [M + H]+ 198, found 198.

References: [1]Patent: WO2013/52394,2013,A1 .Location in patent: Paragraph 00392.

25
[ 504-02-9 ]
[ 124467-36-3 ]

References: [1]Patent: US2014/31391,2014,A1 .
[2]Patent: WO2016/185342,2016,A1 .
[3]Patent: CN108218770,2018,A .

26
[ 557-21-1 ]
[ 124467-36-3 ]
[ 1471468-84-4 ]

Yield	Reaction Conditions	Operation in experiment
66%	With tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl acetamide; at 100℃; for 2h;Inert atmosphere;	Example 4A 5-Oxo-5,6,7,8-tetrahydroquinoline-2-carbonitrile Under nitrogen, 42.25 g (0.23 mol) of <strong>[124467-36-3]2-chloro-7,8-dihydroquinolin-5(6H)-one</strong>, 54.64 g (0.47 mol) of zinc cyanide and 13.44 g (0.01 mol) of tetrakis(triphenylphosphine)palladium were suspended in 200 ml of anhydrous N,N-dimethylacetamide (water content <0.01%, degassed with nitrogen beforhand), heated to 100 C. and stirred at this temperature for 2 hours. After complete conversion (monitored by TLC, mobile phase petroleum ether/ethyl acetate 2:1), the reaction mixture (grey suspension) was cooled to room temperature and filtered through Celite, and the filter cake was washed with 500 ml of ethyl acetate. 200 ml of saturated aqueous sodium chloride solution were then added to the resulting organic solution. A white precipitate was formed, which was filtered off and discarded. The organic phase was separated off, washed three times with in each case 200 ml of saturated sodium chloride solution, dried over sodium sulphate, filtered and concentrated to dryness. The residue obtained was applied to 20 g of silica gel and purified by column chromatography on silica gel (80 g cartridge; flow rate: 60 ml/min; mobile phase: petroleum ether/ethyl acetate 95:5?60:40 over 40 min, then isocratic petroleum ether/ethyl acetate 60:40 for 30 min). This gave 26.35 g (0.15 mmol, 66% of theory) of the target compound. MS (EI): m/z=172 (M)+. 1H-NMR (400 MHz, CDCl3, delta/ppm): 2.19-2.30 (m, 2H), 2.70-2.79 (m, 2H), 3.20 (t, 2H), 7.67 (d, 1H), 8.39 (d, 1H).

References: [1]Patent: US2014/31391,2014,A1 .Location in patent: Paragraph 0371; 0372; 0373; 0374.
[2]Patent: WO2017/107979,2017,A1 .Location in patent: Paragraph 1633.

27
[ 124467-36-3 ]
[ 1542132-12-6 ]