[ CAS No. 578-66-5 ] {[proInfo.proName]}

Name: 578-66-5|8-Aminoquinoline|97%
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Quality Control of [ 578-66-5 ]

COA NMR CNMR HPLC LC-MS

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Product Details of [ 578-66-5 ]

CAS No. :	578-66-5	MDL No. :	MFCD00006809
Formula :	C₉H₈N₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	WREVVZMUNPAPOV-UHFFFAOYSA-N
M.W :	144.17	Pubchem ID :	11359
Synonyms :

Calculated chemistry of [ 578-66-5 ]

Physicochemical Properties

Num. heavy atoms :	11
Num. arom. heavy atoms :	10
Fraction Csp3 :	0.0
Num. rotatable bonds :	0
Num. H-bond acceptors :	1.0
Num. H-bond donors :	1.0
Molar Refractivity :	46.15
TPSA :	38.91 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) :	-5.91 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.45
Log Po/w (XLOGP3) :	1.79
Log Po/w (WLOGP) :	1.82
Log Po/w (MLOGP) :	1.19
Log Po/w (SILICOS-IT) :	1.77
Consensus Log Po/w :	1.61

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.53
Solubility :	0.421 mg/ml ; 0.00292 mol/l
Class :	Soluble
Log S (Ali) :	-2.23
Solubility :	0.857 mg/ml ; 0.00595 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.32
Solubility :	0.0693 mg/ml ; 0.000481 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.09

Safety of [ 578-66-5 ]

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

Application In Synthesis of [ 578-66-5 ]

* 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 [ 578-66-5 ]
Downstream synthetic route of [ 578-66-5 ]

[ 578-66-5 ] Synthesis Path-Upstream 1~15

1
[ 578-66-5 ]
[ 38707-70-9 ]

Reference： [1] European Journal of Medicinal Chemistry, 2019, p. 290 - 320

2
[ 578-66-5 ]
[ 394-68-3 ]

Reference： [1] Journal of the American Chemical Society, 1949, vol. 71, p. 1785
[2] Organic Magnetic Resonance, 1982, vol. 20, # 2, p. 92 - 101

3
[ 578-66-5 ]
[ 16567-18-3 ]

Reference： [1] Journal of Organic Chemistry, 2003, vol. 68, # 13, p. 5123 - 5131
[2] European Journal of Medicinal Chemistry, 2019, p. 290 - 320

4
[ 578-66-5 ]
[ 1006-47-9 ]

Reference： [1] Organic Letters, 2014, vol. 16, # 9, p. 2306 - 2309

5
[ 578-66-5 ]
[ 10470-83-4 ]

Reference： [1] Tetrahedron Letters, 1990, vol. 31, # 34, p. 4871 - 4872
[2] Tetrahedron Letters, 1990, vol. 31, # 34, p. 4871 - 4872

6
[ 578-66-5 ]
[ 3373-00-0 ]

Reference： [1] ChemCatChem, 2018, vol. 10, # 21, p. 4980 - 4986

7
[ 578-66-5 ]
[ 53472-18-7 ]

Yield	Reaction Conditions	Operation in experiment
51%	With N-Bromosuccinimide In acetonitrile at 25℃; for 1.25 h;	4.1.16 5-Bromo-8-aminoquinoline (21) To solution of compound 12 (1.0 g, 6.94 mmol) in 46.0 mL of acetonitrile, a portion of NBS (605 mg, 3.40 mmol) was added. The reaction mixture was stirred at 25 °C for 15 min, then a second portion of NBS (667 mg, 3.75 mmol) was added. The reaction was stirred for 1 h at 25 °C. The solvent was evaporated under reduced pressure and the residue taken up with EtOAc and washed with water (3 * 50 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by flash chromatography on silica gel (10percent EtOAc in petroleum ether) to afford the title compound as an amorphous yellow solid (51percent yield). ¹H NMR (300 MHz, CDCl₃) δ 8.76 (d, 1H, J = 6.0 Hz), 8.43 (d, 1H, J = 9.0 Hz), 7.56 (d, 1H, J = 12.0), 7.48 (q, 1H, J = 3.0 Hz), 6.80 (d, 1H, J = 6.0 Hz); ESI-MS m/z 222.9 [M+H]⁺.
50%	With N-Bromosuccinimide In acetone at 20℃; for 0.5 h;	Quinolin-8-amine (0.20 g, 1.38 μMol) was dissolved in acetonitrile (20 mL), and N-bromosuccinimide (0.26 g,1.43 μMol) was added to the solution. The mixture was stirred at room temperature for 30 minutes. Water was addedto the mixture. The organic layer was extracted with ethyl acetate, dried over anhydrous sodium sulfate, and concentratedunder reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate = 90/10-> 70/30) to obtain compound 117-1 (0.15 g, 50percent).1H NMR (300 MHz, DMSO-d6, δ): 8.76 (d, J = 3.3 Hz, 1H), 8.42 (d, J = 8.1 Hz, 1H), 7.56 (d, J = 8.4 Hz, 1H), 7.48 (dd,J = 8.4, 4.2 Hz, 1H), 6.80 (d, J = 8.1 Hz, 1H), 5.04 (br, 2H).
760 mg	With N-Bromosuccinimide In acetonitrile at 20℃; for 2 h;	To a solution of 8-aminoquinoline (1 g, 4.8 mmol) in CH3CN (30 mL) were added NBS (1.28 g, 7.2 mmol). The reaction mixture was stirred at RT for 2 hour. The residue was treated with water and extracted with EA. The extracts were concentrated and the residue purifiled by silica gel chromatography to afford 5-bromo-8-quinolylamine (760 mg).

Reference： [1] European Journal of Medicinal Chemistry, 2019, p. 290 - 320
[2] Patent: EP3401309, 2018, A1, . Location in patent: Paragraph 0859
[3] Patent: WO2010/30722, 2010, A1, . Location in patent: Page/Page column 46
[4] Patent: WO2016/77240, 2016, A2, . Location in patent: Page/Page column 90; 104

8
[ 578-66-5 ]
[ 53472-18-7 ]
[ 36107-02-5 ]

Reference： [1] Chemical Science, 2018, vol. 9, # 7, p. 1782 - 1788
[2] Letters in Drug Design and Discovery, 2017, vol. 14, # 12, p. 1415 - 1424

9
[ 578-66-5 ]
[ 142340-15-6 ]

Reference： [1] Dalton Transactions, 2011, vol. 40, # 5, p. 1034 - 1037
[2] RSC Advances, 2014, vol. 4, # 37, p. 19538 - 19549
[3] Applied Organometallic Chemistry, 2010, vol. 24, # 8, p. 563 - 568
[4] Journal fuer Praktische Chemie (Leipzig), 1936, vol. <2> 145, p. 257,261
[5] Journal of Polymer Science, Part A: Polymer Chemistry, 2010, vol. 48, # 16, p. 3693 - 3701

10
[ 578-66-5 ]
[ 30465-68-0 ]

Reference： [1] Green Chemistry, 2018, vol. 20, # 11, p. 2472 - 2476

11
[ 578-66-5 ]
[ 313-16-6 ]
[ 483-69-2 ]

Yield	Reaction Conditions	Operation in experiment
59%	at 20℃; for 1 h; Irradiation; Inert atmosphere	General procedure: 1,3,5-Trimethoxybenzene (1a; 50.5 mg, 0.3 mmol) and Umemoto reagentII (6; 43.8 mg, 0.1 mmol) were charged into a reaction tube (borosilicateglass JR-1, thickness = 1.8 mm), which was flame-dried undervacuum. The tube was evacuated and back-filled with argon.DMSO (1 mL) was then added to the tube. The mixture was stirred for1 h under photo-irradiation (375 nm, 3-W LED × 1, 1.5 cm away fromthe tube) at r.t. The solution was diluted with EtOAc, and the resulting organic layer was washed with sat. aq NaHCO3. After extraction withEtOAc, the combined organic layers were dried (Na2SO4). After filtration,the filtrate was concentrated in vacuo and the residue was submitted to 19F NMR analysis to determine the NMR yield with α,α,α-trifluorotoluene as an internal standard. After evaporation of CDCl3,the residue was purified by column chromatography (silica gel, nhexane/EtOAc 9:1) to provide 2a (21.8 mg, 92percent) as a colorless solid

Reference： [1] Synthesis (Germany), 2018, vol. 50, # 15, p. 2948 - 2953

12
[ 887144-94-7 ]
[ 578-66-5 ]
[ 313-16-6 ]
[ 483-69-2 ]

Reference： [1] Organic and Biomolecular Chemistry, 2016, vol. 14, # 34, p. 8092 - 8100

13
[ 578-66-5 ]
[ 2314-97-8 ]
[ 313-16-6 ]
[ 483-69-2 ]
[ 1027791-33-8 ]

Reference： [1] Journal of Fluorine Chemistry, 2010, vol. 131, # 1, p. 98 - 105

14
[ 578-66-5 ]
[ 483-69-2 ]

Reference： [1] Organic and Biomolecular Chemistry, 2016, vol. 14, # 34, p. 8092 - 8100

15
[ 578-66-5 ]
[ 2314-97-8 ]
[ 313-16-6 ]
[ 483-69-2 ]

Reference： [1] Journal of Heterocyclic Chemistry, 1994, vol. 31, # 6, p. 1413 - 1416

[ 578-66-5 ] Synthesis Path-Downstream 1~88

1
[ 578-66-5 ]
[ 394-68-3 ]

Reference： [1]Journal of the American Chemical Society,1949,vol. 71,p. 1785
[2]Organic Magnetic Resonance,1982,vol. 20,p. 92 - 101

2
[ 611-33-6 ]
[ 578-66-5 ]

Reference： [1]Chemistry - A European Journal,2010,vol. 16,p. 1983 - 1991
[2]Chemistry - A European Journal,2013,vol. 19,p. 2131 - 2141
[3]Zhurnal Obshchei Khimii,1936,vol. 6,p. 681,682
Chemisches Zentralblatt,1936,vol. 107,p. 2912

3
[ 578-66-5 ]
[ 35999-20-3 ]
[ 97802-10-3 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions II,1985,p. 705 - 710

4
[ 578-66-5 ]
[ 14562-10-8 ]
N-8-quinolinyl 3-phenyl-2-hydroxybenzylimine [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2005,vol. 127,p. 11037 - 11046

5
[ 578-66-5 ]
[ 210532-25-5 ]
[ 893779-53-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2007,vol. 15,p. 7553 - 7560

6
[ 578-66-5 ]
methyl-<β-chloro-ethyl>-amine hydrochloride [ No CAS ]
[ 86-58-8 ]

Reference： [1]Journal of Organic Chemistry,2003,vol. 68,p. 5123 - 5131

7
[ 148-24-3 ]
Cs₂ CO₃ [ No CAS ]
[ 7462-74-0 ]
[ 578-66-5 ]

Yield	Reaction Conditions	Operation in experiment
	With 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; NaH; In 1,4-dioxane;	Preparation of 8-aminoquinoline To a solution of 8-hydroxyquinoline (537 mg, 3.70 mmol) in dioxane (20 mL) was added NaH (Aldrich, dry, 300 mg, 12.2 mmol) and Cs2 CO3 (4.00 g, 12.2 mmol). The resulting mixture was stirred at room temperature for about 30 minutes, then 2-bromo-2-methyl-propanamide (2.03 g, 12.2 mmol) was added and the resulting mixture was stirred at reflux for 16 h. After the reflux period, NMP (20 mL), DMPU (2 mL), and NaH (Aldrich, dry, 100 mg, 4.07 mmol) were added. The resulting mixture was stirred at 150 C. for 72 h. The reaction was cooled to room temp., and partitioned between water (50 mL) and EtOAc (100 mL). The aqueous layer was extracted with EtOAc (100 mL) and the combined organics washed with water (2*50 mL), dried (Na2 SO4), and concentrated to about 3 g of material. The brown oil was chromatographed on silica (200 mL, 4 cm diam. column), eluding with 30:70:1 EtOAc/hexane/NEt3 to obtain 8-aminoquinoline as an off-white solid (220 mg, 1.53 mmol, 41.3% yield).: mp 65-67 C. (lit. 62.5-64 C., Dewar, M. J. S. et. al., Journal of the Chemical Society, 1956, 2556 and 62.5-64 C., Richardson, A. et. al., Journal of Organic Chemistry, 1960, 25, 1138); 1 H NMR (300 MHz, CDCl3) delta8.76 (dd, 1 H, J=4.23, 1.75 Hz), 8.06 (dd, 1 H, J=8.20, 1.96), 7.37-7.30 (om's, 2 H), 7.15 (dd, 1 H, J=8.01, 1.30), 6.92 (dd, 1 H, J=7.51, 1.42), 4.98 (br s, 2 H, N--H2); MS (EI) 144; Analysis: Calculated C 74.98, H 5.59, N 19.43; Found C 74.88, H 5.67, N 19.26.

Reference： [1]Patent: US6034241,2000,A

8
[ 578-66-5 ]
[ 102308-97-4 ]
1'-carbonyl diimidazole [ No CAS ]
N-(1-Methyl-5-indolyl)-N'-(6-quinolyl)-urea hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
31%		Example 11 N-(1-Methyl-5-indolyl)-N'-(8-quinolyl) urea (E11) The title compound was prepared from 8-aminoquinoline, 1, 1'-carbonyl diimidazole and 5-amino-1-methyl-indole (D2) using a procedure similar to that described for Example 10, in 31% yield, m.p. 205-209 C. NMR (D6 -DMSO) delta: 3.76 (3H, s), 6.35 (1H, d, J 3), 7.22 (1H, dd, J 6, 2), 7.27 (1H, d, J 3), 7.36 (1H, d, J 6), 7.5-7.54 (2H, m), 7.60-7.65 (1H, m), 7.8 (1H, s), 8.39 (1H, d, J 6), 8.57 (1H, m), 8.92 (1H, d, J 2), 9.62 (2H, s). Found: M+ 316 C19 H16 N4 O requires 316

Reference： [1]Patent: US5508288,1996,A

9
[ 872-50-4 ]
[ 148-24-3 ]
[ 7462-74-0 ]
[ 578-66-5 ]

Yield	Reaction Conditions	Operation in experiment
	With 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; NaH; caesium carbonate; In 1,4-dioxane;	Preparation of 8-aminoquinoline. To a solution of 8-hydroxyquinoline (537 mg, 3.70 mmol) in dioxane (20 mL) was added NaH (Aldrich, dry, 300 mg, 12.2 mmol) and Cs2CO3 (4.00 g, 12.2 mmol). The resulting mixture was stirred at room temperature for about 30 minutes, then 2-bromo-2-methyl-propanamide (2.03 g, 12.2 mmol) was added and the resulting mixture was stirred at reflux for 16 h. After the reflux period, NMP (20 mL), DMPU (2 mL), and NaH (Aldrich, dry, 100 mg, 4.07 mmol) were added. The resulting mixture was stirred at 150 C for 72 h. The reaction was cooled to room temp., and partitioned between water (50 mL) and EtOAc (100 mL). The aqueous layer was extracted with EtOAc (100 mL) and the combined organics washed with water (2 x 50 mL), dried (Na2SO4), and concentrated to about 3 g of material. The brown oil was chromatographed on silica (200 mL, 4 cm diam. column), eluding with 30:70:1 EtOAc/hexane/NEt3 to obtain 8-aminoquinoline as an off-white solid (220 mg, 1.53 mmol, 41.3% yield).: mp 65-67C (lit. 62.5-64 C, Dewar, M.J.S. et. al., Journal of the Chemical Society, 1956, 2556 and 62.5-64 C, Richardson, A. et. al., Journal of Organic Chemistry,1960, 25, 1138); 1H NMR (300 MHz, CDCl3) delta 8.76 (dd, 1 H, J = 4.23, 1.75 Hz), 8.06 (dd, 1 H, J = 8.20, 1.96), 7.37-7.30 (om's, 2 H), 7.15 (dd, 1 H, J = 8.01, 1.30), 6.92 (dd, 1 H, J = 7.51, 1.42), 4.98 (br s, 2 H, N-H2); MS (EI) 144; Analysis: Calculated C 74.98 H 5.59 N 19.43 Found C 74.88 H 5.67 N 19.26.

Reference： [1]Patent: EP944600,2002,B1

10
[ 578-66-5 ]
[ 86-59-9 ]
[ 924895-86-3 ]

Yield	Reaction Conditions	Operation in experiment
96%		N-8-quinolinyl-8-quinoline carboxamide (compound 24) (Benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (192 mg; 0.43 mmol), 1-hydroxybenzotriazole monohydrate (79 mg; 0.59 mmol) and triethylamine (0.200 ml; 1.44 mmol) are added to a solution of quinoline-8-carboxylic acid (50 mg; 0.29 mmol) dissolved in 5 ml of dry CH2Cl2. After stirring for 30 minutes at ambient temperature, 8-aminoquinoline (84 mg; 0.58 mmol) is added and the mixture is stirred for 4 hours 30 minutes at ambient temperature. Water (10 ml) is added and the product is extracted with CH2Cl2 (3*10 ml). The volume is reduced and the product is purified by silica gel chromatography, eluted with CH2Cl2/CH3OH (0 to 2percent, v/v) then the solvent is evaporated under reduced pressure and the fractions containing a high proportion of products are repurified by silica gel chromatography, eluted with CH2Cl2/CH3OH (99.5/0.5; v/v). 24 is obtained after evaporation of the solvent in the form of a white powder (83 mg; 0.28 mmol, yield=96percent). NMR-1H (250 MHz, CDCl3) delta, ppm: 15.13 (s, 1H); 9.25 (dd, 3J (H, H)=4.0 Hz, 4J (H, H)=2.0 Hz, 1H); 9.19 (dd, 3J (H, H)=7.5 Hz, 4J (H, H)=1.5 Hz, 1H); 9.00 (m, 2H); 8.32 (dd, 3J (H, H)=8.0 Hz, 4J (H, H)=2.0 Hz, 1H); 8.19 (dd, 3J (H, H)=8.0 Hz, 4J (H, H)=1.5 Hz, 1H); 8.01 (dd, 3J (H, H)=8.0 Hz, 4J (H, H)=1.5 Hz, 1H); 7.74 (dd, 3J (H, H)=7.5 and 8.0 Hz, 1H); 7.60 (m, 3H); 7.48 (dd, 3J (H, H)=4.5 and 8.0 Hz, 1H). NMR-13C (63 MHz, CDCl3) delta, ppm:; 164.28; 149.48; 148.57; 145.60; 140.12; 137.59; 136.65; 136.18; 134.02; 132.10; 129.85; 128.41; 128.28; 127.50; 126.63; 121.75; 121.34; 121.12; 118.18. MS (CID, NH3): m/z=300 (MH+). UV/vis [DMSO/20 mM Tris-HCl pH=7.4 containing 150 mM NaCl (8/2, v/v)]: lambda nm (epsilon M-1 cm-1)=261 (13,300, shoulder), 274 (14,800), 294 (12,200).

Reference： [1]Patent: US2009/227626,2009,A1 .Location in patent: Page/Page column 31

11
[ 6940-57-4 ]
[ 578-66-5 ]
[ 1132769-80-2 ]

Yield	Reaction Conditions	Operation in experiment
17%	In methanol; for 96h;Reflux;	Example 4; Condensation of 1.95 g of 6-methyl-2-acetylpyridine (14.4 mmol) and of 2.08 g of 8-aminoquinoleine (14.4 mmol) with 0.4 mL formic acid HCOOH is carried out in 30 mL anhydrous MeOH. The reaction medium is stirred under reflux for 96 h. After evaporation of the methanol under vacuum, the raw product is purified on a silica column (eluent: CH2Cl2/ethyl acetate 95/5). 0.8 g of a bright yellow solid is obtained (yield: 17%).1H NMR: deltaH (300 MHz, CD2Cl2) 1.87 (s, 3H), 2.54 (s, 3H), 2.59 (s, 3H), 6.12 (d, 1H, J 2.3 Hz), 6.93 (d, H, J 8.7 Hz), 6.94 (s, 1H), 6.97 (dt, 1H, J 7.5 and 0.75 Hz), 7.15 (dm, 1H, J 7.7 Hz), 7.27 (dm, 1H, J 7.3 Hz), 7.29-7.38 (m, 3H), 7.50 (t, 1H, J 7.7 Hz), 7.64 (t, 1H, J 7.7 Hz), 8.01 (dd, 1H, J 8.2 and 1.7 Hz), 8.75 (dd, 1H, J 4.2 and 1.8 Hz) ppm;13C NMR: deltaC (75 MHz, CD2Cl2) 24.69, 24.72, 31.1, 59.1, 113.7, 115.6, 117.1, 120.9, 121.4, 121.7, 122.1, 125.3, 128.9, 129.9, 136.1, 136.3, 137.1, 137.7, 140.6, 147.9, 157.7, 158.36, 158.49, 165.9 ppm;IR: 3373, 3055, 2965, 2920, 1733, 1637, 1586, 1572, 1511, 1478, 1456, 1384, 1256, 1225, 1167, 1124, 1099, 1063, 996, 856, 818, 806, 798, 752, 703 cm-1.MS: El m/z 363, 286, 270, 256, 243, 189, 181.The structural formula of the product A obtained is as follows:

Reference： [1]Dalton Transactions,2009,p. 770 - 772
[2]Patent: US2011/9635,2011,A1 .Location in patent: Page/Page column 4

12
[ 59576-26-0 ]
[ 578-66-5 ]
[ 1132769-81-3 ]

Reference： [1]Dalton Transactions,2009,p. 770 - 772

13
[ 578-66-5 ]
[ 53472-18-7 ]

Yield	Reaction Conditions	Operation in experiment
56%	With tetrabutylammomium bromide; copper(ll) bromide; In ethanol; at 25℃;	General procedure: A round bottom flask was charged with Bu4NBr (2 mmol, 0.64 g), EtOH (8 mL) and 2-methylaniline (2 mmol, 0.21 g) followed by CuBr2 (3 mmol, 0.67 g). The resulted mixture was stirred at 25 C. After the completion of the reaction (monitored by TLC), the solvent was evaporated under reduced pressure. To the residue was added ammonium hydroxide (5 mL, 25% w/v) and water (5 mL) with stirring, and the suspension was extracted with DCM(10 mL×4) The organic phase was washed with saturated brine and dried over anhydrous Na2SO4. The product 2b was obtained using flash chromatograph column eluted with PE : EA (5 : 1).
51%	With N-Bromosuccinimide; In acetonitrile; at 25℃; for 1.25h;	4.1.16 5-Bromo-8-aminoquinoline (21) To solution of compound 12 (1.0?g, 6.94?mmol) in 46.0?mL of acetonitrile, a portion of NBS (605?mg, 3.40?mmol) was added. The reaction mixture was stirred at 25?C for 15?min, then a second portion of NBS (667?mg, 3.75?mmol) was added. The reaction was stirred for 1?h?at 25?C. The solvent was evaporated under reduced pressure and the residue taken up with EtOAc and washed with water (3?*?50?mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by flash chromatography on silica gel (10% EtOAc in petroleum ether) to afford the title compound as an amorphous yellow solid (51% yield). 1H NMR (300?MHz, CDCl3) delta 8.76 (d, 1H, J?=?6.0?Hz), 8.43 (d, 1H, J?=?9.0?Hz), 7.56 (d, 1H, J?=?12.0), 7.48 (q, 1H, J?=?3.0?Hz), 6.80 (d, 1H, J?=?6.0?Hz); ESI-MS m/z 222.9 [M+H]+.
50%	With N-Bromosuccinimide; In acetone; at 20℃; for 0.5h;	Quinolin-8-amine (0.20 g, 1.38 muMol) was dissolved in acetonitrile (20 mL), and N-bromosuccinimide (0.26 g,1.43 muMol) was added to the solution. The mixture was stirred at room temperature for 30 minutes. Water was addedto the mixture. The organic layer was extracted with ethyl acetate, dried over anhydrous sodium sulfate, and concentratedunder reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate = 90/10-> 70/30) to obtain compound 117-1 (0.15 g, 50%).1H NMR (300 MHz, DMSO-d6, delta): 8.76 (d, J = 3.3 Hz, 1H), 8.42 (d, J = 8.1 Hz, 1H), 7.56 (d, J = 8.4 Hz, 1H), 7.48 (dd,J = 8.4, 4.2 Hz, 1H), 6.80 (d, J = 8.1 Hz, 1H), 5.04 (br, 2H).

	With N-Bromosuccinimide; In acetonitrile; for 0.75h;	INTERMEDIATE 7 5-BROMO-7-CHLOROQUINOLINEStep A. 8-Amino-5-bromoquinolineTo a solution of 8-aminoquinoline (4.0 g, 28 mmol) in CH3CN (185 mL) was added N-bromosuccinimide (2,47 g, 13.9 mmol). After stirring for 15 minutes, a second portion10 of N-bromosuccinimide (2.71 g, 15.2 mmol) was added. After stirring for an additional 30 minutes, the mixture was concentrated. The residue was dissolved in EtOAc, then washed with water (2 x 100 mL) and saturated NaCl (aq) (100 mL). The organics were dried over Na2SO4, filtered, then concentrated. The residue was purified by silica gel chromatography eluting with 10- 15% EtOAc/hexanes to afford the title compound as a white solid: 1H NMR (500 MHz,15 CDCl3): delta 8.79 (dd, J = 1.5, 4.1 Hz, IH), 8.46 (dd, J - 1.5, 8.5 Hz, IH), 7.60 (d, J = 8.1 Hz, IH), 7.52 (dd, J = 4.1, 8.5 Hz, IH), 6.83 (d, J = 8.1 Hz, IH); LC7: 2.48 min. (M+H) 225.
760 mg	With N-Bromosuccinimide; In acetonitrile; at 20℃; for 2h;	To a solution of 8-aminoquinoline (1 g, 4.8 mmol) in CH3CN (30 mL) were added NBS (1.28 g, 7.2 mmol). The reaction mixture was stirred at RT for 2 hour. The residue was treated with water and extracted with EA. The extracts were concentrated and the residue purifiled by silica gel chromatography to afford 5-bromo-8-quinolylamine (760 mg).

Reference： [1]Synthetic Communications,2019,vol. 49,p. 1406 - 1415
[2]European Journal of Medicinal Chemistry,2019,vol. 162,p. 290 - 320
[3]Patent: EP3401309,2018,A1 .Location in patent: Paragraph 0859
[4]Molecules,2019,vol. 24
[5]Patent: WO2010/30722,2010,A1 .Location in patent: Page/Page column 46
[6]Patent: WO2016/77240,2016,A2 .Location in patent: Page/Page column 90; 104

14
[ 188417-26-7 ]
[ 578-66-5 ]
[ 1223077-75-5 ]

Reference： [1]Russian Journal of General Chemistry,2009,vol. 79,p. 2402 - 2405

15
[ 578-66-5 ]
[ 35432-36-1 ]
[ 1232007-60-1 ]

Reference： [1]Journal of the American Chemical Society,2010,vol. 132,p. 8232 - 8233

16
[ 578-66-5 ]
[ 60230-36-6 ]
[ 1177862-02-0 ]

Reference： [1]Journal of the American Chemical Society,2010,vol. 132,p. 8232 - 8233

17
[ 578-66-5 ]
[ 63624-28-2 ]
[ 1232007-56-5 ]

Reference： [1]Journal of the American Chemical Society,2010,vol. 132,p. 8232 - 8233

18
[ 578-66-5 ]
[ 34420-17-2 ]
[ 329371-10-0 ]

Reference： [1]Synlett,2010,p. 2101 - 2105

19
[ 578-66-5 ]
[ 83-40-9 ]
[ 1019445-29-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 6653 - 6656

20
[ 578-66-5 ]
[ 104612-36-4 ]
[ 1257883-60-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 6653 - 6656

21
[ 578-66-5 ]
[ 4025-75-6 ]
[ 1271760-35-0 ]

Reference： [1]Chemistry - An Asian Journal,2011,vol. 6,p. 410 - 414

22
[ 578-66-5 ]
[ 10130-87-7 ]
[ 1280821-35-3 ]

Reference： [1]Journal of Medicinal Chemistry,2019,vol. 62,p. 1609 - 1625

23
[ 578-66-5 ]
[ 42918-86-5 ]
[ 1449300-02-0 ]

Reference： [1]Journal of the American Chemical Society,2013,vol. 135,p. 12135 - 12141

24
[ 578-66-5 ]
[ 74346-19-3 ]
[ 1609401-43-5 ]

Yield	Reaction Conditions	Operation in experiment
92%		General procedure: A solution of 8-aminoquinoline (0.3950 g, 2.74 mmol) and Et3N (0.42 mL, 3 mmol) in CH2Cl2 (5 mL) was cooled to 0 C, then an acyl chloride (2.74 mmol) was added (the acyl chloride was prepared by reaction of the appropriate carboxylic acid with SOCl2). After addition, the reaction mixture was warmed to room temperature and stirred for 24 h. The reaction mixture was washed with water (1 mL), brine (1.5 mL × 3), and dried over Na2SO4. The solvent was removed and theproduct was obtained by recrystallisation or flash chromatography.

Reference： [1]Journal of Chemical Research,2013,vol. 37,p. 606 - 610

25
[ 578-66-5 ]
[ 74346-19-3 ]
[ 1609401-47-9 ]

Reference： [1]Journal of Chemical Research,2013,vol. 37,p. 606 - 610

26
[ 578-66-5 ]
[ 89694-46-2 ]
[ 1644565-60-5 ]

Reference： [1]Chemistry - A European Journal,2014,vol. 20,p. 8761 - 8770

27
[ 611-08-5 ]
[ 578-66-5 ]
manganese(II) chloride tetrahydrate [ No CAS ]
C₁₃H₁₀MnN₅O₄⁽¹⁺⁾ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39%		General procedure: A solution of 8AQ (1 mmol) dissolved in 70C methanol(30 mL) was added a solution of metal salts (1 mmol in 2mL methanol), and then heated for 45 min. Subsequently, asolution of 5Iu or 5Nu (1 mmol in 2 mL methanol) wasadded to the reaction mixture and heated for another 1 h.The formed solid product was collected by filtration, washed3-4 times with cold MeOH and dried under reduced preesureat room temperature

Reference： [1]Letters in drug design and discovery,2013,vol. 10,p. 859 - 864

28
[ 611-08-5 ]
[ 578-66-5 ]
[ 6046-93-1 ]
C₁₃H₁₀CuN₅O₄⁽¹⁺⁾ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94.9%		General procedure: A solution of 8AQ (1 mmol) dissolved in 70C methanol(30 mL) was added a solution of metal salts (1 mmol in 2mL methanol), and then heated for 45 min. Subsequently, asolution of 5Iu or 5Nu (1 mmol in 2 mL methanol) wasadded to the reaction mixture and heated for another 1 h.The formed solid product was collected by filtration, washed3-4 times with cold MeOH and dried under reduced preesureat room temperature

Reference： [1]Letters in drug design and discovery,2013,vol. 10,p. 859 - 864

29
[ 611-08-5 ]
[ 578-66-5 ]
[ 6046-93-1 ]
C₁₃H₁₀N₅NiO₄⁽¹⁺⁾ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68.2%		General procedure: A solution of 8AQ (1 mmol) dissolved in 70C methanol(30 mL) was added a solution of metal salts (1 mmol in 2mL methanol), and then heated for 45 min. Subsequently, asolution of 5Iu or 5Nu (1 mmol in 2 mL methanol) wasadded to the reaction mixture and heated for another 1 h.The formed solid product was collected by filtration, washed3-4 times with cold MeOH and dried under reduced preesureat room temperature

Reference： [1]Letters in drug design and discovery,2013,vol. 10,p. 859 - 864

30
[ 4994-86-9 ]
[ 578-66-5 ]
N-(2-methylpyrimidin-4-yl)quinolin-8-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45%		General procedure: To a well stirred 8-aminoquinoline (1 mmol) indry DMF (5 mL), sodium hydride (1.2 mmol, 60% in mineral oil) was added at 0 C.After 10 min stirring, the corresponding heterocyclic chloro compound (1.2mmol) was added and stirred for 10 min at rt then heated at 60 C for 5-12 h.Upon completion, the reaction mixture was poured into crushed ice and theresulting solid was filtered, washed with water and dried under vacuum. Thesolid was triturated with methanol and dried under vacuum to afford targetcompound as a solid.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 1100 - 1103

31
[ 86-58-8 ]
[ 578-66-5 ]

Yield	Reaction Conditions	Operation in experiment
95%	With sodium hydroxide; hydroxylamine-O-sulfonic acid; In water; acetonitrile; for 1.5h;Sonication;	General procedure: Reactions facilitated by sonication were performed on a 1.0 mmol scale. Arylboronic acid 3 (1.0 equiv) and MeCN (5.0 mL) were added to a 25 mL microwave vial equipped with a stir bar, followed by HSA (1.5 equiv) and aq 1 M NaOH (5 equiv). The mixture was capped and set to stir for 5 min, then placed in an ultrasonic cleaner for 30 min (35 kHz, 90 W), at which time the vial was removed and a small aliquot was taken for reaction monitoring via HPLC analysis. The mixture was then placed back in the sonication bath for 30 min. This process was repeated until the reaction had gone to completion, or the reaction failed to progress, as monitored by HPLC. The reaction mixture was diluted with H2O (30 mL) and extracted with EtOAc (2 × 30mL). The combined organic extracts were dried (Na2SO4) and concentrated in vacuo. The residue was purified by flash chromatography (EtOAc/hexanes) to afford the desired amine product 2.

Reference： [1]Synthesis,2017,vol. 49,p. 2555 - 2561
[2]Journal of Organic Chemistry,2015,vol. 80,p. 2545 - 2553

32
[ 578-66-5 ]
[ 164365-88-2 ]
tert-butyl (4-(quinolin-8-yl-amino)butyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
17%	With caesium carbonate; In N,N-dimethyl-formamide; at 120℃; for 0.666667h;Sealed tube; Microwave irradiation;	A microwave vessel, equipped with a magnetic stir bar and a septum, was charged with a mixture of cesium carbonate (3.26 g, 10 mmol), 8-aminoquinoline (0.59 g, 5.2 mmol), and 6a (1.31 g, 5.2 mmol) in DMF (4 mL). The vessel was sealed and irradiated at 120 C for 40 mm. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate, and the organic layer was washed with 10% aqueous lithium chloride. The organic fraction was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude was purified by silica gel flash chromatography, eluting with hexanes/diethyl ether, from 95/5 to 7/3, affording 0.28 g (0.9 mmol, 17% yield) of pure, target product, as a colorless oil. ?H NMR (400 MHz, CDC13): = 8.71 (dd, 1 H); 8.06 (dd, 1 H); 7.4 1-7.36 (m, 2 H); 7.05 (d, 1 H); 6.67 (d, 1 H); 6.14 (bs, 1 H); 4.57 (bs, 1 H); 3.38-3.34 (m, 2 H); 3.22-3.20 (m, 2 H); 1.86-1.79 (m, 2 H); 1.73-1.66 (m, 2 H); 1.46 (s, 9 H).

Reference： [1]ACS Medicinal Chemistry Letters,2015,vol. 6,p. 1156 - 1161
[2]Patent: WO2017/53360,2017,A1 .Location in patent: Paragraph 0159; 0160

33
[ 578-66-5 ]
[ 83948-54-3 ]
tert-butyl (5-(quinolin-8-yl-amino)pentyl)carbamate [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2015,vol. 6,p. 1156 - 1161

34
[ 578-66-5 ]
[ 6540-33-6 ]
2-cyclobutyl-N-(quinolin-8-yl)acetamide [ No CAS ]

Reference： [1]Organic Letters,2016,vol. 18,p. 48 - 51

35
[ 578-66-5 ]
[ 28697-07-6 ]
(±)-benzyl 2-(quinolin-8-ylcarbamoyl)piperidine-1-carboxylate [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2019,vol. 17,p. 4342 - 4349
[2]European Journal of Organic Chemistry,2016,vol. 2016,p. 139 - 149

36
[ 578-66-5 ]
[ 72135-36-5 ]
4-bromo-2-methoxy-N-(quinolin-8-yl)benzamide [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2016,vol. 81,p. 831 - 841

37
[ 578-66-5 ]
[ 72135-36-5 ]
4-bromo-2-hydroxy-N-(quinolin-8-yl)benzamide [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2016,vol. 81,p. 831 - 841

38
[ 578-66-5 ]
[ 18294-87-6 ]
2-cyclohexenyl-N-(quinolin-8-yl)acetamide [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2016,vol. 81,p. 956 - 968

39
[ 578-66-5 ]
[ 6324-10-3 ]
4,5-dibromo-N-(quinolin-8-yl)thiophene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		[00455] 4,5-Dibromothiophene-2-carboxylic acid (1.0 mmol) and N-(3- dimethylaminopropyl)-N?-ethylcarbodiimide hydrochloride (1.2 mmol) were dissolved in dimethylformamide (5 mL). N,N-Diisopropylethylamine (1.5 mmol) was added and the solution was stirred for 10 mm. To this solution 8-aminoquinoline (1.0 mmol) was added, and the mixture was stirred for 20 hrs. The mixture was diluted with water and extracted with 2 volumes of ethyl acetate. The organic layers were collected and the solvent was removed by rotary evaporation. The residue was purified by preparative reverse-phase HPLC using a wateracetonitrile gradient to afford the desired product Hi. ESI-MS: m/z 413 [M+H].
		4,5-Dibromothiophene-2-carboxylic acid (1.0 mmol) and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (1.2 mmol) were dissolved in dimethylformamide (5 mL). N,N-Diisopropylethylamine (1.5 mmol) was added and the solution was stirred for 10 min. To this solution 8-aminoquinoline (1.0 mmol) was added, and the mixture was stirred for 20 hrs. The mixture was diluted with water and extracted with 2 volumes of ethyl acetate. The organic layers were collected and the solvent was removed by rotary evaporation. The residue was purified by preparative reverse-phase HPLC using a water-acetonitrile gradient to afford the desired product H11. ESI-MS: m/z 413 [M+H]+.

Reference： [1]Patent: WO2016/32569,2016,A1 .Location in patent: Page/Page column 215
[2]Patent: US2019/151303,2019,A1 .Location in patent: Paragraph 0718

40
[ 578-66-5 ]
[ 16694-18-1 ]
4-bromo-N-(quinolin-8-yl)thiophene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		[00451] Benzofuran-2-carboxylic acid (1.0 mmol) and N-(3-dimethylaminopropyl)-N?- ethylcarbodiimide hydrochloride (1.2 mmol) were dissolved in dimethylformamide (5 mL). N,N-Diisopropylethylamine (1.5 mmol) was added and the solution was stirred for 10 mm. To this solution 8-aminoquinoline (1.0 mmol) was added, and the mixture was stirred for 20 hrs. The mixture was diluted with water and extracted with 2 volumes of ethyl acetate. The organic layers were collected and the solvent was removed by rotary evaporation. The residue was purified by preparative reverse-phase HPLC using a water-acetonitrile gradient to afford the desired product H7. ESI-MS: m/z 289 [M+H]b.
		4-Bromo-2-thiophenecarboxylic acid (1.0 mmol) and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (1.2 mmol) were dissolved in dimethylformamide (5 mL). N,N-Diisopropylethylamine (1.5 mmol) was added and the solution was stirred for 10 min. To this solution 8-aminoquinoline (1.0 mmol) was added, and the mixture was stirred for 20 hrs. The mixture was diluted with water and extracted with 2 volumes of ethyl acetate. The organic layers were collected and the solvent was removed by rotary evaporation. The residue was purified by preparative reverse-phase HPLC using a water-acetonitrile gradient to afford the desired product H9. ESI-MS: m/z 334 [M+H]+.

Reference： [1]Patent: WO2016/32569,2016,A1 .Location in patent: Page/Page column 214; 215
[2]Patent: US2019/151303,2019,A1 .Location in patent: Paragraph 0716

41
[ 40915-37-5 ]
[ 578-66-5 ]
[ 1428858-71-2 ]

Reference： [1]Chemistry - An Asian Journal,2016,vol. 11,p. 380 - 384

42
[ 40915-37-5 ]
[ 578-66-5 ]
7,8-dipropyl-1-(quinolin-8-yl)-4,5-dihydro-2H-pyrano[3,2-c]pyridin-2(1H)-one [ No CAS ]

Reference： [1]Chemistry - An Asian Journal,2016,vol. 11,p. 380 - 384

43
[ 578-66-5 ]
[ 10276-09-2 ]
2,2-dimethyl-N-(quinolin-8-yl)but-3-enamide [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2016,vol. 138,p. 5805 - 5808
[2]Chemical Communications,2019,vol. 55,p. 10523 - 10526

44
[ 578-66-5 ]
[ 10276-09-2 ]
4-(2,5-dioxopyrrolidin-1-yl)-2,2-dimethyl-N-(quinolin-8-yl)butanamide [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2016,vol. 138,p. 5805 - 5808

45
[ 578-66-5 ]
[ 25177-85-9 ]
N-(quinolin-8-yl)-2,3-dihydroindene-2-carboxamide [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2016,vol. 14,p. 5728 - 5743

46
[ 578-66-5 ]
[ 16650-55-8 ]
4-bromo-1-(quinolin-8-yl)-1-naphthamide [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2016,vol. 81,p. 9647 - 9657

47
[ 578-66-5 ]
[ 1460-16-8 ]
C₂₀H₂₈N₂OSi [ No CAS ]

Reference： [1]Chemical Communications,2016,vol. 52,p. 13151 - 13154

48
[ 578-66-5 ]
[ 1460-16-8 ]
[ 1385719-16-3 ]

Reference： [1]Chemical Communications,2016,vol. 52,p. 13151 - 13154

49
[ 578-66-5 ]
[ 28697-07-6 ]
C₂₄H₂₄N₂O₃ [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2016,vol. 81,p. 11646 - 11655

50
[ 578-66-5 ]
[ 5669-14-7 ]
2-benzyl-2-methyl-3-morpholino-N-(quinolin-8-yl)propanamide [ No CAS ]

Reference： [1]Chemistry - A European Journal,2016,vol. 22,p. 16057 - 16061

51
[ 578-66-5 ]
[ 5669-14-7 ]
[ 1328064-88-5 ]

Reference： [1]Chemistry - A European Journal,2016,vol. 22,p. 16057 - 16061

52
[ 578-66-5 ]
[ 2498-50-2 ]
(E)-4-((8-aminoquinolin-7-yl)diazenyl)benzimidamide [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2017,vol. 8,p. 492 - 497

53
[ 578-66-5 ]
[ 51077-14-6 ]
(S)-tert-butyl 2-(quinolin-8-ylcarbamoyl)azetidine-1-carboxylate [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2017,vol. 139,p. 11300 - 11306

54
[ 578-66-5 ]
[ 32857-63-9 ]
C₂₁H₂₂N₂O [ No CAS ]

Reference： [1]Organic Letters,2017,vol. 19,p. 5106 - 5109
[2]European Journal of Organic Chemistry,2018,vol. 2018,p. 6167 - 6175
[3]Journal of Organic Chemistry,2019,vol. 84,p. 13194 - 13202

55
[ 578-66-5 ]
[ 39891-13-9 ]
C₁₆H₁₂ClN₃O [ No CAS ]

Reference： [1]Organic Letters,2017,vol. 19,p. 5106 - 5109
[2]Journal of Organic Chemistry,2019,vol. 84,p. 13194 - 13202

56
[ 578-66-5 ]
[ 13612-34-5 ]
2-(2,5-dimethylphenyl)-N-(quinolin-8-yl)acetamide [ No CAS ]

Reference： [1]Chemistry - A European Journal,2017,vol. 23,p. 17659 - 17662

57
[ 578-66-5 ]
[ 13612-34-5 ]
(E)-methyl 3-(3,6-dimethyl-2-(2-oxo-2-(quinolin-8-ylamino)ethyl)phenyl)acrylate [ No CAS ]

Reference： [1]Chemistry - A European Journal,2017,vol. 23,p. 17659 - 17662

58
[ 578-66-5 ]
[ 10242-02-1 ]
C₁₉H₁₅N₃O [ No CAS ]