391-78-6|6-Fluoro-4-hydroxyquinoline| Ambeed

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Quality Control of [ 391-78-6 ] Purity: 98% SDS Specification

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Product Details of [ 391-78-6 ]

CAS No. :	391-78-6
Formula :	C₉H₆FNO
M.W :	163.15
SMILES Code :	OC1=CC=NC2=C1C=C(F)C=C2
MDL No. :	MFCD00269610
InChI Key :	BYZXOYSEYWCLOK-UHFFFAOYSA-N
Pubchem ID :	2774498

Safety of [ 391-78-6 ]

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

Computational Chemistry of [ 391-78-6 ] Show Less

Physicochemical Properties

Num. heavy atoms	12
Num. arom. heavy atoms	10
Fraction Csp3	0.0
Num. rotatable bonds	0
Num. H-bond acceptors	3.0
Num. H-bond donors	1.0
Molar Refractivity	43.72
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	33.12 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.47
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	0.68
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.5
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.	1.61
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	2.38
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.73

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.9
Solubility	2.07 mg/ml ; 0.0127 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-0.95
Solubility	18.2 mg/ml ; 0.112 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-3.4
Solubility	0.0657 mg/ml ; 0.000403 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.	-6.81 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	1.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	0.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	1.38

Application In Synthesis of [ 391-78-6 ]

* 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 [ 391-78-6 ]
Downstream synthetic route of [ 391-78-6 ]

[ 391-78-6 ] Synthesis Path-Upstream 1~1

1
[ 391-78-6 ]
[ 661463-17-8 ]

Yield	Reaction Conditions	Operation in experiment
79%	With phosphorus tribromide In N,N-dimethyl-formamide at 45 - 60℃; for 0.75 h;	To a solution of intermediate A.i (20 g, 122.58 mmol) in DMF (130 niL), heated to 60⁰C, was added phosphorous tribromide (13 mL, 1.15 eq.). The reaction was heated at 45°C for 45 min. After cooling to rt, the reaction was diluted with water (200 mL). Sat. Na₂CO₃ was added until pH 10 was reached. The solid was formed was filtered off. The solid was taken up in EA (200 mL) and the solution was concentrated to dryness. The residue was chromatographed (EA) to afford the title bromide as a yellowish solid (22 g, 79percent yield). ¹H NMR (CDCl₃) δ: 8.70 (d, J = 4.7 Hz, IH); 8.14 (m, IH); 7.96 (d, J = 4.7 Hz, IH); 7.81-7.73 (m, 2H).

References: [1] Patent: WO2008/152603, 2008, A1, . Location in patent: Page/Page column 36.
[2] Patent: WO2017/21319, 2017, A1, . Location in patent: Page/Page column 32.

[ 391-78-6 ] Synthesis Path-Downstream 1~35

1
[ 391-78-6 ]
[ 391-77-5 ]

Yield	Reaction Conditions	Operation in experiment
	With trichlorophosphate; In dichloromethane;	(b) 4-Chloro-6-fluoroquinoline A mixture of 52 g (0.319 mol) of <strong>[391-78-6]6-fluoro-4-hydroxyquinoline</strong> and 100 ml of phosphorus oxychloride was stirred and heated under reflux for 3 hr. The reaction mixture was concentrated in vacuo. A slurry of the residue in methylene chloride was poured into ice-water, and the mixture neutralized with 3N sodium hydroxide. The organic phase was separated, and the aqueous phase was extracted with 250 ml of methylene chloride twice. The organic phases were combined, washed with water, dired over sodium sulfate, and concentrated in vacuo. The residue was crystallized from hexane to give 27.95 g of product, mp 71°-74°.

References: [1]Journal of the American Chemical Society,1947,vol. 69,p. 371,373.
[2]Patent: US4560692,1985,A .

2
[ 391-78-6 ]
[ 147006-10-8 ]

References: [1]Heterocycles,1994,vol. 39,p. 693 - 722.

3
[ 391-78-6 ]
[ 391-36-6 ]

References: [1]Journal of the American Chemical Society,1947,vol. 69,p. 371,373.

4
[ 318-35-4 ]
[ 391-78-6 ]

References: [1]Journal of the American Chemical Society,1947,vol. 69,p. 371,373.

5
[ 26832-96-2 ]
[ 391-78-6 ]

References: [1]Journal of the American Chemical Society,1947,vol. 69,p. 371,373.

6
[ 391-78-6 ]
[ 74-88-4 ]
[ 108494-56-0 ]

Yield	Reaction Conditions	Operation in experiment
	With ammonia; potassium carbonate; In tetrahydrofuran; water;	(a) Iodomethane (6.9 ml) was added to a stirred suspension of <strong>[391-78-6]6-fluoro-4-hydroxyquinoline</strong> (16.3 g) and anhydrous potassium carbonate (15.2 g) in dry tetrahydrofuran (100 ml) at ambient temperature and stirring was continued for 18 hours. More iodomethane (1.8 ml) and anhydrous potassium carbonate (3.8 g) were added and stirring was continued for 4 hours at ambient temperature. Concentrated aqueous ammonia (specific gravity 0.88; 100 ml) was added and the mixture was evaporated to dryness. The residue was treated with water (200 ml) and extracted with dichloromethane (2*400 ml). The extract was dried and evaporated to dryness. The residue was crystallized from ethyl acetate to give the novel compound 6-fluoro-1-methyl-4-quinolone, m.p. 88-89.

References: [1]Journal of the American Chemical Society,2017,vol. 139,p. 8267 - 8276.
[2]Patent: US4772614,1988,A .

7
[ 391-78-6 ]
6-fluoro-4-hydroxy-3-hydroxymethylquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With formaldehyd; In sodium hydroxide;	(b) The starting material for the above preparation was prepared in a similar manner to that described in Example 3. <strong>[391-78-6]6-Fluoro-4-hydroxyquinoline</strong> was reacted with 40percent aqueous formaldehyde in aqueous sodium hydroxide solution to give the novel 6-fluoro-4-hydroxy-3-hydroxymethylquinoline m.p. 310°-315°.

References: [1]Patent: US4442109,1984,A .

8
[ 87-13-8 ]
[ 371-40-4 ]
[ 391-78-6 ]

Yield	Reaction Conditions	Operation in experiment
32%		To a suspension solution of 6-fluoroquinolin-4-ol (3.67 g, 22.5 mmol) (synthesized in overall yield of 32percent starting from 4-fluoroaniline and diethyl ethoxymethylenemalonate according to a literature procedure (see Price et al., Organic Syntheses, Coll. Vol. 3, p. 272; Vol. 28, p. 38), triphenylphosphine (6.56 g, 25 mmol), and 3-bromo-1-propanol (2.3 mL, 25 mmol) in dry tetrahydrofuran (30 mL) was added diisopropyl azodicarboxylate (4.9 mL, 25 mmol) at 25° C. over 30 minutes under nitrogen and the reaction mixture was left stirring for one hour. Hydrobromic acid (2.8 mL of 48percent aqueous solution, 25 mmol) was added, resulting in precipitation of the titled compound. The product was collected by suction filtration and washed with THF, acetone and ether to give a light yellow crystalline solid (4.17 g, 51percent). 1H NMR (400 MHz, DMSO-d6): 2.45 (2H, m), 3.82 (2H, t, J=6.5 Hz), 4.61 (2H, t, J=5.7 Hz), 7.64 (1H, d, J=6.6 Hz), 8.40 (1H, dt, J=8.5, 2.7 Hz), 7.90 (m, 1H), 8.27 (1H, dd, J=9.4, 4.8 Hz), 9.24 (1H, d, J=6.6 Hz).
	With hydrogenchloride; sodium hydroxide; In diphenylether; hexane; water;	(a) 6-Fluoro-4-hydroxyquinoline A mixture of 216 ml of diethyl ethoxymethylenemalonate, 95 ml of 4-fluoroaniline, and 800 ml of diphenyl ether was stirred and slowly heated to 185° with distillation of the ethanol formed. The reaction mixture was then heated to 245° for 1.5 hr. The total amount of ethanol collected was 105 ml. The reaction mixture was allowed to cool to 60° at which time 250 ml of hexane was added. After it had stood overnight, the product was collected, washed with hexane and dried to give 223 g of solid mp 305°-309°. A mixture of the above solid, 600 ml of 3N sodium hydroxide, and 250 ml of water was stirred and heated under reflux for 2 hr. To the hot brown cloudy mixture was slowly added 600 ml of 3N hydrochloric acid to precipitate the product, 6-fluoro-4-hydroxyquinoline-3-carboxylic acid. This product was filtered from the cooled reaction mixture. This damp solid and 600 ml of diphenyl ether was slowly heated to 250° while water was allowed to distill out. The reaction mixture was held at this temperature for 20 min. and then allowed to cool to 100°. Then 500 ml of hexane was added, and the mixture was stirred for 1 hr. The product 6-fluoro-4-hydroxyquinoline, was collected and washed with hexane to give 144 g, mp 209°-212°.

References: [1]Patent: US2009/99220,2009,A1 .Location in patent: Page/Page column 8-9.
[2]Patent: US4560692,1985,A .

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 2 - Step 2 and 3 A mixture of 94 g (0.4 mole) of ethyl 6-fluoro-4-hydroxyquinoline-3-carboxylate from example 1, 80 g (2.0 mole) of sodium hydroxide and 200 ml of water was heated to its reflux temperature and held at that temperature while stirring for 30 minutes. The hot solution was poured into a mixture of ice and hydrochloric acid. The acid solution was filtered, washed with water and suctioned dry. The solid obtained was dissolved in 200 ml of diphenyl ether, and the solution heated to its reflux temperature and maintained at reflux for less than 5 minutes. After cooling for several hours the solid precipitate was separated and washed with diethyl ether. The identity of the product, 6-fluoro-4-hydroxyquinoline, was confirmed by infrared and nuclear magnetic resonance spectral analyses.
		EXAMPLE 2 -- STEP 2 AND 3 A mixture of 94 g (0.4 mole) of ethyl 6-fluoro-4-hydroxyquinoline-3-carboxylate from example 1, 80 g (2.0 mole) of sodium hydroxide and 200 ml of water was heated to its reflux temperature and held at that temperature while stirring for 30 minutes. The hot solution was poured into a mixture of ice and hydrochloric acid. The acid solution was filtered, washed with water and suctioned dry. The solid obtained was dissolved in 200 ml of diphenyl ether, and the solution heated to its reflux temperature and maintained at reflux for less than 5 minutes. After cooling for several hours the solid precipitate was separated and washed with diethyl ether. The identity of the product, 6-fluoro-4-hydroxyquinoline, was confirmed by infrared and nuclear magnetic resonance spectral analyses.

10
[ 391-78-6 ]
4-fluoro-2-(1H-pyrazol-3-yl)aniline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		15) 1.2. 4-Fluoro-2-(1H-pyrazol-3-yl)aniline, m.p. 91°-92° C., from <strong>[391-78-6]6-fluoro-4-quinolinol</strong>.

References: [1]Patent: US5387585,1995,A .

11
[ 391-78-6 ]
[ 358-23-6 ]
[ 1072792-48-3 ]

Yield	Reaction Conditions	Operation in experiment
50%	With 2,6-dimethylpyridine;dmap; In dichloromethane; at 0℃;	17.i. Trifluoro-methanesulfonic acid 6-fluoro-quinolin-4-yl ester A mixture of <strong>[391-78-6]6-fluoro-quinolin-4-ol</strong> (2 g, 12.3 mmol), 2,6-lutidine (2.0 g. 18.4 mmol) and DMAP (0.15 g, 1.2 mmol) in DCM (50 mL) was cooled to 0° C. At this temperature, trifluoromethane sulfonic anhydride (3.9 g, 13.5 mmol) was added dropwise and the mixture stirred at 0° C. for 3 h. A sat. NH4Cl solution was added and the phases separated. The org. layer was washed with water, dried over MgSO4 and concentrated. Chromatography on SiO2 (DCM) gave the desired triflate (1.8 g, 50percent yield) as a brownish solid. 1H NMR (CDCl3) delta: 8.95 (d, J=5.0 Hz, 1H), 8.22 (dd, J=9.4, 5.3 Hz, 1H), 7.64 (m, 2H), 7.46 (d, J=5.0 Hz, 1H). MS (ESI, m/z): 296.0 [M+H+].
50%	With 2,6-dimethylpyridine; dmap; In dichloromethane; at 0℃; for 3h;	Example 17: (>7V-[(R>3-(2,3-dihydro-benzo[l,4]dioxin-6-yl)-2-oxo-oxazolidin- 5-ylmethyl]-3-(6-fluoro-quinolin-4-yl)-acrylamide:; 17.i. Trifluoro-methanesulfonic acid 6-fluoro-quinolin-4-yl ester:; A mixture of <strong>[391-78-6]6-fluoro-quinolin-4-ol</strong> (2 g, 12.3 mmol), 2,6-lutidine (2.0 g. 18.4 mmol) andDMAP (0.15 g, 1.2 mmol) in DCM (5O mL) was cooled to 00C. At this temperature, trifluoromethane sulfonic anhydride (3.9 g, 13.5 mmol) was added dropwise and the mixture stirred at 00C for 3 h. A sat. NH4Cl solution was added and the phases separated.The org. layer was washed with water, dried over MgSO4 and concentrated.Chromatography on SiO2 (DCM) gave the desired triflate (1.8 g, 50percent yield) as a brownish solid. 1H NMR (CDCl3) delta: 8.95 (d, J = 5.0 Hz, IH), 8.22 (dd, J = 9.4, 5.3 Hz, IH), 7.64 (m, 2H),7.46 (d, J = 5.0 Hz, IH).MS (ESI, m/z): 296.0 [M+H+].
47%	With triethylamine; In dichloromethane; at 0 - 20℃;Inert atmosphere;	To a solution of <strong>[391-78-6]6-fluoroquinolin-4-ol</strong> (10g, 61.3 mmol) in DCM (60 mL) and Et3N (12.5g, 122.6 mmol) was slowly dropwised Tf2O (21g, 73.56 mmol) at 0 under N2. The mixture was stirred overnight at r.t. The mixture was quenched by H2O (30 mL) and extracted with DCM (50 mL 3). The organic layer was dried over with Na2SO4, filtered and concentrated to give crude product which was further purified by column chromatography, eluting with EA: PE=1: 10 to give the product (8.56 g, 47percent). [M+H] +=296.

References: [1]Patent: US2010/137290,2010,A1 .Location in patent: Page/Page column 71.
[2]Patent: WO2008/126024,2008,A2 .Location in patent: Page/Page column 146.
[3]Patent: WO2018/54365,2018,A1 .Location in patent: Paragraph 0338; 0339; 0869; 0870.

12
[ 2033-24-1 ]
[ 371-40-4 ]
[ 391-78-6 ]

Yield	Reaction Conditions	Operation in experiment
46%		To a solution of p-fluoroaniline (3.03 mL, 31.5 mmol, 1 equiv) in ethanol (30 mL) were added Meldrum's acid (5.54 g, 38.4 mmol, 1.2 equiv) and triethyl orthoformate (12.4 mL, 74.5 mmol, 2.4 equiv). The mixture was heated to reflux for 2.5 h. The reaction was cooled to 0 °C and the solid was filtered and washed with cold ethanol. The dried solid was added portiowise over 5 mins to boiling diphenyl ether (100 mL). Reflux was maintained for an additional 3 mins. The reaction was stirred at room temperature for 30 mins before petroleum ether (25 mL) was added and the solid was filtered and dried. The crude product was purified by column chromatography on silica gel (EtOAc/MeOH 95:5), to afford 6-fluoroquinolin-4-ol (2.36 g, 14.5 mmol, 46percent). The analyses were consistent with the data reported in the literature. Ref: WO2010/123995 (2010) TLC Rf 0.41 (EtOAc/MeOH 95:5) 1HNMR (400MHz, DMSO-de) delta (ppm) 11.90 (s, 1H, OH), 7.94 (d, J=7.6, 1H, NCH), 7.73 (m, 1H, NCCH), 7.53-7.67 (m, 2H, FCCH, FCCH), 6.04 (d, J=7.3, 1H, OHCCH) ppm CNMR (101 MHz, DMSO-de) delta (ppm) 159.9 (7), 157.7 (5), 140.0 (2), 137.2 (10), 127.3 (4), 121.1 (6), 120.8 (1), 109.5 (3), 108.3 (8) ppm IR (neat) v max 2768 (br), 1594 (m) cm"1 LCMS (ESI+) m/z 164.1 [M+H]+, 186.1 [M+Na]+ 11 RMS (ESI+) m/z calcd. 164.0506 m/z meas. 164.0509 [M+H] Mpt 227 - 228 °C
	With orthoformic acid triethyl ester; In ethanol; for 2.5h;Heating / reflux;	To a mixture of 4-fluoro-aniline (25.O g, 224.9 mmol) in EtOH (17O mL) were added successively Meldrum's acid (35.69 g, 247.6 mmol) and triethyl orthoformate (40.O mL, 240.4 mmol). The reaction mixture was then refluxed for 2 h 30 min. The reaction mixture was cooled to 00C and the solid was filtered and washed with cold EtOH. The solid was dried under HV to give 54.62 g of a yellow powder. To a boiling solution of diphenyl ether (230 g) was added the latter solid portion wise over 5 min. The reflux was maintained for further 3 min and the reaction mixture was allowed to stir at rt. After 30 min at rt, ether was added and the desired solid was filtered, thoroughly washed with ether and dried under HV to afford the title compound as a brown solid (11.11 g, 68.1 mmol). MS (ESI, mix): 164.1 [M+H+].

References: [1]Patent: WO2017/21319,2017,A1 .Location in patent: Page/Page column 31.
[2]Patent: WO2008/152603,2008,A1 .Location in patent: Page/Page column 36.

13
[ 391-78-6 ]
[ 627-18-9 ]
[ 1142407-71-3 ]

Yield	Reaction Conditions	Operation in experiment
51%		To a suspension solution of <strong>[391-78-6]6-fluoroquinolin-4-ol</strong> (3.67 g, 22.5 mmol) (synthesized in overall yield of 32percent starting from 4-fluoroaniline and diethyl ethoxymethylenemalonate according to a literature procedure (see Price et al., Organic Syntheses, Coll. Vol. 3, p. 272; Vol. 28, p. 38), triphenylphosphine (6.56 g, 25 mmol), and 3-bromo-1-propanol (2.3 mL, 25 mmol) in dry tetrahydrofuran (30 mL) was added diisopropyl azodicarboxylate (4.9 mL, 25 mmol) at 25° C. over 30 minutes under nitrogen and the reaction mixture was left stirring for one hour. Hydrobromic acid (2.8 mL of 48percent aqueous solution, 25 mmol) was added, resulting in precipitation of the titled compound. The product was collected by suction filtration and washed with THF, acetone and ether to give a light yellow crystalline solid (4.17 g, 51percent). 1H NMR (400 MHz, DMSO-d6): 2.45 (2H, m), 3.82 (2H, t, J=6.5 Hz), 4.61 (2H, t, J=5.7 Hz), 7.64 (1H, d, J=6.6 Hz), 8.40 (1H, dt, J=8.5, 2.7 Hz), 7.90 (m, 1H), 8.27 (1H, dd, J=9.4, 4.8 Hz), 9.24 (1H, d, J=6.6 Hz).

References: [1]Patent: US2009/99220,2009,A1 .Location in patent: Page/Page column 8-9.

14
[ 391-78-6 ]
N-(but-3-yn-1-yl)-6-fluoroquinolin-4-amine [ No CAS ]

References: [1]Patent: WO2017/21319,2017,A1 .

15
[ 391-78-6 ]
methyl 3-(benzyloxy)-6-(4-((6-fluoroquinolin-4-yl)amino)but-1-yn-1-yl)picolinate [ No CAS ]

References: [1]Patent: WO2017/21319,2017,A1 .

16
[ 391-78-6 ]
methyl 6-(4-((6-fluoroquinolin-4-yl)amino)butyl)-3-hydroxypicolinate [ No CAS ]

References: [1]Patent: WO2017/21319,2017,A1 .

17
[ 391-78-6 ]
(E)-6-(4-((6-fluoroquinolin-4-yl)amino)butyl)-3-hydroxypicolinaldehyde oxime [ No CAS ]

References: [1]Patent: WO2017/21319,2017,A1 .

18
[ 391-78-6 ]
C₂₆H₃₄FN₃O₃Si [ No CAS ]

References: [1]Patent: WO2017/21319,2017,A1 .

19
[ 391-78-6 ]
C₁₉H₁₈FN₃O₂ [ No CAS ]

References: [1]Patent: WO2017/21319,2017,A1 .

20
[ 391-78-6 ]
[ 123084-61-7 ]
2-fluoro-11-methyl-7H-chromeno[3,2-c]quinoline [ No CAS ]

References: [1]Advanced Synthesis and Catalysis,2017,vol. 359,p. 3299 - 3303.

21
[ 391-78-6 ]
6-fluoro-4-(1,4-dioxaspiro[4.5]indole-7-en-8-yl)quinoline [ No CAS ]