[ CAS No. 60186-15-4 ]

Name: 60186-15-4|2,4-Difluoro-5-nitropyridine|96%
Brand: Ambeed
SKU: A259785
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Quality Control of [ 60186-15-4 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 60186-15-4 ]

SDS Specification

Alternatived Products of [ 60186-15-4 ]

Product Details of [ 60186-15-4 ]

CAS No. :	60186-15-4	MDL No. :	MFCD18802741
Formula :	C₅H₂F₂N₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	OLPMWQXRTRVQRS-UHFFFAOYSA-N
M.W :	160.08	Pubchem ID :	12275767
Synonyms :

Calculated chemistry of [ 60186-15-4 ]

Physicochemical Properties

Num. heavy atoms :	11
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	5.0
Num. H-bond donors :	0.0
Molar Refractivity :	32.98
TPSA :	58.71 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.41 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.87
Log Po/w (XLOGP3) :	1.22
Log Po/w (WLOGP) :	2.11
Log Po/w (MLOGP) :	0.95
Log Po/w (SILICOS-IT) :	0.15
Consensus Log Po/w :	1.06

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.94
Solubility :	1.84 mg/ml ; 0.0115 mol/l
Class :	Very soluble
Log S (Ali) :	-2.05
Solubility :	1.43 mg/ml ; 0.00891 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-1.95
Solubility :	1.78 mg/ml ; 0.0111 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	3.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.21

Safety of [ 60186-15-4 ]

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 [ 60186-15-4 ]

* 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 [ 60186-15-4 ]
Downstream synthetic route of [ 60186-15-4 ]

[ 60186-15-4 ] Synthesis Path-Upstream 1~1

1
[ 4487-56-3 ]
[ 60186-15-4 ]

Yield	Reaction Conditions	Operation in experiment
85%	With potassium fluoride; 18-crown-6 ether In 1-methyl-pyrrolidin-2-one at 100℃; for 3 h; Inert atmosphere	2,4-Difluoro-5-nitropyridine.In a 250 mL round-bottom flask was added 2,4- dichloro-5-nitropyridine (0.73 g,3.8 mmol), potassium fluoride (0.659 g, 11.3 mmol), and 18-crown-6 (0.160 g,0.605 mmol) in N-methylpyrrolidinone (3 mL) to give a tan suspension. Themixture was heated at 100°C under nitrogen for 3 h. The mixture was thenpartitioned between water and ether/hexane. The organic layer was washed withwater, brine, dried and concentrated to give a tan solid (0.515 g, 85percent): 1H NMR(400 MHz, CDC13) δ 9.07 (d, J = 9.7 Hz, 1H), 6.96 (dd, J = 9.5, 2.5 Hz,1H);19F NMR (376 MHz, CDC13) δ -52.20 (d, J = 29.3 Hz), -98.13 (d, J = 28.9 Hz).
79%	With potassium fluoride; 18-crown-6 ether In 1-methyl-pyrrolidin-2-one at 100℃; for 3 h; Inert atmosphere	Sledeski, A.W.; Kubiak, G.G. ; O'Brien, M.K. : Powers, M.R.; Powner, T.H. ; Truesdale, L.K. J. Org. Chem. 2000, 65, 8114-8118. In a 250 mL round-bottomed flask was 2,4-dichloro-5-nitropyridine (4.27 g, 22.13 mmol), (0082) POTASSIUM FLUORIDE (3.86 g, 66.4 mmol), and 18C6 (0.936 g, 3.54 mmol) in NMP (15 mL) to give a tan suspension. The mixture was heated at 100°C under nitrogen for 3 h. LCMS showed complete conversion to a new peak. The mixture was then partitioned between water and ether (with some hexane: better for getting rid of NMP). The organic layer was washed with water, brine, dried and concentrated to a tan oil. It became solid (2.8 g, 79percent) when cooled in frige. The material was used as is.
47%	With potassium fluoride; 18-crown-6 ether In 1-methyl-pyrrolidin-2-one at 100℃; for 2 h; Inert atmosphere	A mixture of 2,4-dichloro-5-nitropyridine (450 mg, 2.332 mmol), potassium fluoride (406 mg, 7.00 mmol), and 18-Crown-6 (99 mg, 0.373 mmol) in NMP (2 mL) was heated at 100°C under nitrogen for 2 h. The reaction mixture was transferred to a separatory funnel containing water (5 mL) and ether (50 mL). The layers were separated and the organic layer was washed with water (2 x 5 mL), brine (5 mL), dried over MgS04, filtered, and concentrated. The residue was purified by column chromatography on silica gel (10percent→ 20percent ethyl acetate in hexanes; 40 g column) to afford 2,4-difluoro-5-nitropyridine (177 mg, 1.106 mmol, 47percent yield) as a colorless solid: NMR (400MHz, CDCh) δ 9.07 (d, J=9.5 Hz, 1H), 6.95 (dd, J=9A, 2.4 Hz, 1H); ¹⁹F NMR (376MHz, CDCh) δ -52.17 (d, J=27.7 Hz, IF), -98.12 (dt, J=29.5, 8.7 Hz, IF).

Reference： [1] Patent: WO2015/69594, 2015, A1, . Location in patent: Page/Page column 106
[2] Patent: WO2018/98413, 2018, A1, . Location in patent: Page/Page column 16
[3] Patent: WO2018/98411, 2018, A1, . Location in patent: Page/Page column 94; 95

[ 60186-15-4 ] Synthesis Path-Downstream 1~37

2
[ 60186-15-4 ]
6-fluoro-4-(2,2,2-trifluoroethoxy)pyridin-3-amine [ No CAS ]

Reference： [1]Patent: WO2015/69594,2015,A1

3
[ 60186-15-4 ]
6-fluoro-4-morpholinopyridin-3-amine [ No CAS ]

Reference： [1]Patent: WO2015/69594,2015,A1

4
[ 60186-15-4 ]
[ 75-89-8 ]
2-fluoro-5-nitro-4-(2,2,2-trifluoroethoxy)pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In tetrahydrofuran; at 0 - 20℃; for 5.58333h;	2-Fluoro-5-nitro-4-(2,2,2-trifluoroethoxy)pyridine.A solution of 2,4-difluoro-5- nitropyridine (0.1523 g, 0.951 mmol) intetrahydrofuran (2 mL) was cooled to 0 C. 2,2,2-Trifluoroethanol (0.082mL, 1.142 mmol) was added to the mixture. After 5 min, triethylamine (0.265 mL,1.903 mmol) was added. The reaction was stirred at 0 C for 1 h, and thenallowed to warm to rt. The reaction was stirred at rt for 4.5 h. The solventwas removed in vacuo and the crude product carried on without furtherpurification.

Reference： [1]Patent: WO2015/69594,2015,A1 .Location in patent: Page/Page column 95; 101

5
[ 110-91-8 ]
[ 60186-15-4 ]
4-(2-fluoro-5-nitropyridin-4-yl)morpholine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With triethylamine; In tetrahydrofuran; at -40 - 0℃; for 3.0h;	4-(2-Fluoro-5-nitropyridin-4-yl)morpholine. In a 50 mL round-bottom flask vial was dissolved <strong>[60186-15-4]2,4-difluoro-5-nitropyridine</strong> (175.7 mg, 1.098 mmol) in tetrahydrofuran (5 mL) to give a tan solution. After cooling to -40C, morpholine (0.080 mL, 0.918 mmol) was added, followed by Et3N (0.256 mL, 1.83 mmol). The cloudy yellow mixture was stirred at-40 C - 0C for 3 h. The mixture was concentrated togive a yellow solid. The solid was purified by flash column chromatography on silica gel, eluting with 60% ethyl acetate/hexane, to afford the desired product (209 mg, 100%) as a yellow solid: 1H NMR (400 MHz, Chloroform- d) delta 8.60 (s, 1H), 6.42 (s, 1H), 3.96 - 3.81 (m, 4H), 3.33 - 3.18 (m, 4H);19F NMR (376 MHz, Chloroform-d) delta -61.42.

Reference： [1]Patent: WO2015/69594,2015,A1 .Location in patent: Page/Page column 106; 107

6
[ 4487-56-3 ]
[ 60186-15-4 ]

Yield	Reaction Conditions	Operation in experiment
85%	With potassium fluoride; 18-crown-6 ether; In 1-methyl-pyrrolidin-2-one; at 100℃; for 3h;Inert atmosphere;	2,4-Difluoro-5-nitropyridine.In a 250 mL round-bottom flask was added 2,4- dichloro-5-nitropyridine (0.73 g,3.8 mmol), potassium fluoride (0.659 g, 11.3 mmol), and 18-crown-6 (0.160 g,0.605 mmol) in N-methylpyrrolidinone (3 mL) to give a tan suspension. Themixture was heated at 100°C under nitrogen for 3 h. The mixture was thenpartitioned between water and ether/hexane. The organic layer was washed withwater, brine, dried and concentrated to give a tan solid (0.515 g, 85percent): 1H NMR(400 MHz, CDC13) delta 9.07 (d, J = 9.7 Hz, 1H), 6.96 (dd, J = 9.5, 2.5 Hz,1H);19F NMR (376 MHz, CDC13) delta -52.20 (d, J = 29.3 Hz), -98.13 (d, J = 28.9 Hz).
79%	With potassium fluoride; 18-crown-6 ether; In 1-methyl-pyrrolidin-2-one; at 100℃; for 3h;Inert atmosphere;	Sledeski, A.W.; Kubiak, G.G. ; O'Brien, M.K. : Powers, M.R.; Powner, T.H. ; Truesdale, L.K. J. Org. Chem. 2000, 65, 8114-8118. In a 250 mL round-bottomed flask was <strong>[4487-56-3]2,4-dichloro-5-nitropyridine</strong> (4.27 g, 22.13 mmol), (0082) POTASSIUM FLUORIDE (3.86 g, 66.4 mmol), and 18C6 (0.936 g, 3.54 mmol) in NMP (15 mL) to give a tan suspension. The mixture was heated at 100°C under nitrogen for 3 h. LCMS showed complete conversion to a new peak. The mixture was then partitioned between water and ether (with some hexane: better for getting rid of NMP). The organic layer was washed with water, brine, dried and concentrated to a tan oil. It became solid (2.8 g, 79percent) when cooled in frige. The material was used as is.
47%	With potassium fluoride; 18-crown-6 ether; In 1-methyl-pyrrolidin-2-one; at 100℃; for 2h;Inert atmosphere;	A mixture of <strong>[4487-56-3]2,4-dichloro-5-nitropyridine</strong> (450 mg, 2.332 mmol), potassium fluoride (406 mg, 7.00 mmol), and 18-Crown-6 (99 mg, 0.373 mmol) in NMP (2 mL) was heated at 100°C under nitrogen for 2 h. The reaction mixture was transferred to a separatory funnel containing water (5 mL) and ether (50 mL). The layers were separated and the organic layer was washed with water (2 x 5 mL), brine (5 mL), dried over MgS04, filtered, and concentrated. The residue was purified by column chromatography on silica gel (10percent? 20percent ethyl acetate in hexanes; 40 g column) to afford 2,4-difluoro-5-nitropyridine (177 mg, 1.106 mmol, 47percent yield) as a colorless solid: NMR (400MHz, CDCh) delta 9.07 (d, J=9.5 Hz, 1H), 6.95 (dd, J=9A, 2.4 Hz, 1H); 19 F NMR (376MHz, CDCh) delta -52.17 (d, J=27.7 Hz, IF), -98.12 (dt, J=29.5, 8.7 Hz, IF).

Reference： [1]Patent: WO2015/69594,2015,A1 .Location in patent: Page/Page column 106
[2]Patent: WO2018/98413,2018,A1 .Location in patent: Page/Page column 16
[3]Patent: WO2018/98411,2018,A1 .Location in patent: Page/Page column 94; 95

7
[ 60186-15-4 ]
6-fluoro-4-(2-vinylmorpholino)pyridin-3-amine [ No CAS ]