[ CAS No. 399-88-2 ] {[proInfo.proName]}

Name: 399-88-2|3-Fluoro-4-methylpyridine|97%
Brand: Ambeed
SKU: A205371
Price: 6.0 USD
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3d Animation Molecule Structure of 399-88-2

Structure of 399-88-2 * Storage: {[proInfo.prStorage]}

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Quality Control of [ 399-88-2 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 399-88-2 ]

SDS Specification

Alternatived Products of [ 399-88-2 ]

Product Details of [ 399-88-2 ]

CAS No. :	399-88-2	MDL No. :	MFCD04114226
Formula :	C₆H₆FN	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	WZMOEPZZTTWDIA-UHFFFAOYSA-N
M.W :	111.12	Pubchem ID :	345367
Synonyms :

Calculated chemistry of [ 399-88-2 ]

Physicochemical Properties

Num. heavy atoms :	8
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.17
Num. rotatable bonds :	0
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	29.16
TPSA :	12.89 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) :	-6.04 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.61
Log Po/w (XLOGP3) :	1.32
Log Po/w (WLOGP) :	1.95
Log Po/w (MLOGP) :	1.24
Log Po/w (SILICOS-IT) :	2.28
Consensus Log Po/w :	1.68

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	2.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-1.92
Solubility :	1.35 mg/ml ; 0.0121 mol/l
Class :	Very soluble
Log S (Ali) :	-1.19
Solubility :	7.15 mg/ml ; 0.0643 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.63
Solubility :	0.261 mg/ml ; 0.00235 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.21

Safety of [ 399-88-2 ]

Signal Word:	Danger	Class:	3
Precautionary Statements:	P261-P305+P351+P338	UN#:	1993
Hazard Statements:	H225-H315-H319-H335	Packing Group:	Ⅲ
GHS Pictogram:

Application In Synthesis of [ 399-88-2 ]

* 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 [ 399-88-2 ]
Downstream synthetic route of [ 399-88-2 ]

[ 399-88-2 ] Synthesis Path-Upstream 1~11

1
[ 372-47-4 ]
[ 74-88-4 ]
[ 399-88-2 ]

Yield	Reaction Conditions	Operation in experiment
47%	Stage #1: With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78 - 25℃; for 2 h; Stage #2: With sodium hydrogencarbonate In tetrahydrofuran; hexane; water	3-Fluoro-4-methylpyridine To a cooled (-78⁰C) solution of Λ/,Λ/-diisopropylamine (15.92mL, 113.4mmol) in THF (14OmL) a solution of BuLi 2.5M in hexane (45.4ml, 113.4 mmol) was added dropwise over 30 minutes under an atmosphere of Argon. The mixture was stirred for 30 min. at - 78⁰C and a solution of 3-fluoropyridine (1 Og₁ 103.1 mmol) in THF (5ml) was added. After 1h at -78⁰C, the mixture was treated with MeI (7 ml, 113.4mmol) and then was allowed to reach 25⁰C. A solution of NaHCO₃ saturated (30ml) was added and the aqueous phase was extracted with diethyl ether. The organic layer was dried (MgSO₄) and upon distillation the product was collected as a colourless liquid, bp 130⁰C, yield 5.3 g (47percent) δ 1 H-NMR (CDCI₃): 8.25 (s, 1 H), 8.18 (m, 1 H), 7.02 (m, 1 H). ESI/MS m/e: 112 ([M+H]+, C₆H₆FN)

Reference： [1] Patent: WO2007/17096, 2007, A1, . Location in patent: Page/Page column 70-71
[2] Journal of Medicinal Chemistry, 2003, vol. 46, # 4, p. 461 - 473
[3] Patent: US6455532, 2002, B1,
[4] Patent: US6350745, 2002, B1, . Location in patent: Page column 15;16
[5] Patent: WO2006/35967, 2006, A1, . Location in patent: Page/Page column 98-99

2
[ 3430-27-1 ]
[ 399-88-2 ]

Reference： [1] Journal of Fluorine Chemistry, 2011, vol. 132, # 8, p. 541 - 547

3
[ 23056-33-9 ]
[ 399-88-2 ]

Reference： [1] Journal of Organic Chemistry, 1955, vol. 20, p. 1729,1731

4
[ 21901-41-7 ]
[ 399-88-2 ]

Reference： [1] Journal of Organic Chemistry, 1955, vol. 20, p. 1729,1731

5
[ 21901-40-6 ]
[ 399-88-2 ]

Reference： [1] Journal of Organic Chemistry, 1955, vol. 20, p. 1729,1731

6
[ 6635-86-5 ]
[ 399-88-2 ]

Reference： [1] Journal of Organic Chemistry, 1955, vol. 20, p. 1729,1731

7
[ 21901-18-8 ]
[ 399-88-2 ]

Reference： [1] Journal of Organic Chemistry, 1955, vol. 20, p. 1729,1731

8
[ 23056-39-5 ]
[ 399-88-2 ]

Reference： [1] Journal of Organic Chemistry, 1955, vol. 20, p. 1729,1731

9
[ 695-34-1 ]
[ 399-88-2 ]

Reference： [1] Journal of Fluorine Chemistry, 2011, vol. 132, # 8, p. 541 - 547

10
[ 399-88-2 ]
[ 393-53-3 ]

Reference： [1] Journal of Organic Chemistry, 1955, vol. 20, p. 1729,1731

11
[ 399-88-2 ]
[ 40273-47-0 ]

Reference： [1] Journal of Fluorine Chemistry, 2011, vol. 132, # 8, p. 541 - 547

[ 399-88-2 ] Synthesis Path-Downstream 1~72

1
[ 399-88-2 ]
[ 393-53-3 ]

Reference： [1]Journal of Organic Chemistry,1955,vol. 20,p. 1729,1731

3
[ 3430-27-1 ]
aq.-ethanolic tetrafluoroboric acid [ No CAS ]
[ 399-88-2 ]

Reference： [1]Journal of Organic Chemistry,1955,vol. 20,p. 1729,1731

4
[ 372-47-4 ]
[ 74-88-4 ]
[ 399-88-2 ]

Yield	Reaction Conditions	Operation in experiment
47%		3-Fluoro-4-methylpyridine To a cooled (-780C) solution of Lambda/,Lambda/-diisopropylamine (15.92mL, 113.4mmol) in THF (14OmL) a solution of BuLi 2.5M in hexane (45.4ml, 113.4 mmol) was added dropwise over 30 minutes under an atmosphere of Argon. The mixture was stirred for 30 min. at - 780C and a solution of 3-fluoropyridine (1 Og1 103.1 mmol) in THF (5ml) was added. After 1h at -780C, the mixture was treated with MeI (7 ml, 113.4mmol) and then was allowed to reach 250C. A solution of NaHCO3 saturated (30ml) was added and the aqueous phase was extracted with diethyl ether. The organic layer was dried (MgSO4) and upon distillation the product was collected as a colourless liquid, bp 1300C, yield 5.3 g (47percent) delta 1 H-NMR (CDCI3): 8.25 (s, 1 H), 8.18 (m, 1 H), 7.02 (m, 1 H). ESI/MS m/e: 112 ([M+H]+, C6H6FN)
	With diisopropylamine;	3-Fluoro-4-methylpyridine (5-1) To a stirred solution of LDA (5.5 mmol) at -78° C., was added 3-fluoropyridine (486 mg, 5.0 mmol) dropwise. After stirring for 4h at -78° C., methyl iodide was added dropwise (0.343 mL, 5.5 mmol). The reaction was quenched after stirring at -78° C. for 2 h, by the addition of 20 mL of sat. aq. NH4Cl. This mixture was extracted with EtOAc (3*25 mL), the combined organics dried and concentrated to afford the product as a yellow solid 5-1: 1H NMR (CDCl3) delta 8.36 (br s, 1H), 8.27 (d, 1H, 4.8 Hz), 7.15 (br dd, 1H, 5.7, 5.7 Hz), 2.32 (s, 3H).
		To a solution of diisopropylamine in THF (200 mL) was added a 2.44 M H-BuLi in THF (116 mL) at 0 0C and the mixture was stirred at 0 0C for 20 min. The mixture was cooled to -60 0C and a solution of 3-fluoropyridine (25.0 g) in THF (100 mL) was added. The mixture was stirred at -60 0C for 3 h and a solution of iodomethane (17.6 mL) in THF (100 mL) was added. The mixture was stirred at -60 0C for 30 min and the reaction was quenched with saturated aqueous NH4CI (100 mL). The aqueous layer was extracted with EtOAc (three times). The combined organic layer was dried over MgSO4, filtered, concentrated under reduced pressure to give a colorless oil (14.6 g). To a solution of the above oil (14.6 g) in CHCl3 (145 mL) was added a suspension of m-chloroperbenzoic acid (34.8 g) in CHCl3 (145 mL) at 0 0C and the mixture was stirred at ambient temperature for 3 h. To the mixture was added saturated aqueous Na2S2psi3 and the organic layer was separated. The aqueous layer was extracted with CHCl3 (three times). The combined organic layer was washed with IM aqueous NaOH and saturated aqueous NaCl, dried over MgSO4, filtered, concentrated under reduced pressure EPO <DP n="102"/>and purified by medium-pressure liquid chromatography (silica gel, 2percent to 4percent MeOH in CHCl3) to give the title compound (3.47 g).1HNMR (SOO MHz, CDCl3, delta): 2.28-2.32 (m, 3H), 7.06-7.13 (m, IH), 7.96-8.00 (m, IH), 8.11 (dd,J= 4.9, 1.8 Hz, IH); ESI MS m/z 150 (M++23, 100percent).

Reference： [1]Patent: WO2007/17096,2007,A1 .Location in patent: Page/Page column 70-71
[2]Journal of Medicinal Chemistry,2003,vol. 46,p. 461 - 473
[3]Patent: US6455532,2002,B1
[4]Patent: US6350745,2002,B1 .Location in patent: Page column 15;16
[5]Patent: WO2006/35967,2006,A1 .Location in patent: Page/Page column 98-99

5
[ 399-88-2 ]
[ 33252-59-4 ]

Yield	Reaction Conditions	Operation in experiment
	With 3-chloro-benzenecarboperoxoic acid; In chloroform; at 0 - 20℃; for 3h;	To a solution of diisopropylamine in THF (200 mL) was added a 2.44 M H-BuLi in THF (116 mL) at 0 0C and the mixture was stirred at 0 0C for 20 min. The mixture was cooled to -60 0C and a solution of 3-fluoropyridine (25.0 g) in THF (100 mL) was added. The mixture was stirred at -60 0C for 3 h and a solution of iodomethane (17.6 mL) in THF (100 mL) was added. The mixture was stirred at -60 0C for 30 min and the reaction was quenched with saturated aqueous NH4CI (100 mL). The aqueous layer was extracted with EtOAc (three times). The combined organic layer was dried over MgSO4, filtered, concentrated under reduced pressure to give a colorless oil (14.6 g). To a solution of the above oil (14.6 g) in CHCl3 (145 mL) was added a suspension of m-chloroperbenzoic acid (34.8 g) in CHCl3 (145 mL) at 0 0C and the mixture was stirred at ambient temperature for 3 h. To the mixture was added saturated aqueous Na2S2psi3 and the organic layer was separated. The aqueous layer was extracted with CHCl3 (three times). The combined organic layer was washed with IM aqueous NaOH and saturated aqueous NaCl, dried over MgSO4, filtered, concentrated under reduced pressure EPO <DP n="102"/>and purified by medium-pressure liquid chromatography (silica gel, 2percent to 4percent MeOH in CHCl3) to give the title compound (3.47 g).1HNMR (SOO MHz, CDCl3, delta): 2.28-2.32 (m, 3H), 7.06-7.13 (m, IH), 7.96-8.00 (m, IH), 8.11 (dd,J= 4.9, 1.8 Hz, IH); ESI MS m/z 150 (M++23, 100percent).

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 461 - 473
[2]Patent: WO2006/35967,2006,A1 .Location in patent: Page/Page column 98-99
[3]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 3636 - 3643

6
[ 399-88-2 ]
[ 312904-99-7 ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 461 - 473

7
[ 399-88-2 ]
2-aminomethyl-3-fluoro-4-methylpyridine dihydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 461 - 473

8
[ 399-88-2 ]
3-Fluoro-4-methyl-2-pyridylmethyl 3-(2,2-difluoro-2-(2-pyridyl)ethylamino)-6-chloropyrazin-2-one-1-acetamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 461 - 473

9
[ 399-88-2 ]
2-[3-(2,2-difluoro-2-pyridin-2-yl-ethylamino)-6-methyl-2-oxo-2H-pyrazin-1-yl]-N-(3-fluoro-4-methyl-pyridin-2-ylmethyl)-acetamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 461 - 473

10
[ 399-88-2 ]
2-[3-(2,2-difluoro-2-phenyl-ethylamino)-6-methyl-2-oxo-2H-pyrazin-1-yl]-N-(3-fluoro-4-methyl-pyridin-2-ylmethyl)-acetamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 461 - 473

11
[ 399-88-2 ]
3-fluoro-4-methyl-2-pyridylmethyl 3-(2,2-difluoro-2-(2-pyridyl)ethylamino)-6-cyanopyrazin-2-one-1-acetamide hydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 461 - 473

12
[ 399-88-2 ]
[ 343-72-6 ]

Reference： [1]Journal of Organic Chemistry,1955,vol. 20,p. 1729,1731

13
[ 23056-33-9 ]
[ 399-88-2 ]

Reference： [1]Journal of Organic Chemistry,1955,vol. 20,p. 1729,1731

14
[ 21901-41-7 ]
[ 399-88-2 ]

Reference： [1]Journal of Organic Chemistry,1955,vol. 20,p. 1729,1731

15
[ 21901-40-6 ]
[ 399-88-2 ]

Reference： [1]Journal of Organic Chemistry,1955,vol. 20,p. 1729,1731

16
[ 6635-86-5 ]
[ 399-88-2 ]

Reference： [1]Journal of Organic Chemistry,1955,vol. 20,p. 1729,1731

17
[ 21901-18-8 ]
[ 399-88-2 ]

Reference： [1]Journal of Organic Chemistry,1955,vol. 20,p. 1729,1731

18
[ 23056-39-5 ]
[ 399-88-2 ]

Reference： [1]Journal of Organic Chemistry,1955,vol. 20,p. 1729,1731

19
[ 399-88-2 ]
DCM-MeOH [ No CAS ]
[ 33252-59-4 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate; 3-chloro-benzenecarboperoxoic acid; In dichloromethane; water;	3-Fluoro-4-methylpyridine-N-oxide. (5-2) To a stirred solution of 3.17 g (28.6 mmol) of <strong>[399-88-2]3-fluoro-4-methylpyridine</strong> in 5-1 35 mL of dichloromethane was added 4.83 g NaHCO3 (57.5 mmol, in 10 mL H2O). This mixture was cooled to 0° C., and 9.85 g of MCPBA (57.1 mmol) was added in three portions over 15 min. The reaction was allowed to warm to room temperature overnight. The layers of the biphasic mixture were separated and the aqueous phase was washed with chloroform (3*100 mL). The combined organic layers were dried over MgSO4 and the solvents removed at reduced pressure to give an oil that was chromatographed on SiO2 using 95:5 DCM-MeOH to give 5-2 as a white solid: 1H NMR (CDCl3) delta 8.13 (d, 1H, 4.6 Hz), 7.99 (d, 1H, 6.6 Hz), 7.09 (br dd, 1H, 7.6, 7.6 Hz), 2.30 (s, 3H).

Reference： [1]Patent: US6455532,2002,B1

20
[ 399-88-2 ]
[ 7677-24-9 ]
[ 312904-99-7 ]

Reference： [1]Patent: US6350745,2002,B1 .Location in patent: Page column 16

21
[ 695-34-1 ]
[ 399-88-2 ]

Reference： [1]Journal of Fluorine Chemistry,2011,vol. 132,p. 541 - 547

22
[ 399-88-2 ]
[ 471909-36-1 ]

Reference： [1]Journal of Fluorine Chemistry,2011,vol. 132,p. 541 - 547

23
[ 399-88-2 ]
[ 40273-47-0 ]

Reference： [1]Journal of Fluorine Chemistry,2011,vol. 132,p. 541 - 547

24
[ 399-88-2 ]
[ 100-52-7 ]
[ 177600-62-3 ]

Reference： [1]Journal of Fluorine Chemistry,2011,vol. 132,p. 541 - 547

25
[ 3430-27-1 ]
[ 399-88-2 ]

Reference： [1]Journal of Fluorine Chemistry,2011,vol. 132,p. 541 - 547

26
[ 399-88-2 ]
[ 451-46-7 ]
[ 1383377-54-5 ]

Yield	Reaction Conditions	Operation in experiment
89%		Step 6: Preparation of 1-(4-fluorophenyl)-2-(3-fluoropyridin-4-yl)ethanoneLithium hexamethyldisilazide (1.0M in THF, 17.9 mL, 17.9 mmol) was cooled to 0° C. and <strong>[399-88-2]3-fluoro-4-methylpyridine</strong> (1.00 g, 0.926 mmol) in THF (50 mL) was added dropwise, keeping the solution temperature below 5° C. The mixture was then stirred for 1 hour at 0° C. and ethyl 4-fluorobenzoate in THF (50 mL) was added dropwise. The reaction was allowed to warm slowly to rt with stirring overnight. Aqueous ammonium chloride was added and the mixture was poured into EtOAc. The organic phase was separated dried (Na2SO4) and concentrated. Silica gel chromatography using a 10-50percent EtOAc/heptanes gradient yielded 1.83 g (89percent) of Ex 1-Step 6 product as a white solid: LCMS m/z 234.4 (M+1); 1H NMR (400 MHz, MeOH-d4) delta 8.41 (d, J=1.7 1H), 8.32 (d, J=4.8, 1H), 8.14 (dd, J=8.9, 5.4, 2H), 7.38 (dd, J=5.9, 5.1, 1H), 7.25 (dd, J=9.0, 9.0, 2H), 4.52 (s, 2H).

Reference： [1]Patent: US2012/157440,2012,A1 .Location in patent: Page/Page column 27

27
[ 399-88-2 ]
[ 1383376-92-8 ]