[ CAS No. 4278-08-4 ] {[proInfo.proName]}

Name: 4278-08-4|2-(4-Fluorophenyl)-1H-imidazole|97%
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SKU: A226458
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Quality Control of [ 4278-08-4 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 4278-08-4 ]

SDS Specification

Alternatived Products of [ 4278-08-4 ]

Product Details of [ 4278-08-4 ]

CAS No. :	4278-08-4	MDL No. :	MFCD04114652
Formula :	C₉H₇FN₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	GTIYLLQEFVPNTN-UHFFFAOYSA-N
M.W :	162.16	Pubchem ID :	11744944
Synonyms :

Calculated chemistry of [ 4278-08-4 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	11
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	43.98
TPSA :	28.68 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) :	-6.0 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.46
Log Po/w (XLOGP3) :	1.82
Log Po/w (WLOGP) :	2.64
Log Po/w (MLOGP) :	1.75
Log Po/w (SILICOS-IT) :	3.0
Consensus Log Po/w :	2.13

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.6
Solubility :	0.403 mg/ml ; 0.00249 mol/l
Class :	Soluble
Log S (Ali) :	-2.04
Solubility :	1.47 mg/ml ; 0.00908 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.02
Solubility :	0.0155 mg/ml ; 0.0000953 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.35

Safety of [ 4278-08-4 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H319	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 4278-08-4 ]

* 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 [ 4278-08-4 ]
Downstream synthetic route of [ 4278-08-4 ]

[ 4278-08-4 ] Synthesis Path-Upstream 1~2

1
[ 165901-26-8 ]
[ 4278-08-4 ]

Yield	Reaction Conditions	Operation in experiment
56.5%	With [bis(acetoxy)iodo]benzene; potassium carbonate In dimethyl sulfoxideDarkness	To a solution of 2-aryl-4,5- dihydro-lH-imidazole 14b, x (35 mmol) in DMSO (100 mL) was added potassium carbonate (38.5 mmol) and diacetoxyiodobenzene (38.5 mmol). The reaction mixture was stirred overnight in darkness. Water was added followed by extraction with dichloromethane. The organic layer was dried over magnesium sulfate and concentrated. The residue was subjected to flash column chromatography (hexane: ethyl acetate 3:2) to give a white solid. Yield: 30percent-50percent.
56.5%	With [bis(acetoxy)iodo]benzene; potassium carbonate In dimethyl sulfoxideDarkness	[002211 Method A (essential for only 9b, 9x, Figure 8): To a solution of 2-aryl-4,5- dihydro-1H-imidazole 14b, x (35 mmol) in DMSO (100 mL) was added potassium carbonate (38.5 mmol) and diacetoxyiodobenzene (38.5 mmol). The reaction mixture was stuffed overnight in darkness. Water was added followed by extraction with dichloromethane. The organic layer5 was dried over magnesium sulfate and concentrated. The residue was subjected to flash column chromatography (hexane: ethyl acetate 3:2) to give a white solid. Yield: 30percent-50percent.

Reference： [1] Journal of Medicinal Chemistry, 2010, vol. 53, # 20, p. 7414 - 7427
[2] Patent: WO2011/109059, 2011, A1, . Location in patent: Paragraph 0040; 00354
[3] Patent: WO2014/138279, 2014, A1, . Location in patent: Paragraph 00221; 00246
[4] Journal of the American Chemical Society, 2016, vol. 138, # 25, p. 7820 - 7823
[5] Heterocycles, 1995, vol. 40, # 2, p. 841 - 850

2
[ 459-57-4 ]
[ 4278-08-4 ]

Reference： [1] Patent: WO2014/138279, 2014, A1,
[2] Journal of the American Chemical Society, 2016, vol. 138, # 25, p. 7820 - 7823
[3] Patent: WO2011/109059, 2011, A1,

[ 4278-08-4 ] Synthesis Path-Downstream 1~48

1
[ 4278-08-4 ]
[ 72542-80-4 ]

Reference： [1]Journal of Heterocyclic Chemistry,1979,vol. 16,p. 1153 - 1155

2
[ 165901-26-8 ]
[ 4278-08-4 ]

Yield	Reaction Conditions	Operation in experiment
56.5%	With [bis(acetoxy)iodo]benzene; potassium carbonate; In dimethyl sulfoxide;Darkness;	To a solution of 2-aryl-4,5- dihydro-lH-imidazole 14b, x (35 mmol) in DMSO (100 mL) was added potassium carbonate (38.5 mmol) and diacetoxyiodobenzene (38.5 mmol). The reaction mixture was stirred overnight in darkness. Water was added followed by extraction with dichloromethane. The organic layer was dried over magnesium sulfate and concentrated. The residue was subjected to flash column chromatography (hexane: ethyl acetate 3:2) to give a white solid. Yield: 30%-50%.
56.5%	With [bis(acetoxy)iodo]benzene; potassium carbonate; In dimethyl sulfoxide;Darkness;	[002211 Method A (essential for only 9b, 9x, Figure 8): To a solution of 2-aryl-4,5- dihydro-1H-imidazole 14b, x (35 mmol) in DMSO (100 mL) was added potassium carbonate (38.5 mmol) and diacetoxyiodobenzene (38.5 mmol). The reaction mixture was stuffed overnight in darkness. Water was added followed by extraction with dichloromethane. The organic layer5 was dried over magnesium sulfate and concentrated. The residue was subjected to flash column chromatography (hexane: ethyl acetate 3:2) to give a white solid. Yield: 30%-50%.

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 7414 - 7427
[2]Patent: WO2011/109059,2011,A1 .Location in patent: Paragraph 0040; 00354
[3]Patent: WO2014/138279,2014,A1 .Location in patent: Paragraph 00221; 00246
[4]Journal of the American Chemical Society,2016,vol. 138,p. 7820 - 7823
[5]Heterocycles,1995,vol. 40,p. 841 - 850

4
7-[chloro(1-methyl-1H-imidazol-5-yl)methyl]-5-(3-chlorophenyl)tetrazolo[1,5-a]quinazoline monohydrochloride [ No CAS ]
[ 4278-08-4 ]
ClC₆H₄C₈H₃N₅CH(C₃H₂N₂)2CH₃C₆H₄F [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2007,vol. 42,p. 702 - 714

5
[ 98-09-9 ]
[ 4278-08-4 ]
[ 1253697-41-4 ]

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 7414 - 7427

6
[ 1313517-69-9 ]
[ 4278-08-4 ]
[ 1313519-13-9 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; at 140℃; for 1.0h;microwave irradiation; Inert atmosphere;	Intermediate CC (1 10 mg, 0.363 mmol), 2-(4-fluorophenyl)-lH-imidazole (70 mg, 0.435 mmol), Pd2(dba)3 CHCl3 (166 mg, 0.182 mmol), BINAP (226 mg, 0.3638 mmol), and CS2CO3 (354 mg, 1.08 mmol) were dissolved in 1 mL of toluene in a microwave vial and a stream of nitrogen was bubbled through the mixture for 2 minutes. The resulting solution was heated at 140 C for 1 h in a microwave. The reaction mixture was diluted with ethyl acetate and washed with saturated sodium bicarbonate solution. The organic extracts were dried with Na2S04, filtered and evaporated, and the residue was purified by preparative HPLC to give the title compound (48 mg). LCMS: 429.1 m/z (M+H)+; ret. Time 3.23 min (Analytical Method A).

Reference： [1]Patent: WO2011/79114,2011,A1 .Location in patent: Page/Page column 157

7
[ 1313518-05-6 ]
[ 4278-08-4 ]
[ 1313519-31-1 ]

Yield	Reaction Conditions	Operation in experiment
	In dimethyl sulfoxide; at 120℃; for 2.0h;	To a stirring mixture of Intermediate RR-1 (112 mg, 0.338 mmol) in 0.7 mL of DMSO, 2-(4-fluorophenyl)-lH-imidazole (109 mg, 0.67 mmol) was added. The reaction mixture was placed in a 120 C oil bath for 2 h. The crude mixture was directly loaded and purified by silica gel chromatography to give the coupled nitro ester. LCMS: 457.1 m/z (M+H)+. To a stirring mixture of the coupled nitro ester in 1.2 mL of MeOH, Pt/C (42 mg) was added and the reaction mixture was placed under 1 atm of hydrogen for 2 h. The hydrogen balloon was removed and VO(acac)2 (5 mg) was added. This reaction mixture was placed under 1 atm of hydrogen overnight. The crude mixture was filtered through a plug of Celite and the plug was washed several times with EtOAc. The filtrate was concentrated under reduced pressure. To this cyclized product, 0.5 mL of dioxane, potassium bicarbonate (100 mg) and trimethylphosphate (200 mg) were added. The reaction mixture was warmed to 100 C for several hours. The crude product mixture was cooled to rt and diluted with EtOAc and water. The layers were separated and the aqueous layer was extracted with EtOAc. The organic layers were dried over MgS04, filtered, and concentrated under reduced pressure. The resulting material was purified by preparative HPLC to give the title compound. LCMS: 409.1 m/z (M+H)+; ret. Time 4.07 min (Analytical MethodD).

Reference： [1]Patent: WO2011/79114,2011,A1 .Location in patent: Page/Page column 167

8
[ 1313518-05-6 ]
[ 4278-08-4 ]
[ 1313519-32-2 ]

Reference： [1]Patent: WO2011/79114,2011,A1

9
[ 1445-45-0 ]
[ 1313518-05-6 ]
[ 4278-08-4 ]
[ 1371625-19-2 ]

Yield	Reaction Conditions	Operation in experiment
		To a stirring mixture of Intermediate R -1 (0.338 mmol) in DMSO, 2-(4- fluorophenyl)-lH-imidazole (0.67 mmol) is added. The reaction mixture is placed in a 120 C oil bath for 2 h. The crude mixture is directly loaded and purified by silica gel chromatography to give the coupled nitro ester. To a stirring mixture of the coupled nitro ester in MeOH, Pt/C (42 mg) is added and the reaction mixture is placed under 1 atm of hydrogen for 2 h. The hydrogen balloon is removed and VO(acac)2 is added. This reaction mixture is placed under 1 atm of hydrogen overnight. The crude mixture is filtered through a plug of Celite and the plug is washed several times with EtOAc. The filtrate is concentrated under reduced pressure. This cyclized compound is then reacted similarly to the final step of Example 13 with either trimethyl ortho formate or trimethylorthoacetate to give the title compounds.

Reference： [1]Patent: WO2012/48129,2012,A2 .Location in patent: Page/Page column 368

10
[ 1313518-05-6 ]
[ 4278-08-4 ]
[ 149-73-5 ]
[ 1371625-18-1 ]

Yield	Reaction Conditions	Operation in experiment
		To a stirring mixture of Intermediate R -1 (0.338 mmol) in DMSO, 2-(4- fluorophenyl)-lH-imidazole (0.67 mmol) is added. The reaction mixture is placed in a 120 C oil bath for 2 h. The crude mixture is directly loaded and purified by silica gel chromatography to give the coupled nitro ester. To a stirring mixture of the coupled nitro ester in MeOH, Pt/C (42 mg) is added and the reaction mixture is placed under 1 atm of hydrogen for 2 h. The hydrogen balloon is removed and VO(acac)2 is added. This reaction mixture is placed under 1 atm of hydrogen overnight. The crude mixture is filtered through a plug of Celite and the plug is washed several times with EtOAc. The filtrate is concentrated under reduced pressure. This cyclized compound is then reacted similarly to the final step of Example 13 with either trimethyl ortho formate or trimethylorthoacetate to give the title compounds.

Reference： [1]Patent: WO2012/48129,2012,A2 .Location in patent: Page/Page column 368

11
[ 459-57-4 ]
[ 4278-08-4 ]

Reference： [1]Patent: WO2014/138279,2014,A1
[2]Journal of the American Chemical Society,2016,vol. 138,p. 7820 - 7823
[3]Patent: WO2011/109059,2011,A1

12
[ 1313517-71-3 ]
[ 4278-08-4 ]
[ 1313572-42-7 ]