Home Cart 0 Sign in  

[ CAS No. 53981-24-1 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
Chemical Structure| 53981-24-1
Chemical Structure| 53981-24-1
Structure of 53981-24-1 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 53981-24-1 ]

Related Doc. of [ 53981-24-1 ]

Alternatived Products of [ 53981-24-1 ]

Product Details of [ 53981-24-1 ]

CAS No. :53981-24-1 MDL No. :MFCD00671759
Formula : C6H6FNO Boiling Point : -
Linear Structure Formula :- InChI Key :IIDUNAVOCYMUFB-UHFFFAOYSA-N
M.W : 127.12 Pubchem ID :185763
Synonyms :

Calculated chemistry of [ 53981-24-1 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 9
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.0
Num. rotatable bonds : 0
Num. H-bond acceptors : 2.0
Num. H-bond donors : 2.0
Molar Refractivity : 32.83
TPSA : 46.25 Ų

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 : Yes
Log Kp (skin permeation) : -6.32 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.03
Log Po/w (XLOGP3) : 1.07
Log Po/w (WLOGP) : 1.54
Log Po/w (MLOGP) : 1.24
Log Po/w (SILICOS-IT) : 1.09
Consensus Log Po/w : 1.19

Druglikeness

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

Water Solubility

Log S (ESOL) : -1.8
Solubility : 2.04 mg/ml ; 0.016 mol/l
Class : Very soluble
Log S (Ali) : -1.63
Solubility : 2.96 mg/ml ; 0.0233 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -1.7
Solubility : 2.52 mg/ml ; 0.0199 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 2.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.0

Safety of [ 53981-24-1 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H332-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 53981-24-1 ]

* 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 [ 53981-24-1 ]
  • Downstream synthetic route of [ 53981-24-1 ]

[ 53981-24-1 ] Synthesis Path-Upstream   1~12

  • 1
  • [ 127682-43-3 ]
  • [ 372-20-3 ]
  • [ 399-95-1 ]
  • [ 53981-24-1 ]
  • [ 53981-23-0 ]
Reference: [1] Journal of the American Chemical Society, 1992, vol. 114, # 25, p. 9795 - 9806
  • 2
  • [ 446-36-6 ]
  • [ 53981-24-1 ]
YieldReaction ConditionsOperation in experiment
94% With hydrogen In ethanol for 1.5 h; Intermediate 13
2-Amino-5-fluorophenol
A solution of 5-fluoro-2-nitrophenol (commercially available, for example, from Aldrich) (2.50 g, 15.9 mmol) in ethanol (50 ml) was hydrogenated over 10percent palladium on carbon (980 mg) for 1.5 h. The catalyst was removed by filtration and the filtrate was concentrated. The solid residue was taken up in ether and an equal volume of cyclohexane was added. Removal of ether in vac at room temperature afforded a pale grey solid which was filtered and washed with cyclohexane (1.90 g, 94percent). Found: C, 56.4; H, 4.8; N, 10.9. C6H6FNO requires C, 56.7; H, 4.8; N, 1 1.0percent.
93% With hydrogen In ethanol a.
2-amino-5-fluorophenol
To 500 mg of 10percent palladium on carbon in a Parr bottle with 50 ml of anhydrous ethanol was added a solution of 10 g (64 mmol) 5-fluoro-2-nitrophenol in 150 ml ethanol.
The flask was evacuated, charged with hydrogen and shaken on a Parr apparatus for 1 hour.
The catalyst was removed by filtration through Celite.(R). and the filtrate was evaporated to dryness in vacuo to give 7.54 g (93percent yield) of a dark solid shown to be the desired product by 1 H NMR.
93% With hydrogen In ethanol a.
2-amino-5-fluorophenol
To 500 mg of 10percent palladium on carbon in a Parr bottle containing 50 ml of anhydrous ethanol was added a solution of 10 g (64 mmol) 5-fluoro-2-nitrophenol in 150 ml ethanol.
The flask was evacuated, charged with hydrogen and shaken on a Parr apparatus for 1 hour.
The catalyst was removed by filtration through.
Celite.(R). and the filtrate was evaporated to dryness in vacuo to give 7.54 g (93percent yield) of a dark solid.
82% With 10% palladium on activated carbon; Degussa type; hydrogen In methanol for 3 h; To a of solution of 5-fluoro-2-nitrophenol (6.37 mmol, 1.00 g) in methanol (100 mL), 10percent palladium on activated carbon (10 wtpercent of 5-fluoro-2-nitrophenol, 0.10 g) was added. The reaction was flushed with argon followed by hydrogen for fifteen minutes each with constant magnetic stirring. The reaction was then maintained under hydrogen atmosphere at ordinary pressure (15 psi) for three hours. Argon was again flushed through the reaction vessel for 15 minutes. Then the reaction contents were filtered over a thin pad of celite which was then washed with methanol (70 mL). The filtrate was concentrated in vacuo yielding a brown solid. Silica gel column chromatography (10:1 hexanes/chlorofrom) provided a crystalline orange solid in an 82percent yield.
44%
Stage #1: at 20℃;
Stage #2: With sodium hydrogencarbonate In dichloromethane; water
Example 62; 6-Fluoro-2-(4-(pyddin-2-yl)but-3-3Dyl)benzordloxazole ;62 (A) ;2-Amino-5-fluorophenol; A suspension of 3-fluoro-6-nitrophenol (500 mg, 3.18 mmol) and zinc (2.10 g, 31.8 mmol) in acetic acid (7.3 mL) was stirred overnight at room temperature. The reaction mixture was filtered through celite and washed with DCM. After evaporation and distillation under vacuum (2.10-2 mbar) of the solvents, the residue was dissolved in DCM. The organic phase was washed with a saturated solution of NaHC03 and brine, dried over MgS04, filtered and evaporated. The crude residue was purified by flash chromatography (DCM/MeOH 99.5: 0.5) to yield 177 mg (1.39 mmol, 44percent) of 2- amino-5-fluorophenol as an orange solid.
21.6 g With 10% palladium on activated carbon; Degussa type; hydrogen In ethanol at 20℃; Inert atmosphere To 5-fluoro-2-nitrophenol (26.63 g, 170 mmol) in Ethanol (250 ml) under N2 atmosphere was added palladium on carbon (10 wt percent, 250 mg, 0.235 mmol). The mixture was flushed with H2 and stirred at RT under H2 (balloon) until complete conversion according to thin layer chromatography (TLC) analysis. Pd/C was removed by filtration and the filtrate was concentrated to yield 21.6 g of the title compound. [0535] 1H NMR (DMSO): 4.5 (br, 2H); 6.35 (dd, 1H); 6.45 (dd, 1H); 6.50 (dd, 1H); 9.5 (br, 1H).

Reference: [1] Journal of Medicinal Chemistry, 2015, vol. 58, # 24, p. 9742 - 9753
[2] Patent: WO2010/94643, 2010, A1, . Location in patent: Page/Page column 46
[3] Patent: US5238908, 1993, A,
[4] Patent: US5393735, 1995, A,
[5] Chemistry - A European Journal, 2011, vol. 17, # 33, p. 9076 - 9082
[6] Patent: WO2005/85202, 2005, A1, . Location in patent: Page/Page column 53
[7] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 15, p. 3521 - 3525
[8] Advanced Synthesis and Catalysis, 2010, vol. 352, # 11-12, p. 1834 - 1840
[9] Patent: US5886044, 1999, A,
[10] Patent: US5780483, 1998, A,
[11] Patent: US6262113, 2001, B1,
[12] Patent: WO2005/123703, 2005, A2, . Location in patent: Page/Page column 121-122
[13] Collection of Czechoslovak Chemical Communications, 1994, vol. 59, # 9, p. 2119 - 2122
[14] Patent: US6136831, 2000, A,
[15] Patent: EP2172453, 2010, A1, . Location in patent: Page/Page column 14-15
[16] Patent: WO2010/145992, 2010, A1, . Location in patent: Page/Page column 87; 88
[17] Patent: WO2011/57935, 2011, A1, . Location in patent: Page/Page column 67
[18] Patent: WO2012/41789, 2012, A1, . Location in patent: Page/Page column 77
[19] Patent: WO2012/80239, 2012, A1, . Location in patent: Page/Page column 69
[20] Patent: US2013/267417, 2013, A1, . Location in patent: Paragraph 0533-0535
[21] Journal of Materials Chemistry A, 2017, vol. 5, # 22, p. 10986 - 10997
[22] Archiv der Pharmazie, 2018, vol. 351, # 5,
  • 3
  • [ 367-25-9 ]
  • [ 53981-24-1 ]
Reference: [1] Patent: CN107459495, 2017, A, . Location in patent: Paragraph 0036; 0037; 0044; 0045
  • 4
  • [ 127682-43-3 ]
  • [ 372-20-3 ]
  • [ 399-95-1 ]
  • [ 53981-24-1 ]
  • [ 53981-23-0 ]
Reference: [1] Journal of the American Chemical Society, 1992, vol. 114, # 25, p. 9795 - 9806
  • 5
  • [ 127682-43-3 ]
  • [ 372-20-3 ]
  • [ 399-95-1 ]
  • [ 53981-24-1 ]
  • [ 53981-23-0 ]
Reference: [1] Journal of the American Chemical Society, 1992, vol. 114, # 25, p. 9795 - 9806
  • 6
  • [ 3054-95-3 ]
  • [ 53981-24-1 ]
  • [ 135838-04-9 ]
YieldReaction ConditionsOperation in experiment
55% With hydrogenchloride In water at 111℃; for 24 h; General procedure: A 1N HCl solution (82.5 mL) was added to the aniline (~1 mmol) in a round bottom flask. To this was added acrolein diethyl acetal (2.5 mmol). The resulting solution was refluxed at 111 °C for 24 hours. After cooling to room temperature, the solution was neutralized (pH 7−8) by addition of solid Na2CO3. The product was then extracted into dichloromethane (3 x 100 mL), and the combined organic layers were dried over Na2SO4 and evaporated under reduced pressure. The crude residue was then purified by column chromatography (elution mixture of hexane with ethyl acetate or 15percent ethyl acetate/cyclohexane with methanol) to give the desired quinoline product.
Reference: [1] Tetrahedron Letters, 2015, vol. 56, # 46, p. 6436 - 6439
  • 7
  • [ 53981-24-1 ]
  • [ 107-02-8 ]
  • [ 135838-04-9 ]
YieldReaction ConditionsOperation in experiment
12%
Stage #1: With hydrogenchloride In water; toluene at 100℃;
Stage #2: With sodium hydroxide In water
Intermediate 14
6-Fluoro-8-q uinolinol
2-Amino-5-fluorophenol (for example, as prepared for Intermediate 13) (602 mg, 4.74 mmol) was dissolved in 5M hydrochloric acid (21 ml). Toluene (6.5 ml) and acrolein (1 ml, 14 mmol) were added to the solution and the mixture was stirred at 1000C overnight. The aqueous layer was removed and 10M sodium hydroxide was added until the solution was neutral. The compound which precipitated was extracted with dichloromethane and the organic phase was washed with water and brine, then it was dried with sodium sulphate, filtered and evaporated. The residue was dissolved in dichloromethane and purified by Flashmaster (50 g cartridge, 0-50percent ethyl acetate- dichloromethane, 60 min). Pure fractions were combined and evaporated to give the title compound (96 mg, 12percent). LCMS RT=1.97 min, ES+ve m/z 164 (M+H)+. RT=2.85 min, ES+ve m/z 176 (M+H)+.
Reference: [1] Chemical Communications, 2015, vol. 51, # 84, p. 15458 - 15461
[2] Patent: WO2010/94643, 2010, A1, . Location in patent: Page/Page column 46
  • 8
  • [ 53981-24-1 ]
  • [ 56-81-5 ]
  • [ 135838-04-9 ]
Reference: [1] Monatshefte fur Chemie, 2002, vol. 133, # 11, p. 1437 - 1442
  • 9
  • [ 53981-24-1 ]
  • [ 153403-53-3 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 16, p. 4689 - 4693
[2] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 7, p. 1975 - 1980
[3] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 9, p. 3044 - 3049
[4] Patent: WO2014/164749, 2014, A1,
  • 10
  • [ 53981-24-1 ]
  • [ 79-04-9 ]
  • [ 103361-99-5 ]
YieldReaction ConditionsOperation in experiment
87% With tetra-N-butylammonium tribromide; potassium carbonate In acetonitrileReflux To a suspension of 2-amino-5-fluorophenol (Alfa, 15.00 g, 118 mmol), K2CO3 (48.9 g, 354 mmol) and tetrabutyl-ammonium bromide (3.80 g, 11.80 mmol) in MeCN (200 mL) was added 2-chloroacetyl chloride (14.66 g, 130 mmol) dropwise at 0° C. The reaction mixture was warmed to rt and then heated at reflux overnight. The reaction mixture was cooled to ambient temperature and concentrated in vacuo. The solid was collected, washed with water (100 mL) and dried in vacuo to give 7-fluoro-4H-benzo[1,4]oxazin-3-one as a pale solid (17.2 g, 87percent). 1H NMR (DMSO-d6, 400 MHz): δ10.71 (s, 1H), 6.84-6.88 (m, 2H), 6.76-6.81 (m, 1H), 4.57 (s, 2H).
Reference: [1] Archiv der Pharmazie, 2018, vol. 351, # 5,
[2] Patent: US2014/206663, 2014, A1, . Location in patent: Paragraph 0977; 0978
[3] Journal of Medicinal Chemistry, 2015, vol. 58, # 1, p. 222 - 236
[4] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 16, p. 4700 - 4704
  • 11
  • [ 53981-24-1 ]
  • [ 96-34-4 ]
  • [ 103361-99-5 ]
Reference: [1] Patent: CN107459495, 2017, A, . Location in patent: Paragraph 0036; 0038; 0048; 0049
  • 12
  • [ 53981-24-1 ]
  • [ 103361-99-5 ]
Reference: [1] Patent: WO2014/78802, 2014, A1,
Recommend Products
Same Skeleton Products
Historical Records

Related Functional Groups of
[ 53981-24-1 ]

Fluorinated Building Blocks

Chemical Structure| 399-97-3

[ 399-97-3 ]

2-Amino-4-fluorophenol

Similarity: 0.96

Chemical Structure| 53981-23-0

[ 53981-23-0 ]

2-Amino-3-fluorophenol

Similarity: 0.92

Chemical Structure| 450-91-9

[ 450-91-9 ]

4-Fluoro-2-methoxyaniline

Similarity: 0.90

Chemical Structure| 53981-25-2

[ 53981-25-2 ]

6-Fluoro-2-aminophenol

Similarity: 0.90

Chemical Structure| 399-95-1

[ 399-95-1 ]

4-Amino-3-fluorophenol

Similarity: 0.89

Aryls

Chemical Structure| 399-97-3

[ 399-97-3 ]

2-Amino-4-fluorophenol

Similarity: 0.96

Chemical Structure| 53981-23-0

[ 53981-23-0 ]

2-Amino-3-fluorophenol

Similarity: 0.92

Chemical Structure| 450-91-9

[ 450-91-9 ]

4-Fluoro-2-methoxyaniline

Similarity: 0.90

Chemical Structure| 53981-25-2

[ 53981-25-2 ]

6-Fluoro-2-aminophenol

Similarity: 0.90

Chemical Structure| 399-95-1

[ 399-95-1 ]

4-Amino-3-fluorophenol

Similarity: 0.89

Amines

Chemical Structure| 399-97-3

[ 399-97-3 ]

2-Amino-4-fluorophenol

Similarity: 0.96

Chemical Structure| 53981-23-0

[ 53981-23-0 ]

2-Amino-3-fluorophenol

Similarity: 0.92

Chemical Structure| 450-91-9

[ 450-91-9 ]

4-Fluoro-2-methoxyaniline

Similarity: 0.90

Chemical Structure| 53981-25-2

[ 53981-25-2 ]

6-Fluoro-2-aminophenol

Similarity: 0.90

Chemical Structure| 399-95-1

[ 399-95-1 ]

4-Amino-3-fluorophenol

Similarity: 0.89