Structure of 2-Amino-5-fluorophenol
CAS No.: 53981-24-1
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CAS No. : | 53981-24-1 |
Formula : | C6H6FNO |
M.W : | 127.12 |
SMILES Code : | C1=C(F)C=CC(=C1O)N |
MDL No. : | MFCD00671759 |
InChI Key : | IIDUNAVOCYMUFB-UHFFFAOYSA-N |
Pubchem ID : | 185763 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
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 ? Topological Polar Surface Area: Calculated from |
46.25 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.03 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.07 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.54 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.24 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.09 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.19 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.8 |
Solubility | 2.04 mg/ml ; 0.016 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.63 |
Solubility | 2.96 mg/ml ; 0.0233 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.7 |
Solubility | 2.52 mg/ml ; 0.0199 mol/l |
Class? Solubility class: Log S scale |
Soluble |
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) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
Yes |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.32 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
2.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.0 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With tetra-N-butylammonium tribromide; potassium carbonate; In acetonitrile;Reflux; | 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, 87%). 1H NMR (DMSO-d6, 400 MHz): delta10.71 (s, 1H), 6.84-6.88 (m, 2H), 6.76-6.81 (m, 1H), 4.57 (s, 2H). |
76.05% | With tetrabutylammomium bromide; potassium carbonate; In acetonitrile; at 65℃; for 15h;Inert atmosphere; | To 2-amino-5-fluorophenol (500mg, 3.94mmol)Acetonitrile (5mL)Chloroacetyl chloride (490mg, 4.33mmol),Potassium carbonate (1.63g, 11.82mmol)And tetrabutylammonium bromide (126 mg, 0.39 mmol).The reaction mixture was heated to 65 C under a nitrogen atmosphere for 15 hours.Cool to room temperature, suction filter, and concentrate the filtrate in vacuo.Purification by column chromatography gave the compound as a yellow oil (500 mg, yield: 76.05%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 6h; | A suspension of 2-amino-5-fluorophenol (5.0 g, 39.37 mmol), 1,2-dibromoethane (21.9 g, 118.15 mmol), and potassium carbonate (27.16 g, 196.8 mmol) in DMF (50 mL) was stirred at 100C for 6 h. The reaction was diluted with water and extracted the product into ethyl acetate. The combined organic layer was washed with water, brine, dried over anhyd. Na2S04 and concentrated in vacuo. The residue was purified by column chromatography over silica gel (100-200 mesh) with 10% ethyl acetate in pet-ether as eluant gave 2.6 g (43%) of 7-fluoro-3,4- dihydro-2H-benzo[b][1,4]oxazine I-73 as a brown solid. 1H NMR (400 MHz, CDCI3): 6.46-6.55 (m, 3H), 4.24 (t, J = 4.4 Hz, 2H), 3.61 (br. s, 1H), 3.38 (t, J = 4.4 Hz, 2H). |
With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 125℃; | To a solution of 5-fluoro-2-nitrophenol (9.50 g) in methanol (10 ml), 5% palladium on activated carbon (1.90 g) was added and stirred overnight under a hydrogen atmosphere at room temperature. The catalyst was filtered off and the solvent was distilled off under reduced pressure. The resulting residue was converted into a powder form by addition of chloroform, and then collected by filtration to give 2-amino-5-fluorophenol (6.81 g) as a brown powder. To a solution of 2-amino-5-fluorophenol thus obtained (3.00 g) in N,N-dimethylformamide (20 ml), potassium carbonate (16.31 g) and 1,2-dibromoethane (3.05 ml) were added and stirred at 125C for 10 hours. The reaction mixture was allowed to stand overnight at room temperature, to which additional 1,2-dibromoethane (1.52 ml) was then added and stirred at 125C for 7 hours. After cooling at room temperature, the reaction mixture was diluted with water under ice cooling and extracted with ethyl acetate. The organic layer was washed sequentially with water and brine, dried over anhydrous sodium sulfate and then filtered to remove the desiccant, followed by distilling off the solvent under reduced pressure. The resulting residue was purified by NH silica gel column chromatography (eluting solvent: n-hexane:ethyl acetate = 9:1 to 7:3) to give the titled compound, i.e., 7-fluoro-3,4-dihydro-2H-1,4-benzoxazine (1.15 g) as a red-brown oil. 1H NMR (300 MHz, CHLOROFORM-D) δ 3.35-3.42 (m, 2 H), 3.60 (brs, 1 H), 4.22-4.26 (m, 2 H), 6.44-6.56 (m, 3 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
12% | 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, 0-50% ethyl acetate- dichloromethane, 60 min). Pure fractions were combined and evaporated to give the title compound (96 mg, 12%). LCMS RT=1.97 min, ES+ve m/z 164 (M+H)+. RT=2.85 min, ES+ve m/z 176 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With hydrogenchloride; In water; at 111℃; for 24.0h; | 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 15% ethyl acetate/cyclohexane with methanol) to give the desired quinoline product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium fluoride; potassium carbonate; In N,N-dimethyl-formamide; at 50 - 80℃; | A certain amount of DMF, potassium carbonate, and C6H6FNO and potassium fluoride obtained in step (1) were sequentially added to the reactor.KF, a certain amount of methyl chloroacetate was added dropwise, and the dropping was controlled for 2 to 3 hours without significant exotherm.After the completion of the addition of 50-80 C reaction for 4 hours, the mixture gradually turned yellow, sampling raw materials less than 0.5%;After passing the filter to remove the potassium salt,Filtrate recovery DMF,After recycling, add a certain amount of methanol, warm up to 60-70 degrees, heat for 30 minutes, and start cooling down to 10-20 degrees.Filter to give Intermediate 2; |
Tags: 53981-24-1 synthesis path| 53981-24-1 SDS| 53981-24-1 COA| 53981-24-1 purity| 53981-24-1 application| 53981-24-1 NMR| 53981-24-1 COA| 53981-24-1 structure
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