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Chemical Structure| 16433-96-8

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Product Details of [ 16433-96-8 ]

CAS No. :16433-96-8
Formula : C8H5NO2
M.W : 147.13
SMILES Code : O=[N+](C1=CC=CC=C1C#C)[O-]
MDL No. :MFCD01113917
Boiling Point : No data available
InChI Key :FWAGYANFBMIHFQ-UHFFFAOYSA-N
Pubchem ID :1493957

Safety of [ 16433-96-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 16433-96-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 43.2
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

45.82 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.72
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

2.18
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

1.66
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

2.25
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

0.27
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.61

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-2.46
Solubility 0.506 mg/ml ; 0.00344 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-2.78
Solubility 0.247 mg/ml ; 0.00168 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-1.84
Solubility 2.13 mg/ml ; 0.0145 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

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)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

Yes
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-5.65 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

1.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

3.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

2.01

Application In Synthesis of [ 16433-96-8 ]

* 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.

  • Downstream synthetic route of [ 16433-96-8 ]

[ 16433-96-8 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 873-67-6 ]
  • [ 16433-96-8 ]
  • [ 92438-25-0 ]
YieldReaction ConditionsOperation in experiment
0.444 g With triethylamine; In chloroform; at 50℃; for 1.75h; General procedure: A solution of the oxime (3.10 mmol) and N-chlorosuccinimide (0.414 g, 3.10 mmol) im 4 mL anhydrous chloroform was treated with pyridine (0.014 mL, 0.17 mmol) and heated under nitrogen at 50 C for 1 h. Then acetylene 5 (0.400 g, 2.72 mmol) was added, followed by dropwise addition of triethylamine (0.52 mL, 3.8 mmol) over 15 min. The mixture was heated at 50 C for another 90 min, then cooled, treated with 60 mL water and extracted with dichloromethane (3 x 20 mL). The combined organic layers were dried over sodium sulfate and evaporated to dryness. The residue was purified by flash column chromatography using hexanes-ethyl acetate mixtures.
  • 2
  • [ 16433-96-8 ]
  • [ 52670-38-9 ]
YieldReaction ConditionsOperation in experiment
87.45% With palladium 10% on activated carbon; hydrazine hydrate; In ethanol;Heating; To a solution of compound 6k (1.5 g, 10.19 mmol) in ethanol(20 mL), 80% hydrazine monohydrate (1.8 g, 20.39 mmol) and 10%Pd/C (20 mg) were successively added. The reaction mixture was stirred under reflux at 80 C for 2-3 h and the reaction was monitored by TLC. After completion of the reaction, the solution was filtered to remove the Pd/C and the solvent was removed under vacuum. Then water and ethyl acetate were added to the residue and the organic layer was separated. The aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed in vacuo to give pure 2-ethynylaniline as light yellow oil liquid, yield: 87.45%. 3-ethynylaniline (7l) and 4-ethynylaniline (7m) were prepared withthe same method and the corresponding compounds 6l and 6m.
  • 3
  • [ 75867-47-9 ]
  • [ 16433-96-8 ]
YieldReaction ConditionsOperation in experiment
98% With potassium carbonate; In methanol; at 20℃; for 0.166667h; 38 g (173.27 mmol) of Intermediate E-1 was stirred with500 ml of methanol in a 1000 mE flask. 24 g (173.27 mmol) of potassium carbonate was added thereto, and the mixture was stirred for 10 minutes at room temperature to complete a reaction. The reactant was filtered, water and ethylacetatewere respectively added thereto in an amount of 500 ml after removing the potassium carbonate, and the water was separated through an extraction. The separated organic solvent was removed through a distiller to obtain Intermediate E-2(25.1 g, 98%).calcd. C8H5N02: C, 65.31; H, 3.43; N, 9.52; 0, 21.75; found: C, 65.25; H, 3.47; N, 9.56; 0, 21.58.
66% With tetrabutyl ammonium fluoride; In tetrahydrofuran; at -10 - 20℃; for 2h;Inert atmosphere; To a 3-neck RBF (2000 ml_) was added compound B (108g, 0.492mol), followed by the addition of THF(500 ml_). The mixture was cooled to -10 C under N2. The Bu4NF in THF was added dropwise below 0 C. After addition the reaction mixture was warmed to ambient temperature and stirred for two hours. TLC checked the reaction was completed. The reaction mixture was poured into water while keeping the temperature below 30 C, extracted with MTBE, washed with water, dried with sulfate sodium. After filtration the filtrate was concentrated on vacuum to give the crude product. Purification by Silica gel column chromatography gave the product (48g, yield: 66%).
62% With tetrabutyl ammonium fluoride; In tetrahydrofuran; at 20℃; for 1.5h;Inert atmosphere; Preparation of Compound 1-2 [105] After dissolving Compound 1-1 (39g, 178mmol) in THF (1.2L) at nitrogen atmosphere, tetrabutylammonium fluoride (280mL, 1M solution in THF, 213mmol) was added thereto. The reaction mixture was stirred at room temperature for 1.5 hours and extracted with distilled water and ethylacetate. After drying an organic layer with anhydrous MgSO4 and removing a solvent by a rotary type evaporator, Compound 1-2 (16.2g, 62%) was obtained via purification by column chromatography using methylene chloride (MC) and hexane as a developing solvent.
With methanol; potassium carbonate; In dichloromethane; at 20℃; for 5h; 8.022 g (36.6 mmol) of Intermediate (2) and 5.56 g (40.2 mmol) of K2CO3 were added to 20 mL of methanol and 80 mL of methylene chloride (DCM), and the resultant mixture was stirred at ambient temperature. After 5 hours, the completed reaction mixture was added to 300 mL of distilled H2O and an organic layer was extracted therefrom by using DCM. The extracted organic layer was dried by using MgSO4 and a solvent was removed therefrom by using an evaporator. A concentrated product was purified therefrom by silica gel column chromatography to obtain Intermediate (3).
2.07 g With methanol; potassium carbonate; at 20℃; for 0.166667h; General procedure: According to the reported method, 1 the title compound 1b was prepared from 1-bromo-4-chlorobenzene by the Sonogashira coupling and subsequent desilylation as follows. Under an argon atmosphere, TMSA (2.58 g, 26.2 mmol) was added to a stirred mixture of 1-bromo-4-chlorobenzene (3.83 g, 20.0 mmol), PdCl2(PPh3)2 (350 mg, 0.499 mmol) and CuI (95.2 mg, 0.500 mmol) in Et3N (40 mL). The mixture was heated to 80 C and stirred for 19 h. The resultant mixture was cooled to room temperature and passed through a short silica gel-activated carbon column. Evaporation of the filtrate under reduced pressure gave a light yellow solid (4.40 g). The crude product was dissolved in MeOH (40 mL) and treated with anhydrous K2CO3 (4.37 g, 31.6 mmol) at room temperature for 15h. The reaction mixture was quenched by dropwise addition of HCl (2 M in H2O, 10 mL) and extracted with CH2Cl2 (3 × 10 mL). The combined organic layer was washed with brine, dried overNa2SO4, and evaporated under reduced pressure. Purification of the residue by silica gel column chromatography (hexane) gave 1b as pale yellow solid (1.23 g, 9.22 mmol, 46%).

  • 5
  • [ 16433-96-8 ]
  • [ 609-73-4 ]
  • [ 25407-11-8 ]
YieldReaction ConditionsOperation in experiment
92% With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In ethanol; for 8h;Inert atmosphere; Reflux; To a RBF (1000 ml) was added compound C (25g, 0.17gmol), followed by the addition of Et3N (600 ml). The mixture was purged with N2 for 10 min. A catalyst amount of Pd (PPh3)2CI2 (200mg) and Cul (35mg) were added. The mixture was stirred for 6 hours, filtered and the solid was collected. The solid was reflux in ethanol (500ml_) for 2 hours and the solid was collected to give the crude product. The material was purified with crystallization from toluene to give the product (42g, 92%).
89% With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; at 20℃; Preparation of Compound 1-3 [107] After 2-iodonitrobenzene (22.4g, 130mmol), triethylamine (1.5L), Pd(PPh3)2Cl2 (3.7g, 5.4mmol), CuI (1g, 2.2mmol) and Compound 1-2 (16g, 109mmol) were mixed, the mixture was stirred at room temperature overnight. After dissolving suspension, which is obtained after filtration, in MC and performing silica filtering, Compound 1-3 (26g, 89%) was obtained via recrystallization with ethanol.
38% With pyrrolidine; copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); water; at 80℃; for 8h; General procedure: To a stirred mixture of 2-iodonitrobenzene (249 mg, 1.0 mmol), phenyl acetylene(153 mg, 1.5 mmol), pyrrolidine (142 mg, 2 mmol), Pd(PPh3)4 (12 mg,0.01 equiv) and CuI (2 mg, 1 mol %) were added followed by water (5 mL).The reaction mixture was then stirred at 80 C (oil bath temperature) for 8 h(TLC) and extracted with ethyl acetate (3 20 mL). The combined organicextract was washed with brine, dried over anhydrous Na2SO4, and evaporated to leave the crude product which was purified by column chromatography oversilica gel with hexane-ethyl acetate (90:10) as eluent to furnish pure 2-(2-nitrophenyl)-1-phenylethanone
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In tetrahydrofuran; at 50℃; for 3h;Inert atmosphere; 7.76 g (34.3 mmol) of 1-iodo-2-nitrobenzene (S), 5.05 g (34.3 mmol) of Intermediate (3), 1.20 g (1.72 mmol) of bis(triphenylphosphine)palladium(II)dichloride, and 0.65 g (3.43 mmol) of copper(I)iodide were dissolved in 60 mL of THF under an argon atmosphere. 10 mL of triethylamine was added thereto. Then, the resultant mixture was reacted at a temperature of 50 C. After 3 hours, a solvent was removed therefrom by using an evaporator. A concentrated product was purified therefrom by silica gel column chromatography to obtain Intermediate (4).

  • 6
  • [ 209259-55-2 ]
  • [ 16433-96-8 ]
  • 9
  • [ 16433-96-8 ]
  • [ 173043-61-3 ]
  • [ 473451-68-2 ]
  • 11
  • [ 16433-96-8 ]
  • [ 54-42-2 ]
  • C17H15N3O7 [ No CAS ]
  • 12
  • glycidyl azide polymer, Mn: 1344; monomer(s): epichlorohydrin [ No CAS ]
  • [ 16433-96-8 ]
  • glycidyl-4-(2'-nitrophenyl)-1,2,3-triazolyl polymer, Mn: 1798, PDI: 1.11; monomer(s): epichlorohydrin; 1-ethynyl-2-nitrobenzene [ No CAS ]
  • 16
  • [ 2295-12-7 ]
  • [ 16433-96-8 ]
  • [ 848785-51-3 ]
YieldReaction ConditionsOperation in experiment
bis-triphenylphosphine-palladium(II) chloride; In toluene; for 3h;Heating / reflux; 2-Nitro-phenylacetylene (prepared according to Synthesis 1980,627) (25g), 1, 1-dimethy-l-silacyclobutane (21. 9ML) and PDCL2 ( (PH3P) 2 (9. 5g) were refluxed in 450 ml dry toluiene under an atmosphere of nitrogen for 3 hours. After cooling to room temperature the solvent was evaporated and the residue (51.8g) was chromatographed over 1. 3kg of silica gel (eluent: hexane: ethylacetate: : 39: 1). An olive green oil (19.9g) was isolated, which contained (according to nrnr) 60% of Compound 28.83a. This material was used directly in the next step.
  • 17
  • [ 50-00-0 ]
  • [ 16433-96-8 ]
  • [ 108-18-9 ]
  • [ 1032008-59-5 ]
  • 18
  • [ 947513-67-9 ]
  • [ 16433-96-8 ]
  • [ 1008453-87-9 ]
  • 19
  • [ 54125-02-9 ]
  • [ 16433-96-8 ]
  • [ 20281-23-6 ]
  • 20
  • [ 16433-96-8 ]
  • [ 54781-19-0 ]
  • [ 20281-23-6 ]
  • 21
  • [ 16433-96-8 ]
  • [ 94930-52-6 ]
  • [ 1008453-83-5 ]
  • 22
  • [ 16433-96-8 ]
  • [ 1499-21-4 ]
  • C20H14NO3P [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% D. Substituted Biaryl Compounds using Non-Halogenated AlkynesWorking embodiments have used non-halogenated alkynes to produce phosphorus-containing compounds, as indicated below in Scheme 2.
  • 23
  • [ 1092543-15-1 ]
  • [ 16433-96-8 ]
  • 24
  • [ 1043552-64-2 ]
  • [ 16433-96-8 ]
  • [ 1043552-68-6 ]
  • 26
  • [ 16433-96-8 ]
  • [ 30810-15-2 ]
  • [ 1015-89-0 ]
  • 27
  • [ 16433-96-8 ]
  • [ 462660-31-7 ]
  • [ 1159414-18-2 ]
  • 28
  • [ 16433-96-8 ]
  • [ 1493-27-2 ]
  • [ 1160926-62-4 ]
  • 29
  • [ 90965-06-3 ]
  • [ 552-89-6 ]
  • [ 16433-96-8 ]
YieldReaction ConditionsOperation in experiment
82% With potassium carbonate; In methanol; for 8h; Weighed nitrobenzaldehyde (202mg, 1.33mmol) into a round bottom flask, in methanol (10mL); then weighed potassium carbonate (370mg, 2.6mmol, 2eq) into the mixture was added(306mg, 1.6mmol, 1.2 eq), after 8 hours the reaction was concentrated; was added H2O (15mL), ethyl acetate (40mL × 3) and extracted; the organic phase was washed with saturated NaHCO3 (40mL)H2O (40mL × 3), saturated sodium chloride solution (30 mL) and washed; and dried over anhydrous sodium sulfate suitable amount; concentrated and purified by column chromatography [the V (ethyl acetate) :V (petroleum ether) = 1:15 ] to give a white solid 160mg, 82% yield.
  • 30
  • [ 16433-96-8 ]
  • 2-(2-chloroethynyl)-1-nitrobenzene [ No CAS ]
  • 31
  • [ 862730-04-9 ]
  • [ 16433-96-8 ]
  • [ 1189793-21-2 ]
  • 32
  • [ 1184953-69-2 ]
  • [ 16433-96-8 ]
  • [ 1200070-75-2 ]
  • 33
  • [ 938-10-3 ]
  • [ 16433-96-8 ]
  • [ 1215090-07-5 ]
  • 34
  • [ 941-55-9 ]
  • [ 16433-96-8 ]
  • [ 1215090-01-9 ]
  • 35
  • [ 4547-64-2 ]
  • [ 16433-96-8 ]
  • [ 1215090-05-3 ]
 

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