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Structure of 14678-05-8

Chemical Structure| 14678-05-8

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Product Details of [ 14678-05-8 ]

CAS No. :14678-05-8
Formula : C3H4N2O
M.W : 84.08
SMILES Code : NC1=CC=NO1
MDL No. :MFCD00128192
InChI Key :IAXWZYXUKABJAN-UHFFFAOYSA-N
Pubchem ID :84591

Safety of [ 14678-05-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 14678-05-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 6
Num. arom. heavy atoms 5
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 20.91
TPSA ?

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

52.05 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.85
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

0.02
Log Po/w (WLOGP)?

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

0.26
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.

-0.72
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

0.42
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.17

Water Solubility

Log S (ESOL):?

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

-0.99
Solubility 8.59 mg/ml ; 0.102 mol/l
Class?

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

Very soluble
Log S (Ali)?

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

-0.67
Solubility 18.2 mg/ml ; 0.216 mol/l
Class?

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

Very 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

-0.77
Solubility 14.3 mg/ml ; 0.17 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

No
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

No
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.

-6.8 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

2.0
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

0.0 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)

2.21

Application In Synthesis of [ 14678-05-8 ]

* 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 [ 14678-05-8 ]

[ 14678-05-8 ] Synthesis Path-Downstream   1~17

  • 1
  • [ 7341-96-0 ]
  • [ 14678-05-8 ]
  • 2
  • [ 24683-26-9 ]
  • [ 14678-05-8 ]
  • [ 79672-22-3 ]
  • 4
  • 3-(trimethylsilyloximino)propionitrile [ No CAS ]
  • [ 14678-05-8 ]
  • 5
  • [ 96568-04-6 ]
  • [ 122-51-0 ]
  • [ 14678-05-8 ]
  • (Z)-2-(2,6-Dichloro-5-fluoro-pyridine-3-carbonyl)-3-(isoxazol-5-ylamino)-acrylic acid ethyl ester [ No CAS ]
  • 6
  • [ 60838-50-8 ]
  • [ 7803-49-8 ]
  • [ 14678-05-8 ]
YieldReaction ConditionsOperation in experiment
In water; at 80℃; for 3.0h; The 5-aminoisoxazole used as starting material was prepared as follows:- EPO <DP n="53"/>A 50% w/w solution of hydroxylaminbeta in water (6.6 m) and3-methoxyacrylonitrile (8.39 ml) were heated at 8O0C for 3 hours. The reaction mixture was cooled to room temperature and extracted with diethyl ether. The combined organic layers were washed with brine, dried (magnesium sulphate) and concentrated to a brown oil which solidifed on standing to give the title compound (3.87 g); NMR Spectrum: (DMSOd6) 4.88 (d, IH), 6.60 (s, 2H), 7.97 (d, IH); Mass Spectrum: M+ 83.
  • 7
  • C21H21ClN4O2 [ No CAS ]
  • [ 14678-05-8 ]
  • N-isoxazol-5-yl-4-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
In pyridine; for 18.0h; To a stirred slurry of 4-methyl-3-[6-(4-methylpiperazin-l-yl)-4-oxoquinazolin- 3(4H)-yl]benzoic acid (0.3 g) and DMF (0.05 ml) in methylene chloride (30 ml) at 350C was added thionyl chloride (0.3 ml). The resultant yellow solution was stirred at 45C for 1.5 hours. The reaction mixture was concentrated to give a yellow / orange solid. The solid was stirred in methylene chloride (30 ml) at room temperature with <strong>[14678-05-8]5-aminoisoxazole</strong> (0.11 g) and pyridine (0.2 ml) for 18 hours. The reaction mixture was washed with saturated NaHCO3 solution, brine and concentrated. The residue was purified by column chromatography on a silica column using initially methylene chloride and then a 9:1 mixture of methylene chloride and methanol as eluent. There was thus obtained the title compound (70 mg); NMR Spectrum: (DMSOd6) 2.19 (s, 3H), 2.25 (s, 3H), 2.49 (m, 4H), 3.30 (m, 4H), 6.43 (d, IH), 7.50 (d, IH), 7.62 (s, IH), 7.65 (m, 2H)3 8.08 (s, IH), 8.10 (m, IH), 8.13 (s, IH), 8.50 (d, IH), 12.04 (s, IH); Mass Spectrum: MH-H+ 444.
  • 8
  • [ 98349-24-7 ]
  • [ 122-51-0 ]
  • [ 14678-05-8 ]
  • ethyl 2-(2,4,5-trifluorobenzoyl)-3-(isoxazol-5-ylamino)acrylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With acetic anhydride; In methanol; chloroform; Example 37 Synthesis of ethyl 2-(2,4,5-trifluorobenzoyl)-3-(isoxazol-5-ylamino)acrylate (Compound No. 87) Ethyl 2,4,5-trifluorobenzoylacetate (1.50 g), 1.36 g of ethyl orthoformate and 2.80 g of acetic anhydride were combined, followed by heating at 130C for 3 hours. Excess ethyl orthoformate and acetic anhydride were distilled off. The residue was dissolved in 30 ml of chloroform. To the resulting solution, a solution of 512 mg of <strong>[14678-05-8]5-aminoisoxazole</strong> in 30 ml of methanol was added, followed by stirring at room temperature for 3 hours. The solvent was distilled off. The residue was purified using a silica gel column (hexane:chloroform = 1:1), whereby 1.74 g of the title compound was obtained as a colorless solid.
  • 9
  • [ 14678-05-8 ]
  • [ 17341-93-4 ]
  • [ 887624-84-2 ]
YieldReaction ConditionsOperation in experiment
53.9% With pyridine; In tetrahydrofuran; at 0℃; for 1.16667h; (4) 2,2,2-Trichloroethyl isoxazol-5-ylcarbamate; To a solution of <strong>[14678-05-8]isoxazole-5-amine</strong> (740 mg, 8.80 mmol) and pyridine (2.14 ml, 26.4 mmol) in tetrahydrofuran (10 ml) was added 2,2,2-trichloroethyl chloroformate (1.82 ml, 13.2 mmol) with ice-cooling and the mixture was stirred for 40 minutes with ice-cooling. To the mixture was further added 2,2,2-trichloroethyl chloroformate (1.82 ml, 13.2 mmol) with ice-cooling and the mixture was stirred for 30 minutes with ice-cooling, the reaction mixture was poured into ice-water and the mixture was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane : ethyl acetate = 1 : 1) to obtain the desired product (1.23 g, 53.9%) as a solid. 1H-NMR (CDCl3) delta; 4.87 (2H, s), 6.20 (1H, d, J = 2.1 Hz), 8.00 (1H, br s), 8.18 (1H, d, J = 2.1 Hz).
  • 10
  • [ 1070-71-9 ]
  • [ 14678-05-8 ]
YieldReaction ConditionsOperation in experiment
29.9% With sodium hydroxide; hydroxylamine hydrochloride; In methanol; water; at 30℃; for 12.0h; (3) Isoxazole-5-amine; A mixture of propiolonitrile (1.54 g, 30.2 mmol), hydroxylamine hydrochloride (2.10 g, 30.2 mmol), an aqueous 10% sodium hydroxide solution (12.1 ml, 30.2 mmol) and methanol (12 ml) was stirred at 30C for 12 hours. The reaction mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate) to obtain the desired product (760 mg, 29.9%) as a solid. 1H-NMR (CDCl3) delta; 4.51 (2H, br s), 5.11 (2H, d, J = 2.1 Hz), 7.96 (2H, d, J = 2.1 Hz).
  • 11
  • [ 14678-05-8 ]
  • [ 348111-64-8 ]
  • [ 501921-81-9 ]
  • 12
  • (2E)-2-[(3-methyl-1H-indazol-5-yl)methylidene]-3-oxobutan-1-nitrile [ No CAS ]
  • [ 14678-05-8 ]
  • [ 1261289-71-7 ]
YieldReaction ConditionsOperation in experiment
69% In isopropyl alcohol;Reflux; Example 26-Methyl-4-(3-methyl-lH-indazol-5-yl)-4,7-dihydroisoxazolo[5,4-b]pyridine-5-carbonitrileA mixture of 50 mg (0.22 mmol) (2£)-2-[(3-methyl-lH-indazol-5-yl)methylidene]-3-oxobutane- nitrile (Example 2A) and 19 mg (0.22 mmol) 1 ,2-oxazol-5-amine in propan-2-ol (1.0 ml) was stirred at reflux temperature overnight. The reaction mixture was then concentrated under reduced pressure, and the residue was purified by preparative RP-EtaPLC (acetonitrile/water + 0.1% TFA gradient) to yield 45 mg (69% of th.) of the racemic title compound.LC-MS (method 2): R, = 0.85 min; MS (ESIpos): m/z = 292 (M+Eta)+ 1H-NMR (400 MHz, DMSOd6): delta = 12.63 (br. s, IH), 10.91 (s, IH), 8.14 (s, IH), 7.55 (s, IH), 7.43 (d, IH), 7.19 (d, IH), 5.02 (s, IH), 2.48 (s, 3H), 2.16 (s, 3H) ppm.
  • 13
  • [ 14678-05-8 ]
  • [ 10397-30-5 ]
  • C11H9N3O4 [ No CAS ]
  • 14
  • [ 1450923-35-9 ]
  • [ 14678-05-8 ]
  • [ 1450920-98-5 ]
YieldReaction ConditionsOperation in experiment
25.2 mg With lithium hexamethyldisilazane; In tetrahydrofuran; for 0.916667h;Cooling with acetone-dry ice; A round bottom flask was charged with perfluorophenyl 4-(2-cyano-4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonate (44.1 mg, 0.080 mmol), <strong>[14678-05-8]isoxazol-5-amine</strong> (10.1 mg, 0.12 mmol, Matrix Scientific, Columbia, SC) and THF (1 mL) to give a a clear, colorless solution. The flask was cooled in a dry ice-acetone bath for 5 min, then lithium bis(trimethylsilyl)amide (1M in THF) (168 mu, 0.168 mmol) was added dropwise over 30 s to give a light-yellow solution. After 10 min, the flask was lowered into an ice bath for 45 min. Glacial acetic acid (1 drop) was added, and the mixture was concentrated under a vacuum. The product was purified by chromatography on silica gel (12g column with 0 to 10% MeOH/DCM) to give 4-(2-cyano-4-(trifluoromethyl)phenyl)-N-(isoxazol-5-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (25.2 mg, 0.056 mmol) as a light-yellow solid. 1H NMR (400MHz, DMSO-d6) delta ppm 12.18 (br. s., 1 H), 8.42 (d, J= 2.1 Hz, 1 H), 8.34 (d, J= 2.0 Hz, 1 H), 8.11 (dd, J= 2.0, 8.9 Hz, 1 H), 7.76 (d, J= 8.6 Hz, 1 H), 7.30 (d, J= 2.2 Hz, 1 H), 7.23 (dd, J= 2.2, 8.7 Hz, 1 H), 6.80 (d, J= 8.6 Hz, 1 H), 5.77 (d, J= 1.9 Hz, 1 H), 4.40 - 4.35 (m, 2 H), 3.89 - 3.86 (m, 2 H). m/z (ESI) 451.4 (M+H)+.
25 mg With lithium hexamethyldisilazane; In tetrahydrofuran; for 0.916667h;Cooling with acetone-dry ice; A round bottom flask was charged with perfluorophenyl 4-(2-cyano-4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonate (44 mg, 0.080 mmol), <strong>[14678-05-8]isoxazol-5-amine</strong> (10 mg, 0.12 mmol, Matrix Scientific, Columbia, SC) and THF (1 mL) to give a a clear, colorless solution. The flask was cooled in a dry ice-acetone bath for 5 min, then lithium bis(trimethylsilyl)amide (1M in THF) (170 mul, 0.170 mmol) was added dropwise over 30 s to give a light-yellow solution. After 10 min, the flask was lowered into an ice bath for 45 min. Glacial acetic acid (1 drop) was added, and the mixture was concentrated under a vacuum. The product was purified by chromatography on silica gel (12g column with 0 to 10% MeOH/DCM) to give 4-(2-cyano-4-(trifluoromethyl)phenyl)-N-(isoxazol-5-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (25 mg, 0.056 mmol) as a light-yellow solid. 1H NMR (400MHz, DMSO-d6) delta ppm 12.18 (br. s., 1 H), 8.42 (d, J = 2.1 Hz, 1 H), 8.34 (d, J = 2.0 Hz, 1 H), 8.11 (dd, J = 2.0, 8.9 Hz, 1 H), 7.76 (d, J = 8.6 Hz, 1 H), 7.30 (d, J = 2.2 Hz, 1 H), 7.23 (dd, J = 2.2, 8.7 Hz, 1 H), 6.80 (d, J = 8.6 Hz, 1 H), 5.77 (d, J = 1.9 Hz, 1 H), 4.40 - 4.35 (m, 2 H), 3.89 - 3.86 (m, 2 H). m/z (ESI) 451.4 (M+H)+. HRMS m/z Calculated for C19H14F3N4O4S [M+1]+ = 451.0688. Found [M+1]+ = 451.0685.
  • 15
  • [ 32315-10-9 ]
  • 4-(1-fluoro-1-((3-fluorophenyl)sulfonyl)ethyl)piperidine [ No CAS ]
  • [ 14678-05-8 ]
  • 4-(1-fluoro-1-((3-fluorophenyl)sulfonyl)ethyl)-N-(isoxazol-5-yl)piperidine-1-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
42% To a solution of 4-(1-fluoro-1-((3-fluorophenyl)sulfonyl)ethyl)piperidine (6.3, 0.050 g, 0.172 mmol) in THF (1 mL) at 0 C. was added DIEA (0.184 mL, 1.03 mmol) followed by triphosgene (0.017 g, 0.057 mmol). The reaction mixture was stirred for 15 minutes before the <strong>[14678-05-8]isoxazol-5-amine</strong> (0.014 g, 0.172 mmol) was added. The reaction mixture was stirred overnight at room temperature and then was diluted with EtOAc (5 mL) and was quenched with H2O (2 mL). The two layers were separated, and the organic layer was concentrated. The resulting residue was purified using reverse phase high pressure liquid chromatography (0-90% CH3CN in H2O (both containing 0.1% TFA)) to provide the desired product as a white solid (0.015 g, 42%). LC-MS (ES, m/z): 400 [M+H]+; 1H NMR (400 MHz, CDCl3): delta 8.06 (d, J=1.8 Hz, 1H), 7.70-7.62 (m, 1H), 7.60-7.48 (m, 2H), 7.30 (m, 2H), 6.14 (m, 1H), 4.18-4.00 (m, 2H), 2.99-2.83 (m, 2H), 2.62-2.49 (m, 1H), 2.30 (m, 1H), 1.94 (m, 1H), 1.51-1.33 (m, 5H) ppm.
  • 16
  • 5-chloro-7-methoxy-6-(4-methoxyphenyl)-2,3-diphenylpyrazolo[1,5-a]pyrimidine [ No CAS ]
  • [ 14678-05-8 ]
  • 5-(isoxazol-5-ylamino)-6-(4-methoxyphenyl)-2,3-diphenylpyrazolo[1,5-a]pyrimidin-7(4H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
With palladium diacetate; potassium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 100℃; for 1.0h;Inert atmosphere; Microwave irradiation; A suspension of intermediate 5 (100 mg, 0.22 mmol) , <strong>[14678-05-8]isoxazol-5-amine</strong> (23 mg, 0.27 mmol, 1.2 eq. ) , Pd (OAc) 2 (20 mg, 0.09 mmol, 0.4 eq. ) , Xantphos (53 mg, 0.09mmol, 0.4 eq. ) and K2CO3 (63 mg, 0.45 mmol, 2.5eq. ) in dioxnae (4 mL) was stirred at 100 through microwave irradiation for 1 hour under N2 atmosphere. The mixture was filtered through celite and the filtrate was concentrated in vacuo. The residue was purified to afford the title compound as a white solid. 1H NMR (DMSO-d6) : delta 12.38 (br. s., 1H) , 10.40 (br. s., 1H) , 7.24 -7.54 (m, 15H) , 7.00 (d, J 8.1 Hz, 2H) , 3.81 (s, 3H) . LC-MS: m/z 475.9 (M+H) +.
  • 17
  • [ 146514-35-4 ]
  • [ 14678-05-8 ]
  • tert-butyl (4-hydroxy-1-(isoxazol-5-ylamino)-1-oxobutan-2-yl)carbamate [ No CAS ]
 

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