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Structure of 55314-16-4

Chemical Structure| 55314-16-4

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Product Details of [ 55314-16-4 ]

CAS No. :55314-16-4
Formula : C10H12N2O
M.W : 176.22
SMILES Code : N1=CC(=CC=C1)C(C=CN(C)C)=O
MDL No. :MFCD00115180
InChI Key :MZLRFUCMBQWLNV-FNORWQNLSA-N
Pubchem ID :5369165

Safety of [ 55314-16-4 ]

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

Computational Chemistry of [ 55314-16-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 6
Fraction Csp3 0.2
Num. rotatable bonds 3
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 51.27
TPSA ?

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

33.2 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.81
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

0.86
Log Po/w (WLOGP)?

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

1.34
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.

0.12
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

1.27
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.08

Water Solubility

Log S (ESOL):?

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

-1.62
Solubility 4.25 mg/ml ; 0.0241 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.

-1.14
Solubility 12.7 mg/ml ; 0.0723 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

-2.17
Solubility 1.19 mg/ml ; 0.00675 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.

-6.76 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

1.0 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)

2.1

Application In Synthesis of [ 55314-16-4 ]

* 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.

  • Downstream synthetic route of [ 55314-16-4 ]

[ 55314-16-4 ] Synthesis Path-Downstream   1~13

  • 3
  • [ 55314-16-4 ]
  • [ 1450-93-7 ]
  • 5-(pyridin-3-yl)imidazo[1,2-a]pyrimidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium acetate; In hexane; acetic acid; EXAMPLE 1 5-(3-Pyridyl)imidazo[1,2-a]pyrimidine A mixture of 5.29 g of <strong>[1450-93-7]2-aminoimidazole hemisulfate</strong>, 3.28 g of anhydrous sodium acetate and 7.04 g of 3-dimethylamino-1-(3-pyridyl)-2-propen-1-one (prepared according to the procedure of Example 1 in U.S. Pat. No. 4,281,000) in 100 ml of glacial acetic acid was heated under reflux for 16 hours. The solvent was removed in vacuo. The solid residue was made basic with saturated aqueous sodium bicarbonate, then was extracted with dichloromethane. The dichloromethane solution was passed through a short column of a hydrous magnesium silicate. The effluent was refluxed on a steam bath with the gradual addition of hexane until crystallization was noted. On cooling, the desired compound was separated and collected by filtration and gave 2.54 g of yellow prisms, mp 162°-164° C.
  • 4
  • [ 50-01-1 ]
  • [ 55314-16-4 ]
  • [ 66521-66-2 ]
  • 5
  • [ 593-85-1 ]
  • [ 55314-16-4 ]
  • [ 66521-66-2 ]
YieldReaction ConditionsOperation in experiment
66% With sodium hydroxide; In butan-1-ol; at 120℃; for 2h; NaOH (0.78 g, 19.5 mmol) was added to a mixture of 3-(dimethylamino)-l-(pyridin-3- yl)prop-2-en-l-one (3.52 g, 20.0 mmol) and guanidine carbonate (1.80 g) in n-butanol (20 mL). The mixture was heated at 1200C for 2 h. After cooling, the precipitates formed was collected by filtration and dried under vacuum to afford the desired product (2.3g, 66percent). LCMS: (M+H)+= 173.2.
In iso-butanol; for 24h;Heating / reflux; 4-Pyridin-3 - yl-pyrimidin-2- ylamine (7)[0042] A mixture of 3-acetylpyridine (20.72 g, 171.0 mmol) and N, N-dimethylformamide dimethyl acetal (60 mL, 450 mmol) is heated at 110 0C. After reaction overnight, the reaction mixture is cooled to room temperature and concentrated. Ethyl ether (20 mL) and hexanes (60 <n="17"/>P A T E N TGNF Docket No.: P1286PC10mL) are added to the residue. The resulting solid is collected by filtration, washed with hexanes, and dried to afford 3-dimethylamino-l-pyridin-3-yl-propenone which is used for next reaction without further purification. A mixture of 3-dimethylamino-l-pyridin-3-yl-propenone (17.6 g, 100 mmol) and guanidine carbonate (10.8 g, 60.0 mmol) in 2-butanol (100 mL) is heated at reflux. After 24 hours, the reaction mixture is cooled to room temperature and concentrated. The residue is triturated in water (50 mL). The solid is collected by filtration, washed with water and dried to afford the desired product 4-pyridin-3-yl-pyrimidin-2-ylamine as a white solid. C29H31N7O Exact MS: 172.07. Found MS m/z 173.1 (M+l). 1H NMR (DMSO-J6): delta 9.23 (s, IH), 8.69 (m, IH), 8.37 (m, 2H), 7.54 (d, IH), 7.20 (d, IH), 6.80 (s, 2H).
  • 6
  • [ 50-01-1 ]
  • [ 55314-16-4 ]
  • [ 66521-66-2 ]
YieldReaction ConditionsOperation in experiment
90% With sodium hydroxide; In tert-butyl alcohol; at 85℃; The starting material was added 3-dimethylamino-1-(3-pyridyl)-2-propen-1-one (Compound 4) (1.76 g, 0.01 mol) in a three-neck flask.Guanidine hydrochloride (2.87 g, 0.03 mol)And sodium hydroxide (1.2g, 0.03mol), add 25ml of solvent t-butanol, stir, heated in a constant temperature oil bath to 85 C reflux reaction, 6-8h. After the reaction is completed, the solvent is spin-dried, an appropriate amount of water and ethyl acetate are added, the insoluble solid is filtered, and the filter cake is washed with water and dried to obtain a yellow solid; the filtrate is further subjected to extraction, the organic phase is collected, dried, and the solvent is dried and dried. The solid was subjected to column chromatography to give a pale yellow solid, Compound 5 (1.55 g, yield: 90%).
With sodium hydroxide; In butan-1-ol; at 120℃; To aflask 3-dimethylamino-1-(3-pyridyl)-2-propen-1-one(1.76 g, 10.0 mmol), guanidine hydrochloride (1.15 g, 12.0 mmol), NaOH (480 mg,12.0 mmol) and n-BuOH (20 mL) were added. The mixturewas heated to 120 oC.The resulting solid was collected, rinsed with water (50 mL) and dried overhigh vacuum to get the product as light yellow crystalline (1.51 g, 88% yield).1H NMR(400 MHz, DMSO) delta 9.23 (d, J = 2.0 Hz, 1H), 8.67 (dd, J = 4.7,1.3 Hz, 1H), 8.38 (dt, J = 8.0, 1.8 Hz, 1H), 8.36 (d, J = 5.1 Hz,1H), 7.52 (dd, J = 8.0, 4.8 Hz, 1H), 7.20 (d, J = 5.1 Hz, 1H),6.81 (s, 2H).13C NMR (101 MHz, DMSO) delta163.78, 161.53, 159.36, 151.11, 147.93, 134.11, 132.44, 123.72, 105.99
With sodium hydroxide; In butan-1-ol; at 120℃; 3-dimethylamino-1-(3-pyridyl)-2-propenyl-1-one (1.76 g, 10.0 mmol) was suspended in n-butanol (20 mL), followed by the addition of guanidine hydrochloride (1.15 g, 12.0 mmol) and NaOH (480 mg, 12.0 mmol). The mixture was heated to 120 C for reacting overnight. The precipitated solid was collected and washed with water (50 mL), followed by vacuum drying to give a light yellow crystal (1.51g, 88% yield). 1H NMR (400 MHz, DMSO) delta 9.23 (d, J = 2.0 Hz, 1H), 8.67 (dd, J = 4.7, 1.3 Hz, 1H), 8.38 (dt, J = 8.0, 1.8 Hz, 1H),8.36 (d, J = 5.1 Hz, 1H), 7.52 (dd, J = 8.0, 4.8 Hz, 1H), 7.20 (d, J = 5.1 Hz, 1H), 6.81 (s, 2H). 13C NMR (101 MHz, DMSO) delta 163.78, 161.53, 159.36, 151.11, 147.93, 134.11, 132.44, 123.72, 105.99
  • 7
  • [ 506-93-4 ]
  • [ 55314-16-4 ]
  • [ 66521-66-2 ]
YieldReaction ConditionsOperation in experiment
85% With sodium hydroxide; In butan-1-ol; for 16h;Reflux; 3-(Dimethylamino)-1-(pyridine-3-yl) prop-2-en-1-one (15.4 g, 0.088 mol), guanidine nitrate (10.7 g, 0.088 mol), and sodium hydroxide (3.5 g, 0.088 mol) were dissolved in n-butanol (120 mL). The mixture was heated to reflux with stirring and maintained for 16 hours. The reaction mixture was then cooled to room temperature. The solid was collected and washed with water (400 mL). The desired product was dried under vacuum for three days and 12.7 g of yellow crystals of desired product was obtained (yield: 85percent); 1H NMR (500 MHz, CDCl3) delta 5.15 (br., 2H), 7.09 (d, 1H), 7.44 (in, 1H), 8.33 (d, 1H), 8.42 (d, 1H), 8.73 (d, 1H), 9.22 (s, 1H). LC-MS (m/z) calculated, 172.2, found 173.2 [M+H]+.
1.18 g With sodium hydroxide; In butan-1-ol; at 90℃; for 0.333333h;Microwave irradiation; The obtained compound 3 followed by 3-(dimethylamino)-1-(pyridin-3-yl) prop-2-en-1-one (0.1 mol), guanidine nitrate(0.1 mol), sodium hydroxide (0.1 mol), and n-butanol (12.5 mL) was irradiated in the microwave synthesizer at 90 C for 20 min. Aftercompletion of the reaction mixture poured into ice-cold water andthe resulting solid was filtered and washed with water. The obtainedsolid of compound 4 (1.18 g) was dried under vacuum.Melting point 190-192 °C, ES-MS (M1) found (m/z): 173.1.
  • 8
  • [ 420-04-2 ]
  • [ 55314-16-4 ]
  • [ 88-74-4 ]
  • [ 66521-66-2 ]
  • 9
  • [ 28710-97-6 ]
  • [ 55314-16-4 ]
  • [ 1081130-33-7 ]
  • 10
  • guanidine nitrate [ No CAS ]
  • [ 55314-16-4 ]
  • [ 66521-66-2 ]
  • 11
  • [ 506-93-4 ]
  • [ 55314-16-4 ]
  • [ 66521-66-2 ]
YieldReaction ConditionsOperation in experiment
93% In butan-1-ol; for 12h;Reflux; General procedure: A mixture of compound 5 (1 mmol), guanidine nitrate (2 mmol), anhydrous K2CO3 (5 mmol) in n-butanol (10 ml) was refluxed for 12 h. After cooling, the solution was poured into H2O (30 ml) and then extracted with ethyl acetate (3x20 ml). The combined organic layer was concentrated in vacuo and then purified by recrystallisation with diethyl ether.
  • 13
  • [ 55314-16-4 ]
  • [ 483324-01-2 ]
 

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