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Structure of 304693-70-7

Chemical Structure| 304693-70-7

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Product Details of [ 304693-70-7 ]

CAS No. :304693-70-7
Formula : C7H10N2O2
M.W : 154.17
SMILES Code : O=CC1=CN(CCOC)N=C1
MDL No. :MFCD13248693
InChI Key :OZCYWOQGSFDUNP-UHFFFAOYSA-N
Pubchem ID :23033398

Safety of [ 304693-70-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 304693-70-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 5
Fraction Csp3 0.43
Num. rotatable bonds 4
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 39.58
TPSA ?

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

44.12 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.42
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

-0.52
Log Po/w (WLOGP)?

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

0.34
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.

-0.75
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

0.63
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.22

Water Solubility

Log S (ESOL):?

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

-0.54
Solubility 44.4 mg/ml ; 0.288 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.

0.06
Solubility 178.0 mg/ml ; 1.15 mol/l
Class?

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

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

-1.28
Solubility 8.09 mg/ml ; 0.0525 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.

-7.61 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)

1.79

Application In Synthesis of [ 304693-70-7 ]

* 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 [ 304693-70-7 ]

[ 304693-70-7 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 304693-68-3 ]
  • [ 304693-70-7 ]
YieldReaction ConditionsOperation in experiment
With trichlorophosphate; In N,N-dimethyl-formamide; at 90 - 100℃; for 3.0h; Intermediate B6-1-(2-Methoxyethyl)pyrazole carboxaldehyde A solution of 1-(2-methoxyethyl)pyrazole (7.27 g) in dry DMF (11.4 ml) was heated to 90 C., then phosphorus oxychloride (5.4 ml) was added dropwise over 1 hour, maintaining the temperature between 95-100 C. After heating for a further 2 hours, the mixture was cooled and poured onto ice.Sodium hydroxide was added to adjust the mixture to PH 4, then the product was extracted into dichloromethane.Drying and evaporation of the organic extracts yielded a brown oil (7.19 g).1H-NMR (CDCl3) delta 3.34 (3H,s), 3.75 (2H,m), 4.32 (2H,m), 7.98 (1H,s), 8.02 (1H,s), 9.85 (1H,s).
  • 3
  • [ 304693-70-7 ]
  • C14H15F3N4S [ No CAS ]
  • [ 1068-55-9 ]
  • C24H31F3N6OS [ No CAS ]
YieldReaction ConditionsOperation in experiment
26% In a sealed tube, under N2, intermediate 35 (211 mg; 1.37 mmol) and Ti(OiPr)4 (436 jiL; 1.83 mmol) were added to a solution of intermediate 11(300mg; 0.914 mmol) in THF(6 mL). The solution was stirred at 50C for 5 hours then at rt overnight. The reaction mixture was cooled to 5C and isopropyl magnesium chloride 2M in THF (2.28 mL; 4.57 mmol) was added dropwise. The reaction mixture was allowed to rise slowly to rt and stirred overnight. The reaction mixture was diluted with EtOAc and poured onto a 10% aqueous solution of K2C03. The precipitate was removed by filtration over Celite. Theorganic layer was decanted, washed with brine, dried over MgSO4, filtered and evaporated to dryness. The residue was purified by chromatography over silica gel (irregular SiOH, 40g; mobile phase: gradient from 0% MeOH, 100% DCM to 10% MeOH, 90% DCM). The fractions containing the product were collected and evaporated to dryness to give 0.337 g of an intermediate residue which was purified again bychromatography via reverse phase (stationary phase: YMC-actus Triart C18 lOjim30*150mm, mobile phase: gradient from 55% NH4HCO3 0.2%, 45% ACN to 0%NH4HCO3 0.2%, 100% ACN). The pure fractions were collected and evaporated todryness. The residue was freeze-dried with acetonitrile/water 20/80 to afford 120 mg(26%) of compound 71.
  • 4
  • [ 35344-95-7 ]
  • [ 6482-24-2 ]
  • [ 304693-70-7 ]
YieldReaction ConditionsOperation in experiment
65% With caesium carbonate; In N,N-dimethyl-formamide; at 60℃; To a solution of lH-pyrazole-4-carbaldehyde (500 mg, 5.20 mmol) in DMF (20 mL) was added l-bromo-2-methoxyethane (713 mg, 5.2 mmol) and CS2CO3 (3.40 g, 10.4 mmol). After stirring at 60 °C overnight, water (20 mL) was added to the mixture and the mixture was extracted with EtOAc (50 ml x 3). The organic phase was washed with brine, dried over Na2S04 and concentrated to yield intermediate 50 (520 mg, 65percent> yield).
55% With caesium carbonate; In acetonitrile; for 2h;Reflux; 1H-pyrazole-4-carbaldehyde (0.5 g; 5.2 mmol) and cesium carbonate (3.39 g; 10.4mmol) were diluted in ACN (10 mL). Then, 2-bromoethyl methyl ether (0.636 mL; 6.77 mmol) was added and the reaction mixture was refluxed for 2 hours. The reaction mixture was partitionned between a saturated solution of NaHCO3 and EtOAc. The organic layer was separated, dried over MgSO4, filtered and concentrated.The residue was purified by silica gel chromatography (irregular Si02, 120 g, DCM/MeOH: 100/0 to 95/5). The fractions containing the product were mixed andconcentrated to afford 439 mg (55percent) of intermediate 35.
  • 5
  • [ 304693-70-7 ]
  • (x)C2HF3O2*C15H17F3N4S [ No CAS ]
  • C22H27F3N6OS [ No CAS ]
YieldReaction ConditionsOperation in experiment
24.6% With sodium tris(acetoxy)borohydride; In dichloromethane; at 20℃; To a solution of Intermediate 47 (300 mg, 0.44 mmol) in dichloromethane (5 mL) was added intermediate 50 (80.0 mg, 0.530 mmol) and NaBH(OAc)3 (186 mg, (0941) 0.880 mmol). After stirring at room temperature overnight, the mixture was concentrated to give a residue which was purified by prep-HPLC (Waters 2767/Qda, Column: Waters Xbridge 19* 150mm lOum, Mobile Phase A: H20 (0.1%NH4OH), B: ACN) to yield Compound 97 (53.0 mg, 24.6% yield) as yellow oil. (0942) NMR CDCI3 (400 MHz): delta 8.42 (s, 1H), 7.42 (s, 1H), 7.38 (s, 2H), 4.26 (t, J= 5.2 Hz, 2H), 3.91-3.83 (m, 3H), 3.75-3.73 (m, 3H), 3.64 (q, J= 10.4 Hz, 2H), 3.43 (s, 2H), 3.33 (s, 3H), 2.54-2.49 (m, 4H), 2.37-2.32 (m, 2H), 1.86-1.80 (m, 1H), 1.70-1.63 (s, 1H).
 

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