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Chemical Structure| 1179361-84-2 Chemical Structure| 1179361-84-2

Structure of 1179361-84-2

Chemical Structure| 1179361-84-2

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Product Details of [ 1179361-84-2 ]

CAS No. :1179361-84-2
Formula : C6H9N3O2
M.W : 155.16
SMILES Code : O=C(C1=CN=CN1N)OCC
MDL No. :MFCD12755702
InChI Key :LERIOFHGELUHFG-UHFFFAOYSA-N
Pubchem ID :46839655

Safety of [ 1179361-84-2 ]

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

Computational Chemistry of [ 1179361-84-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 5
Fraction Csp3 0.33
Num. rotatable bonds 3
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 38.46
TPSA ?

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

70.14 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.26
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

0.87
Log Po/w (WLOGP)?

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

-0.22
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.

-0.18
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

-0.66
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.21

Water Solubility

Log S (ESOL):?

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

-1.49
Solubility 5.04 mg/ml ; 0.0325 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.

-1.93
Solubility 1.84 mg/ml ; 0.0118 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

-0.52
Solubility 47.2 mg/ml ; 0.304 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.

-6.63 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

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)

2.09

Application In Synthesis of [ 1179361-84-2 ]

* 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 [ 1179361-84-2 ]

[ 1179361-84-2 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 23785-21-9 ]
  • [ 1179361-84-2 ]
YieldReaction ConditionsOperation in experiment
65% Preparation of intermediate II-30; LiHMDS was added to a -10C solution of ethyl imidazole-4-carboxylate in DMF. After 15 min, o-diphenylphosphinylhydroxylamine (CAS: 72804-96-7) was added in one portion and the mixture was stirred at rt for 6 h. The reaction was quenched with water (an exothermic reaction occcurs) until a clear solution is obtained. The solvents were removed under reduced pressure. The residue was dissolved in water and it was extracted with DCM (x3). Combined organic layers were dried and evaporated. The residue was purified on silica gel (biotage, DCM/MeOH 0 to 10% MeOH) to obtain: 356 mg of desired product, intermediate II-30. Yield 65%.
  • 2
  • [ 1179361-84-2 ]
  • 1-amino-1H-imidazole-5-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
91% With ammonia; In methanol; at 70℃; for 48h;Sealed tube; Synthesis of Compound 8.2. Into a 100-mL sealed tube, was placed 8.1 (475 mg, 3.06 mmol, 1.00 equiv), ammonia in methanol (50 mL). The resulting solution was stirred for 48 h at 70 C. The resulting mixture was concentrated in vacuo. This resulted in 350 mg (91%) of l-amino-lH-imidazole-5-carboxamide (8.2) as an off-white solid.
With ammonia; ammonium chloride; In methanol; at 90 - 120℃; for 101h;Closed vessel; Preparation of intermediate II-29; A mixture of intermediate II-30 and NH4CI in 7N NHa/MeOH solution was heated at 90C (sand bath) in a closed vessel for 72h. The reaction was heated at 110C for 24 h. Fresh 7N was added (20 mL) and the reaction was heated at 120C for 5 h. Solvents were evaporated to dryness. The residue was partitioned between EtOAc/water. The organic layer was washed once with water, dried and evaporated to give only 11 mg of residue. The aqueous layer was evaporated to dryness to give 400 mg of a white solid, as a mixture of desired product, intermediate 11-29 and NH4CI salts (yield > 100%) that was used as such in next reaction.
  • 3
  • [ 23785-21-9 ]
  • [ 1179361-84-2 ]
YieldReaction ConditionsOperation in experiment
65% Synthesis of Compound 8.1. Into a 100-mL 3-necked round-bottom flask, was placed ethyl lH-imidazole-5-carboxylate (1.4 g, 9.99 mmol, 1.00 equiv) and N,N- dimethylformamide (25 mL) was added. The reaction was cooled in an ice bath and then LiHMDS (IN in tetrahydrofuran) (11 mL, 1.10 equiv) was added. The reaction was stirred at R.T. Then amino diphenylphosphinate (2.8 g, 12.01 mmol, 1.20 equiv) was added at RT. The reaction was stirred for 2 h at 25 C. Then it was concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with dichloromethane/methanol (100: 1). This provided 1.0 g (65%) of ethyl 1 -amino- lH-imidazole-5-carboxylate (8.1) as an off-white solid.
Ste -2: (0913) Preparation of ethyl 1-amino-1H-imidazole-5-carboxylate: (0914) [00346] To stirred solution of ethyl 1H-imidazole-5-carboxylate (0.1 g, 0.71 mmol) in N,N-dimethylformamide (10 mL) cooled to -10 C, was added lithium bis(trimethylsilyl)amide (0.78 mL, 0.78 mmol) drop wise and the reaction mixture was stirred at -10 C for 15 min. Then (aminooxy)diphenylphosphine oxide (0.199 g, 0.85 mmol) was added at -10 C and the reaction mixture was stirred at room temperature for 6 h. The reaction mixture was quenched by slow addition of water until the precipitate formed was dissolved to become clear solution. Then it was extracted using ethyl acetate (2 x 50 mL). The combined organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to afford the title compound ethyl 1- amino-1H-imidazole-5-carboxylate as off white solid (0.1 g, crude). Calculated (M+H): 156.07; Found (M+H): 156.1.
  • 4
  • [ 1179361-84-2 ]
  • [ 3473-63-0 ]
  • imidazo[5,1-f][1,2,4]triazin-4(3H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
In ethanol; at 85℃; for 16h; Step-3: (0915) Preparation of imidazo[5,1-f][1,2,4]triazin-4(3H)-one: (0916) [00347] To a solution of <strong>[1179361-84-2]ethyl 1-amino-1H-imidazole-5-carboxylate</strong> (0.38 g, 2.44 mmol) in ethanol (20 mL) was added formamidine acetate (1.27 g, 12.25 mmol) and the reaction mixture was heated at 85 C for 16 h. After completion of the reaction, the reaction mixture was cooled to room temperature and the solid obtained was filtered, washed with hexane and dried under high vacuum to afford the title compound imidazo[5,1-f][1,2,4]triazin-4(3H)-one (0.17 g, crude) as a off-white solid. Calculated (M+H): 137.04; Found (M+H): 137.1.
 

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