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Structure of 41864-22-6

Chemical Structure| 41864-22-6

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Product Details of [ 41864-22-6 ]

CAS No. :41864-22-6
Formula : C5H4N6O
M.W : 164.12
SMILES Code : O=C(N1N=CN=C1)N2N=CN=C2
MDL No. :MFCD00043399
InChI Key :YHNUDLCUIKMNSN-UHFFFAOYSA-N
Pubchem ID :4393961

Safety of [ 41864-22-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P280-P305+P351+P338-P310

Computational Chemistry of [ 41864-22-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 10
Fraction Csp3 0.0
Num. rotatable bonds 2
Num. H-bond acceptors 5.0
Num. H-bond donors 0.0
Molar Refractivity 36.24
TPSA ?

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

78.49 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.6
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

0.06
Log Po/w (WLOGP)?

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

-0.61
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.

-0.35
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

-1.4
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.34

Water Solubility

Log S (ESOL):?

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

-1.38
Solubility 6.84 mg/ml ; 0.0417 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.

-1.26
Solubility 8.98 mg/ml ; 0.0547 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

-0.13
Solubility 121.0 mg/ml ; 0.735 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.

-7.26 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)

2.16

Application In Synthesis of [ 41864-22-6 ]

* 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 [ 41864-22-6 ]

[ 41864-22-6 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 41864-22-6 ]
  • [ 147403-65-4 ]
  • [ 147403-52-9 ]
YieldReaction ConditionsOperation in experiment
With 1,8-diazabicyclo[5.4.0]undec-7-ene; In dimethyl sulfoxide; at 20℃; for 3h;Product distribution / selectivity; Example 4Methyl 2-ethoxy- 1 -((2'-(5-oxo-4,5-dihydro- 1 (2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)- 1H- benzo[< ]imidazole-7-carboxylate of formula la l ,8-Diazabicyclo[5.4.0.]undec-7-ene (DBU; 0.1 g, 0.65 mmol) was added dropwise to a mixture of methyl 2-methoxy- l -((2'-((hydroxyamino)iminomethyl)biphenyl-4-yl)methyl)- lH- benzo[i ]imidazole-7-carboxylate (of formula Va; 0.22 g, 0.5 mmol), the corresponding solvent (3 ml) and carbonyldiimidazole (0.1 g, 0.6 mmol) in a reaction vial under stirring and the mixture was stirred at the room temperature for 3 hours. Then, the content of the vial was poured into water ( 10 ml) and, after acidification with acetic acid, the separated solids were aspirated and washed with water. The yields and purity of the products are summarized in Table I. Table I - Yield and purity of the product of Example 4* - Also contains 40.4 percent of the starting compound of formula Va; ** - Carbonyl-di- 1 ,2,4- triazole was used instead of carbonyldiimidazole
  • 2
  • [ 41864-22-6 ]
  • [ 851983-85-2 ]
  • [ 1441047-13-7 ]
YieldReaction ConditionsOperation in experiment
80% In dichloromethane; acetonitrile; for 3h;Reflux; [00170] 3beta-(IotaEta- 1 ,2,4-Triazole- 1-carboxylate)- 17-(lH-benzimidazol- l-yl)-androsta- 5,16-diene (49): A solution of 5 (0.15 g, 0.386 mmol), CDT (0.19 g, 1.16 mmol) in anhydrous acetonitrile (3 mL) and DCM (1.5 mL) was refluxed for 3h. The solvent evaporated, residue treated with water, and extracted with DCM. The crude white product obtained on evaporation of solvent was purified by FCC using 4 percent Ethanol in DCM in presence of traces of TEA (0.06percent). The product was triturated with petroleum ether to give 49 (0.15 g, 80percent> ): mp 205-206 °C; IR (Neat) 2950, 2855, 1776, 1489, 1375, 1289, 978, 750 cm"1; 1H NMR (500 MHz, CDCI3) delta 1.03 (s, 3 H, I8-CH3), 1.12 (s, 3 H, 19-CH3), 4.96 (m, 1 H, 3a-H), 5.52 (m, 1 H, 6-H), 5.99 (s, 1 H, 16-H), 7.30 (m, 2 H, aromatic-Hs), 7.50 (t, 1 H, J = 3.8 Hz, aromatic -H), 7.81 (m, H, aromatic- H), 7.96 (s, 1 H, 2'-H), 8.07 (s, 1 H, 5"-H), and 8.83 (s, 1 H, 3"-H); 13C NMR (500 MHz, CDC13) delta 153.8, 147.3, 145.8, 143,5, 141.8, 139.2, 134.7, 124.3, 123.6, 122.7, 120.4, 111.3, 80.0, 55.9, 50.5, 47.4, 37.9, 37.0, 35.0, 31.3, 30.5, 27.6, 20.8, 19.4, 16.2. HRMS calcd 506.2526 (C29H3302N5.Na+), found 506.2525.
  • 3
  • [ 41864-22-6 ]
  • [ 337915-79-4 ]
  • [ 84712-08-3 ]
YieldReaction ConditionsOperation in experiment
88% With triethylamine; In tetrahydrofuran; at 20℃; for 0.5h;Reflux; 4-bromo-1-n-methylbenzene-1,2-diamine (4.42 g, 21.98 mmol), N,N?-carbonyl-di-(1,2,3-triazole (4.178 g, 24.18 mmol), and TEA (9.184 mL, 65.95 mmol) in THF (70 mL) are stirred at r.t. for 30 min, then heated under reflux overnight. The reaction mixture is concentrated, triturated with water, filtered off and dried. The residue is triturated again with DIPE and filtered off. Yield 88%.
  • 4
  • [ 41864-22-6 ]
  • [ 29608-05-7 ]
  • [ 15996-82-4 ]
  • 1-(4'-chloro-biphenyl-4-ylmethyl)-3-(4-piperidin-1-ylmethyl-phenyl)-urea [ No CAS ]
  • 5
  • [ 41864-22-6 ]
  • [ 474645-27-7 ]
  • C64H68N4O16 [ No CAS ]
  • ORLISTAT [ No CAS ]
YieldReaction ConditionsOperation in experiment
62% (4.86 g) 2-MeTHF (194 mL)1'-Carbonyl-di- (1,2,4-triazole) (CDT)(Sigma-Aldrich, Cat 21861) (2.0 eq.).The reaction mixture was stirred at room temperature for 5 hrs and LC-MS indicated completion of the reaction.The reaction mixture was then washed with water (49 mL x 3) (some NaCl needed for phase separation)(Note: the wet solution was stable overnight) and dried over anhydrous sodium sulfate.Solvent evaporation gave a solid (5.833 g).The solid and 3.646 g (1.3 eq.) Of MMAE were dissolved in 2-MeTHF (29 mL).1-Hydroxybenzotriazole hydrate (HOBt) (0.15 g, 0.2 eq.) In 4 mL 2-MeTHF(Sigma-Aldrich, Cat 711489)Was evaporated to reduce the volume by about 1/2.The concentrated HOBt solution was then added to the reaction mixture,It was stirred at 55 OC for 60 hours.The reaction was washed with water (29 mL x 4) to remove excess MMAE and HOBt.The MMAE can also be removed by stirring with rt in 2-MeTHF solution overnight with polymer-bound isostornic anhydride (Aldrich product 514373).MMAE reacts with the polymer-bound isostornic anhydride, which is then filtered off.The reaction mixture was dried over anhydrous sodium sulfate and the solvent was exchanged with EtOAc and the resulting solution was loaded onto a Biotage column.The product was eluted with 5percent MeOH in EtOAc to give 4.914 g (62percent yield) of compound 4A.
  • 6
  • [ 41864-22-6 ]
  • [ 97682-44-5 ]
  • [ 93930-15-5 ]
  • C49H56N4O11 [ No CAS ]
YieldReaction ConditionsOperation in experiment
63% Hydroxymethylloprolactone(352mg) and1,1'-carbonylbis(1,2,4-triazole) (436 mg) was dissolved in 10 mL of dichloromethane.The reaction was stirred at room temperature for 2 h, then 10 mL of deionized water was added.The mixture was extracted with 50 ml of dichloromethane.The organic layer was washed three times with deionized water (10 mL x 3).It is dried again and concentrated under reduced pressure to give a hydroxy-activated parthenolide intermediate.The intermediate product (152 mg) was added to 10 mL of dichloromethane dissolved in <strong>[97682-44-5]irinotecan</strong> (770 mg) at room temperature, and then the catalyst triethylamine (200 muL) was added thereto, and the reaction was stirred for 48 hours.After adding 10 mL of deionized water, it was extracted with dichloromethane.The organic phase was washed three times with deionized water (10 mL x 3).Wash with 10 mL of saturated sodium chloride solution and dry, filter,The organic solvent was removed to give a crude product.Using dichloromethane/methanol (volume ratio = 20:1) as the eluent,The crude product was purified by column chromatography.The target product 210 mg (yellow solid) was obtained by rotary evaporation.The yield was 63%.
 

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