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Structure of 2851-13-0

Chemical Structure| 2851-13-0

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Product Details of [ 2851-13-0 ]

CAS No. :2851-13-0
Formula : C9H11N3
M.W : 161.20
SMILES Code : CN(C)C1=NC2=CC=CC=C2N1
MDL No. :MFCD01231011
InChI Key :NMTCCVZABWWGSB-UHFFFAOYSA-N
Pubchem ID :17846

Safety of [ 2851-13-0 ]

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

Computational Chemistry of [ 2851-13-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 9
Fraction Csp3 0.22
Num. rotatable bonds 1
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 50.3
TPSA ?

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

31.92 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.53
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

1.71
Log Po/w (WLOGP)?

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

1.63
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.

1.43
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

1.55
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.57

Water Solubility

Log S (ESOL):?

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

-2.41
Solubility 0.633 mg/ml ; 0.00393 mol/l
Class?

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

Soluble
Log S (Ali)?

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

-2.0
Solubility 1.63 mg/ml ; 0.0101 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

-3.01
Solubility 0.157 mg/ml ; 0.000975 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.

-6.07 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)

1.58

Application In Synthesis of [ 2851-13-0 ]

* 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 [ 2851-13-0 ]

[ 2851-13-0 ] Synthesis Path-Downstream   1~24

  • 1
  • [ 4857-06-1 ]
  • [ 506-59-2 ]
  • [ 2851-13-0 ]
  • 2
  • [ 85-44-9 ]
  • [ 2851-13-0 ]
  • 2-dimethylamino-1<i>H</i>-anthra[2,3-<i>d</i>]imidazole-5,10-dione [ No CAS ]
  • 3
  • [ 4857-06-1 ]
  • [ 124-40-3 ]
  • [ 2851-13-0 ]
YieldReaction ConditionsOperation in experiment
89% In water; N,N-dimethyl-formamide; at 200℃; for 0.5h; Commercially available 2-chloro-1H-benzo[d]imidazole (250 mg, 1.64 mmol) was dissolved in DMF (4.7 mL), dimethylamine (50% aqueous solution, 0.50 mL, 4.92 mmol) was added, and the mixture was stirred with heating at 200C for 30 min in an Emrys Optimizer microwave synthesizer. Water was added to the mixture, and the precipitated crystals were collected by suction filtration to give N,N-dimethyl-1H-benzo[d]imidazole-2-amine (234 mg, 89%). ESIMS m/z: 162 (M + H)+; 1H NMR (270 MHz, DMSO-d6, delta): 3.03 (s, 6H), 6.79-6.97 (m, 2H), 7.07-7.20 (m, 2H), 11.17 (br s, 1H)
  • 4
  • [ 2851-13-0 ]
  • [ 74-88-4 ]
  • [ 101533-35-1 ]
  • 6
  • <i>N</i>''-(2-amino-phenyl)-<i>N</i>,<i>N</i>,<i>N</i>',<i>N</i>'-tetramethyl-guanidine [ No CAS ]
  • [ 2851-13-0 ]
  • 7
  • N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate [ No CAS ]
  • [ 95-54-5 ]
  • [ 2851-13-0 ]
  • 8
  • N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate [ No CAS ]
  • [ 95-54-5 ]
  • N''-(2-aminophenyl)-N,N,N',N'-tetramethylguanidinium hexafluorophosphate [ No CAS ]
  • [ 2851-13-0 ]
  • 9
  • [ 95-54-5 ]
  • [ 79-44-7 ]
  • [ 615-16-7 ]
  • [ 2851-13-0 ]
  • 12
  • [ 615-42-9 ]
  • [ 6145-42-2 ]
  • [ 2851-13-0 ]
  • 13
  • [ 2851-13-0 ]
  • [ 495382-05-3 ]
  • [ 1314090-87-3 ]
  • 14
  • [ 2851-13-0 ]
  • [ 1354955-33-1 ]
  • [ 1354956-35-6 ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); XPhos; In N,N-dimethyl-formamide; at 140 - 150℃; for 0.5h;Microwave; Scheme 3 exemplifies a method of forming compounds of Formula I. Chloro purines (4) (1 mmol) can be coupled with R3-H (for example, wherein R3 is benzimidazol-1-yl) (1.03-1.30 mmol), under Buchwald conditions, for example tris(dibenzylideneacetone)-dipalladium(0) (0.02-0.05 mmol), XPhos (0.10-0.20 mmol), cesium carbonate (2 mmol) in DMF (7-10 mL) with heating under microwave at 140-150 C. for 30 minutes to form purines of Formula I. Formula I purines can be further purified by diluting with EtOAc, filtering the contents of the reaction, concentrating and purifying with flash chromatography or reverse phase HPLC. Formula I purines can be further derivatized in subsequent transformations to functionalize R1, for example by deprotecting any protected functional groups (for example deprotecting BOC-protected amine groups followed by additional steps, such as reductive amination, amide coupling or acylation to form additional compounds of Formula I.Example 131 1-(3-(2-(2-(dimethylamino)-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yloxy)azetidin-1-yl)-2-methylpropan-1-one 131 The compound was prepared from 1-(3-(2-chloro-9-methyl-6-morpholino-9H-purin-8-yloxy)azetidin-1-yl)-2-methylpropan-1-one and <strong>[2851-13-0]N,N-dimethyl-1H-benzo[d]imidazol-2-amine</strong> following General Procedure of Buchwald coupling shown in Scheme 3. 1H NMR (400 MHz, CDCl3) delta 8.29 (s, OH), 7.58 (d, J=7.5 Hz, 1H), 7.49 (d, J=7.8 Hz, 1H), 7.15 (dd, J=11.0, 4.3 Hz, 1H), 7.01 (dd, J=10.1, 4.2 Hz, 1H), 5.58-5.45 (m, 1H), 4.60 (d, J=7.2 Hz, 2H), 4.53-4.39 (m, 2H), 4.31 (d, J=9.6 Hz, 1H), 4.19 (s, 5H), 3.88-3.74 (m, 4H), 3.65 (s, 2H), 3.60 (s, 1H), 3.17 (s, 1H), 2.98 (s, 4H), 2.56-2.42 (m, 1H), 1.14 (d, J=6.8 Hz, 5H). LCMS: M+H+=520.2.
  • 15
  • [ 2851-13-0 ]
  • [ 1257295-02-5 ]
  • [ 1257378-93-0 ]
  • 16
  • [ 4857-06-1 ]
  • [ 68-12-2 ]
  • [ 2851-13-0 ]
  • 17
  • [ 4857-06-1 ]
  • [ 60-34-4 ]
  • [ 2851-13-0 ]
  • 18
  • [ 1122-62-9 ]
  • [ 2851-13-0 ]
  • (E)-2-(1-methyl-2-(1-(pyridin-2-yl)ethylidene)hydrazinyl)-1H-benzo[d]imidazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% In ethanol; at 60℃; for 48.0h; 2-Acetylpyridine (1.12 cm3, 9.9 mmol) was added consecutively by syringe, to a solution of 2-(1-methylhydrazinyl)-1Hbenzo[d]imidazole (1.62 g, 9.9 mmol) in ethanol. The mixture was stirred and heated at 60 C for 48 h. The product was isolated by evaporation of the solvent and recrystallization of the residue from a minimum volume of CH3CN by the gradual addition of diethyl ether. Yield: 83% (2.19 g). ESI-MS: m/z (%) = 266 (100) [L+H]+, 288(30) [L+Na]+. 1H NMR (300 MHz, CD3CN): 8.21 (d, J = 4.5 Hz, 1H),7.73 (d, J = 8.0 Hz, 1H), 7.57 (t, J = 7.8 Hz, 1H), 7.06-7.23 (m, 5H),3.48 (s, 3H, CH3-N), 3.48 (s, 3H, CH3-CN) ppm. 13C NMR (CD3CN,100 MHz): 162.04, 157.09, 155.16, 148.93, 148.72, 136.81, 136.29,127.07, 124.41, 121.62, 77.31, 76.99, 76.54, 40.26, 16.38 ppm. IR (KBr): m(C-H)ar 3075m, 3058s, 3029s, m(CC) 1580m, 1564m,1517w, 1456s; m(CN) 1442s, 1400m, 1346w, 1311s, q(C-H)1198s, 1170vs, 1143m, 1085s, 990s, 952s, 885vs; c(C-H) 837s,806m, 789s, 762m, 735m, 641s, 608s, 548m, 438s, 414s cm1. Anal.Calc. for C15H15N5 (265.32): C, 67.90; H, 5.70; N, 26.4. Found: C,67.82; H, 5.77; N, 26.32%.
  • 19
  • [ 2851-13-0 ]
  • [Ag2((E)-2-(1-methyl-2-(1-(pyridin-2-yl)ethylidene)hydrazinyl)-1H-benzo[d]imidazole)2(CF3SO3)2] [ No CAS ]
  • 20
  • [ 2851-13-0 ]
  • [Ag2((E)-2-(1-methyl-2-(1-(pyridin-2-yl)ethylidene)hydrazinyl)-1H-benzo[d]imidazole)2](PF6)2 [ No CAS ]
  • 21
  • N-benzyl-2-dimethylaminobenzimidazole [ No CAS ]
  • [ 2851-13-0 ]
YieldReaction ConditionsOperation in experiment
67% With triethylsilane; palladium 10% on activated carbon; In tetrahydrofuran; at 20℃; for 48.0h;Inert atmosphere; General procedure: A 16 mL vial with a PTFE/silicone septum and a nitrogen-bubbler line was charged with N-benzylbenzimidazole (208.1 mg, 1.0 mmol), Pd/C (10 wt %, dry powder, reduced) (20 mg) and THF (5 mL). The mixture was treated at rt with triethylsilane (320 muL, 2.0 mmol) and then stirred under nitrogen for 14 h at rt. The mixture was filtered through a 0.45 muM PTFE syringe filter and the filtrate was concentrated in vacuo. The residue was purified by column chromatography (0 to 10% MeOH/ dichloromethane) to afford benzimidazole as a colorless solid (117.6 mg, 0.996 mmol 99%). The reactions generally exhibit an induction period of 5 to 30 min as indicated by the initiation of gas release (i.e., bubbling) from the reaction mixture. The use of Pd/C on a dry matrix is imperative as wet Pd/C results in decreased yield or no reaction.
  • 22
  • [ 95-54-5 ]
  • [ 16420-13-6 ]
  • [ 2851-13-0 ]
YieldReaction ConditionsOperation in experiment
88% With pyridine; copper(l) iodide; sodium hydroxide; at 60℃; for 0.166667h;Microwave irradiation; Green chemistry; Add 1 mmol of o-phenylenediamine to the reaction vessel.Add 0.05 mmol of cuprous iodide sequentially.1 mmol of sodium hydroxide, N,N-dimethylaminothioformyl chloride 2.5 mmol,3 ml pyridine.Heated to 60 C at 120 W in a microwave reactorContinuous reaction for 10 min.After the reaction is completed, it is cooled to room temperature.Concentrated under reduced pressure,The product is purified by column chromatography.A white solid was obtained in 88% yield.
87% With iron(III) chloride; caesium carbonate; In tetrahydrofuran; at 60℃; for 5.0h;Green chemistry; Add 1 mmol of o-phenylenediamine to the reaction vessel.Add 0.1 mmol of ferric chloride in sequence,Cesium carbonate 1 mmol,N,N-dimethylaminothioformyl chloride 2.5 mmol,3 ml of tetrahydrofuran. Heat to 60 C for 5 h. After the reaction is completed, it is cooled to room temperature.Concentrated under reduced pressure, the product was purified by column chromatography.A white solid was obtained in a yield of 87%.
  • 23
  • [ 13636-27-6 ]
  • [ 2851-13-0 ]
  • 24
  • [ 62-53-3 ]
  • [ 2851-13-0 ]
 

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Technical Information

Categories

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[ 2851-13-0 ]

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