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Chemical Structure| 1072-68-0 Chemical Structure| 1072-68-0

Structure of 1072-68-0

Chemical Structure| 1072-68-0

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Product Details of [ 1072-68-0 ]

CAS No. :1072-68-0
Formula : C5H8N2
M.W : 96.13
SMILES Code : C1=N[N](C=C1C)C
MDL No. :MFCD01075158
InChI Key :SZQCPPRPWDXLMM-UHFFFAOYSA-N
Pubchem ID :136836

Safety of [ 1072-68-0 ]

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

Computational Chemistry of [ 1072-68-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 7
Num. arom. heavy atoms 5
Fraction Csp3 0.4
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 28.46
TPSA ?

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

17.82 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.47
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

0.6
Log Po/w (WLOGP)?

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

0.73
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

0.83
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.8

Water Solubility

Log S (ESOL):?

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

-1.34
Solubility 4.37 mg/ml ; 0.0454 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.

-0.55
Solubility 27.2 mg/ml ; 0.283 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

-1.1
Solubility 7.67 mg/ml ; 0.0798 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.

-6.46 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)

1.07

Application In Synthesis of [ 1072-68-0 ]

* 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 [ 1072-68-0 ]

[ 1072-68-0 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 1072-68-0 ]
  • [ 61676-62-8 ]
  • [ 1047644-76-7 ]
YieldReaction ConditionsOperation in experiment
To a suspension of NaH (60% in mineral oil, 3.5 g, 146 mmol, washed with 200 mL of hexane) in THF (200 mL) was added 4-methyl-1 H-pyrazole (10 g, 122 mmol) at 0 0C dropwise. After stirring at RT for 1 h, to above suspension was added MeI (7.3 mL, 117 mmol) dropwise at 0 0C. The reaction mixture was stirred overnight. The NaI by-product was removed by filtration and the filtrate solution was used directly in the next step.At 00C, to above THF solution of 1 ,4-dimethyl pyrazole was added n-BuLi (2.5M in hexane, 58.5 mL, 146 mmole). The reaction solution was stirred for 2 hour at RT and then cooled to -78C [J. Heterocyclic Chem. 41 , 931 (2004)]. To the reaction solution was added 2-isopropoxy-4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane (27.2 g, 146 mmole). After 15 min at -78C, the reaction was allowed to warm to 00C and stir for 3h. The reaction was diluted with saturated NH4CI solution and extracted with DCM. The organics were dried over Na2SO4 and concentrated under vacuum to afford the title compound as a brown solid (21 g, 78%) which was used directly without further purification: LC-MS: 141 (M-C6H12)"1", 223 (M+H)+. 1H NMR (CDCI3): delta 7.28 (s, 1 H), 4.03 (s, 3H), 2.22 (s, 3H), and 1.32 (s, 12H).
142 mg 1,4-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole A solution of 1,4-dimethyl-1H-pyrazole (480.0 mg, 4.993 mol) in tetrahydrofuran (20 mL, 300 mmol) at 0 C. was added 1.6 M n-butyllithium in hexane (4.7 mL, 7.5 mmol). The solution was stirred at room temperature for 1 h and then cooled to -78 C. To the solution was added 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.63 mL, 7.99 mmol). The reaction mixture was stirred at -78 C. for 0.5 h, then warmed up to 0 C. (taking 0.5 h). The reaction was quenched with brine and extracted with EtOAc (3*). The combined organic phases were washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by combi-flash chromatography and eluted with EtOAc/hexane (0-60%). The purification gave 142 mg of product as white solid.
Step 1. 1, 4-Dimethyl-5-( 4, 4, 5, 5-tetrame orolan-2-yl)-lH-pyrazole l,4-Dimethyl-7H-pyrazole (50 mg, 0.5 mmol) was stirred in THF (2 mL) and cooled to 0 C. A solution of 1.6 M w-butyllithium in hexanes (390 mL) was added dropwise by syringe and the mixture was allowed to warm to room temperature for 2 h. The mixture was cooled to -78 C and 2-isopropoxy-4,4,5,5-tetramethyl-l,3,2-dioxaborolane(110 mL, 0.52 mmol) was added dropwise by syringe. The mixture was stirred at -78 C for 15 min. and at 0 C for 3 h. The mixture was diluted with EtOAc and washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification by chromatography on silica gel using EtOAc in hexanes gave the sub-title compound. LCMS calc. for CnH2oB 202 (M+H)+: m/z = 223.2; found: 223.0.
With n-butyllithium; Step 1 To a solution of 1,4-dimethyl-1H-pyrazole (2.5 g, 26.0 mmol, 1 equiv) in tetrahydrofuran (50 mL) was added n-butyllithium in hexane solution (2.5 M in hexane, 78.0 mmol, 31 mL, 3 equiv) dropwise at 0 C. under nitrogen atmosphere. The resulting solution was stirred at room temperature for 1 h and then cooled to -78 C. 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (14.52 g, 78.017 mmol, 3 equiv) was added and the reaction mixture was stirred at -78 C. for 0.5 hour, then slowly warmed up to 0 C. The reaction was quenched with brine and extracted with EtOAc (250 mL*3). The combined organic layer was washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The residue was applied onto a silica gel column eluting with ethyl acetate/petroleum ether (1:5). This resulted in 2.6 g (45%) of 1,4-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole as a white solid.

  • 2
  • [ 1072-68-0 ]
  • [ 802919-90-0 ]
  • [ 1609470-39-4 ]
 

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