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Chemical Structure| 31037-02-2 Chemical Structure| 31037-02-2

Structure of 31037-02-2

Chemical Structure| 31037-02-2

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Product Details of [ 31037-02-2 ]

CAS No. :31037-02-2
Formula : C7H11N3O2
M.W : 169.18
SMILES Code : C1=N[N](C(=C1C(OCC)=O)N)C
MDL No. :MFCD00051652
InChI Key :MEUSJJFWVKBUFP-UHFFFAOYSA-N
Pubchem ID :271299

Safety of [ 31037-02-2 ]

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

Computational Chemistry of [ 31037-02-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 5
Fraction Csp3 0.43
Num. rotatable bonds 3
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 43.98
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.

1.59
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

0.66
Log Po/w (WLOGP)?

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

0.19
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

-0.21
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.48

Water Solubility

Log S (ESOL):?

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

-1.42
Solubility 6.51 mg/ml ; 0.0385 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.

-1.71
Solubility 3.31 mg/ml ; 0.0195 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

-0.91
Solubility 20.7 mg/ml ; 0.122 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.

-6.86 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)

1.87

Application In Synthesis of [ 31037-02-2 ]

* 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 [ 31037-02-2 ]

[ 31037-02-2 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 31037-02-2 ]
  • [ 105486-72-4 ]
YieldReaction ConditionsOperation in experiment
81% With tert.-butylnitrite; copper(ll) bromide; In acetonitrile; at 20 - 65℃; for 3.5h; Intermediate 1: (5-Bromo-1-methyl-1H-pyrazol-4-yl)-(octahydro-quinolin-1-yl)methanone; Step 1. ; 5-Bromo-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester; To a mixture of t-butyl nitrite (29.5 mL, 221.5 mmol), cupric bromide (39.7 g, 177.5 mmol), and acetonitrile was added 5-amino-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (25 g, 148 mmol) in portions over 30 minutes. The reaction mixture was stirred at ambient temperature for 2 h, then at 65 C. for 1 h. The mixture was then poured into 6N HCl (400 mL) and extracted with dichloromethane. After concentration in vacuo, the crude residue was purified by flash chromatography with a gradient of 0-20% ethyl acetate/hexanes to give 5-bromo-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (28 g, 81%).
68% With tert.-butylnitrite; copper(ll) bromide; In acetonitrile; at 60℃; for 2h;Inert atmosphere; 5-Amino-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (5.0 g, 29.6 mmol) was added portionwise to a mixture of tert-butyl nitrite (4.57 g, 44.3 mmol) and copper (II) bromide (7.92 g, 35.5 mmol) in acetonitrile (20 mL). The mixture was heated to 60C for 2 h. The resulting mixture was poured into 6M HCl (200 mL) and extracted with dichloromethane (3 x 250 mL). The combined organics was dried on magnesium sulfate and concentrated in vacuo. The crude material was purified by column chromatography (SiO2, 0% to 50% ethyl acetate in hexanes) to afford 5-bromo-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester as an off-white solid (4.7 g, 68%). 1H NMR (CDCl3) : 7.93 (s, 1H), 4.32 (q, J = 7.2 Hz, 2H), 3.92 (s, 3H), 1.36 (t, J = 7.0 Hz, 3H).
66% With tert.-butylnitrite; copper(I) bromide; In acetonitrile; at 65℃; for 24h; Step 1. Synthesis of ethyl 5-bromo-1-methyl-1H-pyrazole-4-carboxylate Copper(II) bromide (99%, 20.0 g, 88.6 mmol) and tert-butyl nitrite (90%, 14.1 mL, 107 mmol) were combined in acetonitrile (65 mL) and heated to 65 C. Ethyl 5-amino-1-methyl-1H-pyrazole-4-carboxylate (10.0 g, 59.1 mmol) was slowly added portion-wise {Caution: gas evolution!} and the reaction was maintained at 65 C. for 24 hours. The mixture was cooled to room temperature, poured into aqueous hydrochloric acid (3 N, 600 mL), diluted with ethyl acetate (300 mL) and stirred for 10 minutes. The aqueous layer was extracted with ethyl acetate (150 mL), and the combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified via silica gel chromatography (Gradient: 5% to 100% ethyl acetate in heptane, with a 5-minute hold at 32%), affording the product as a pale yellow solid. Yield: 9.10 g, 39.0 mmol, 66%. LCMS m/z 233.3 (M+1). 1H NMR (500 MHz, CDCl3) delta 1.36 (t, J=7.1 Hz, 3H), 3.92 (s, 3H), 4.32 (q, J=7.1 Hz, 2H), 7.93 (s, 1H).
  • 2
  • [ 31037-02-2 ]
  • [ 754219-01-7 ]
  • 3
  • [ 60-34-4 ]
  • [ 94-05-3 ]
  • [ 31037-02-2 ]
  • [ 21230-43-3 ]
 

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