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Chemical Structure| 1001020-17-2 Chemical Structure| 1001020-17-2

Structure of 1001020-17-2

Chemical Structure| 1001020-17-2

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Product Details of [ 1001020-17-2 ]

CAS No. :1001020-17-2
Formula : C8H12N2O
M.W : 152.19
SMILES Code : O=CC1=CNN=C1C(C)(C)C
MDL No. :MFCD07186448
InChI Key :JQCJTNPAWAQSFC-UHFFFAOYSA-N
Pubchem ID :3159701

Safety of [ 1001020-17-2 ]

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

Computational Chemistry of [ 1001020-17-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 5
Fraction Csp3 0.5
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 43.25
TPSA ?

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

45.75 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.12
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

1.39
Log Po/w (WLOGP)?

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

1.52
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.

0.44
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

2.13
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.32

Water Solubility

Log S (ESOL):?

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

-1.86
Solubility 2.08 mg/ml ; 0.0137 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.

-1.95
Solubility 1.69 mg/ml ; 0.0111 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

-2.38
Solubility 0.639 mg/ml ; 0.0042 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

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.

-6.24 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

1.0 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)

1.7

Application In Synthesis of [ 1001020-17-2 ]

* 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 [ 1001020-17-2 ]

[ 1001020-17-2 ] Synthesis Path-Downstream   1~4

  • 1
  • pinacolone semicarbazone [ No CAS ]
  • [ 68-12-2 ]
  • [ 1001020-17-2 ]
YieldReaction ConditionsOperation in experiment
6% b) 3-Te/t-butyM /-/-pyrazole-4-carbaldehydePhosphorus oxychloride (18.2 ml_, 195 mmol) was added portionwise to DMF (30 ml_, 387 mmol) at < 5 0C. Pinacolone semicarbazone (15.4 g, 97.6 mmol) was added over 1 h maintaing the temperature at < 5 0C. The reaction mixture became very thick so an additional quantity of DMF (10 mL) was added. The mixture was heated to 60 0C for 3.5 h then allowed to cool and poured into ice. The reaction was neutralised using sodium hydroxide (40 g, 1 mol) in water (130 mL) then heated at 60 0C for 5 min. The mixture was <n="66"/>cooled in an ice bath and acidified to pH 6 and the product extracted into EtOAc. The EtOAc was dried over MgSO4 and concentrated onto silica. The crude product was purified by flash chromatography using elutants EtOAc/heptane. Trituration in diethyl ether gave a white solid (1.02 g, 6.1 mmol, 6 %). 1 H NMR (400MHz, CDCI3): delta 1.48 (s, 9H), delta 8.07 (s, 1 H)1 delta 10.06 (s, 1 H) delta 10.25 (b, 1 H).
  • 2
  • [ 1001020-17-2 ]
  • [ 1001020-10-5 ]
  • 2-(2-(3-tert-butyl-4-formyl-1H-pyrazol-1-yl)acetamido)-N-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
91% With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 3h; Example 78 2-(2-(3-7erf-butyl-4-formyl-1H-pyrazol-1-vnacetan?ido)-N-nnethyl-4,5.6,7- tetrahvdrobenzofblthiophene-3-carboxannide3-Terf-butyl-1H-pyrazole-4-carbaldehyde (150 mg, 0.986 mmol), 2-(2-bromoacetamido)- N-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxannide (490 mg, 1.478 mmol) and potassium carbonate (545 mg, 3.94 mmol) were mixed with DMF (5 ml_) and heated for 3 h at 60 0C. The reaction was partitioned between water and EtOAc. Organics were combined and purified by chromatography (0-60%, EtOAc/heptane) to give the title product as a white solid (360 mg, 0.894 mmol, 91 %). MS (ESI): m/z 403.6 [M + H]+.
  • 3
  • [ 1001020-17-2 ]
  • [ 1001020-23-0 ]
  • 2-(2-(3-tert-butyl-4-formyl-1H-pyrazol-1-yl)acetamido)-N-(2-hydroxyethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% Example 842-(2-(3-rert-butyl-4-formyl-1H-pyrazol-1-vhacetamido)-N-(2-hvdroxyethvn-4.5.6.7- tetrahvdrobenzofbithiophene-3-carboxamide <n="78"/>2-(2-Bromoacetamido)-N-(2-hydroxyethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3- carboxamide (1.66 g, 4.60 mmol), 3-tert-butyl-1 H-pyrazole-4-carbaldehyde (1.75 g, 11.49 mmol) and potassium carbonate (2.54 g, 18.38 mmol) were mixed with DMF (20 ml_) and heated at 70 CC for 2 h. On cooling, the reaction was partitioned between EtOAc and water. The organics were washed with brine, dried over MgSO4 and concentrated directly onto silica for chromatographic purification (0-100 % EtOAc/heptane). Concentration in vacuo yielded a white solid (1.64 g, 3.79 mmol, 83 %). MS (ESI): m/z 433.5 [M + H]+.
  • 4
  • [ 1001020-17-2 ]
  • [ 74-88-4 ]
  • C9H14N2O [ No CAS ]
  • C9H14N2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In N,N-dimethyl-formamide; at 85℃; for 3h; A mixture of A-i (750 mg, 4.93 mmol), A-2 (0.46 mL, 7.39 mmol) and K2C03 (2.72 g, 19.71 mmol) in 10 mL DMF is heated at 85 C for 3 hours. The reaction mixture is diluted with EtOAc, washed with water, brine, dried over Na2SO4, concentrated in vacuo. The residue is purified by column chromatography on silica gel eluting with 10-100% EtOAc in heptane to yield Intermediates A and B as a 10:1 mixture by 1HNMR.
 

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Technical Information

Categories

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