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Structure of 34916-10-4

Chemical Structure| 34916-10-4

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Product Details of [ 34916-10-4 ]

CAS No. :34916-10-4
Formula : C7H9NO
M.W : 123.15
SMILES Code : N#CC1CCC(CC1)=O
MDL No. :MFCD11847831
InChI Key :QIWQJGMBIABGRX-UHFFFAOYSA-N
Pubchem ID :12235639

Safety of [ 34916-10-4 ]

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

Computational Chemistry of [ 34916-10-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 0
Fraction Csp3 0.71
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 33.6
TPSA ?

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

40.86 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.17
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

0.12
Log Po/w (WLOGP)?

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

1.27
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.

0.31
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

1.62
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.9

Water Solubility

Log S (ESOL):?

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

-0.68
Solubility 25.8 mg/ml ; 0.209 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.

-0.53
Solubility 36.0 mg/ml ; 0.293 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

-1.25
Solubility 6.99 mg/ml ; 0.0568 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.

-6.97 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)

1.56

Application In Synthesis of [ 34916-10-4 ]

* 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.

  • Upstream synthesis route of [ 34916-10-4 ]
  • Downstream synthetic route of [ 34916-10-4 ]

[ 34916-10-4 ] Synthesis Path-Upstream   1~8

  • 1
  • [ 69947-09-7 ]
  • [ 34916-10-4 ]
YieldReaction ConditionsOperation in experiment
95% With hydrogenchloride; boric acid In tetrahydrofuran; water at 60℃; for 2 h; Add 1,4-dioxaspiro[4,5]nonane-8-carbonitrile 200.6 g (1.2 mol), boric acid 72 g (1.2 mol), water 2000 mL (10 V), hydrochloric acid in a 5000 mL three-necked flask. 1000 mL (5 V), tetrahydrofuran 500 mL (2.5 V), heated to 60 ° C,The reaction was carried out for two hours, sampled, and sent to the GC for detection. The remaining amount of the raw material was <2percent, and the reaction was completed.Decrease to room temperature, add dichloromethane, extract three times, combine the dichloromethane layer, distill off the dichloromethane under reduced pressure, and rectify the product under the condition of 100 ° C 2 mmHg.4-cyanocyclohexanone 140.4 g, GC purity 98percent, yield 95percent.
87% With trifluoroacetic acid In dichloromethane at 20℃; for 16 h; A solution of R-06i-2 (7.00 g, 41.87 mmol) in TFA (50 mL) and DCM (50 mL) was stirred at 20 °C for 16 hours. Then, the mixture was concentrated to give the crude product. The crude product was purify by column chromatography (Si02, Petroleum ether/Ethyl acetate = 10/1 to 5/1 ) to obtain R-06i-3 (4.50 g, 87percent) as yellow oil. This compound was used in the next step without further characterization.
75% With ammonium cerium(IV) nitrate In water; acetonitrile at 70℃; for 0.75 h; 4-OxocyclohexanecarbonitriIeA solution of ammonium cerium (IV) nitrate (3.70 g, 6.75 mmol) in water (100 mL) was added to a solution of l,4-dioxaspiro[4.5]decane-8-carbonitrile (11.3 g, 67.5 mmol) in MeCN (200 mL) and water (100 mL) at 700C. The reaction mixture was stirred for 45 minutes at 7O0C and cooled to ambient temperature where 100 mL of water were added. The product was extracted with ether (4 x 200 mL). The combined organics were EPO <DP n="10"/>washed with brine and dried over MgSO4. The product was purified by flash chromatography on silica gel using EtOAc 50percent in hexane as eluent to afford the title compound as a colorless liquid. Yield: 6.30 g (75percent). 1H NMR (400 MHz, CHLOROFORM-D): δ 2.07 - 2.31 (m, 4 H), 2.34 - 2.53 (m, 2 H), 2.54 - 2.72 (m, 2 H), 2.95 - 3.14 (m, I H).
68% With hydrogenchloride In water at 20℃; for 2 h; Step 2: A mixture of compound 116-1 (3 g, 18 mmol) in conc. hydrochloric acid / H2O (v/v = 1:1, 20 mL) wasstirred at room temperature for 2h. The reaction mixture was adjusted to pH = 8 with NaOH, and extracted with EtOAc.The combined extraction liquid was washed with brines, dried over sodium sulfate and concentrated to dry, finally purifiedby column chromatography (PE:EtOAc = 1:1) to deliver compound 116-3 (1.5 g, yield 68percent) as colorless oil.

References: [1] Patent: CN108329234, 2018, A, . Location in patent: Paragraph 0018-0022.
[2] Patent: WO2018/229139, 2018, A1, . Location in patent: Page/Page column 46; 47.
[3] Patent: WO2007/13848, 2007, A1, . Location in patent: Page/Page column 8-9.
[4] Patent: EP3124482, 2017, A1, . Location in patent: Paragraph 0211; 0213.
[5] Patent: WO2007/50612, 2007, A1, . Location in patent: Page/Page column 116-117.
[6] Patent: WO2009/156100, 2009, A1, . Location in patent: Page/Page column 156.
  • 2
  • [ 112497-89-9 ]
  • [ 34916-10-4 ]
References: [1] Patent: US2007/149562, 2007, A1, . Location in patent: Page/Page column 36.
  • 3
  • [ 100-45-8 ]
  • [ 34916-10-4 ]
  • [ 17983-30-1 ]
References: [1] Patent: WO2010/54988, 2010, A2, . Location in patent: Page/Page column 26-27.
  • 4
  • [ 143-33-9 ]
  • [ 108-94-1 ]
  • [ 34916-10-4 ]
References: [1] Tetrahedron Letters, 1986, vol. 27, # 35, p. 4215 - 4216.
[2] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1986, vol. 35, # 3, p. 671 - 672[3] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1986, # 3, p. 729 - 730.
  • 5
  • [ 143-33-9 ]
  • [ 108-94-1 ]
  • [ 931-97-5 ]
  • [ 34916-10-4 ]
References: [1] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1986, vol. 35, # 12, p. 2499 - 2506[2] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1986, # 12, p. 2725 - 2734.
  • 6
  • [ 4746-97-8 ]
  • [ 34916-10-4 ]
References: [1] Patent: EP3124482, 2017, A1, .
[2] Patent: WO2018/229139, 2018, A1, .
  • 7
  • [ 58774-05-3 ]
  • [ 34916-10-4 ]
References: [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1975, p. 1885 - 1888.
  • 8
  • [ 34916-10-4 ]
  • [ 24056-34-6 ]
YieldReaction ConditionsOperation in experiment
99% at 0 - 20℃; for 1 h; Inert atmosphere Into a 250-mL 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed 119.1 (10 g, 81.20 mmol, 1.00 equiv), methanol (100 mL). This was followed by the addition of NaBH4 (1.52 g, 40.18 mmol, 0.50 equiv) at 0° C. in a water/ice bath. The resulting solution was stirred for 1 h at room temperature. The reaction was then quenched by the addition of 20 mL of NH4Cl (aq). The resulting solution was extracted with 2×100 mL of ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum. This resulted in 10.02 g (99percent) of 119.2 as colorless oil.
References: [1] Patent: US2017/166584, 2017, A1, . Location in patent: Paragraph 0887-0889.
[2] Annales de Chimie (Cachan, France), 1955, vol. &lt;12&gt; 10, p. 497,531.
[3] Bulletin de la Societe Chimique de France, 1954, p. 610,612.
[4] Patent: WO2009/156100, 2009, A1, . Location in patent: Page/Page column 156.
 

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