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Chemical Structure| 177760-04-2

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Product Details of [ 177760-04-2 ]

CAS No. :177760-04-2
Formula : C7H11N3O2
M.W : 169.18
SMILES Code : O=C(C1=CN=C(N)N1C)OCC
MDL No. :MFCD09997799
InChI Key :CXSLXRSUUJLZBT-UHFFFAOYSA-N
Pubchem ID :21503744

Safety of [ 177760-04-2 ]

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

Computational Chemistry of [ 177760-04-2 ] 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.

1.58
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

0.22
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.

-0.23
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

0.31

Water Solubility

Log S (ESOL):?

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

-1.14
Solubility 12.3 mg/ml ; 0.0728 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.

-1.25
Solubility 9.46 mg/ml ; 0.0559 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.

-7.18 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)

2.05

Application In Synthesis of [ 177760-04-2 ]

* 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.

  • Upstream synthesis route of [ 177760-04-2 ]

[ 177760-04-2 ] Synthesis Path-Upstream   1~6

  • 1
  • [ 89531-66-8 ]
  • [ 177760-04-2 ]
YieldReaction ConditionsOperation in experiment
61%
Stage #1: With sodium hydride; formic acid ethyl ester; sodium nitrite In tetrahydrofuran; cyclohexane; mineral oil at 20℃; for 3.5 h;
Stage #2: With hydrogenchloride In ethanol; water at 110℃; for 2 h;
Stage #3: With CYANAMID; sodium hydroxide In ethanol; water for 1.5 h; Reflux
To a solution of N-formyl sarcosine ethyl ester (3) (29.6 g,204 mmol) in an equal mixture of ethyl formate and THF (190 mL)with cyclohexane (12 mL), was added slowly NaH (60percent wt inmineral oil, 12.5 g, 313 mmol) at room temperature. After the addition was completed and hydrogen release stopped, the reaction mixture was allowed to stirred during 3.5 h. The reaction mixture was concentrated under vacuum. The obtained solid was suspended in a solution of EtOH (250 mL) containing concentrated aq.HCl 32percent (61 mL) and refluxed for 2 h. The hot reaction mixture was filtered and the resulting colourless solid was washed with boilingEtOH (2 150 mL). The filtrate was concentrated under vacuum and diluted with a mixture of EtOH/water (500 mL, 70/30, v/v). The pH of the solution was adjusted to 3, using an aqueous 5M solution of NaOH and cyanamide (17.5 g, 416 mmol) was added. The resulting mixture was refluxed for 1.5 h, then cooled to rt and concentrated under reduced pressure to approximately 1/8 of the initial volume. The pH of the remaining solution was adjusted to 9-10 with a saturated aqueous solution of potassium carbonate, after cooling in an ice-water bath. The precipitate formed was removed by filtration, washed with water (2 10 mL) and dried under vacuum at 40 °C overnight to afford compound 4 (16.9 g,99.9 mmol) as a pale yellow to orange solid. A supplementary fraction can be yielded after extraction of the remaining filtrate with ethyl acetate (3 100 mL). The combined organic layers weredried over MgSO4, filtered and evaporated under reduced pressure.The residue was purified by column chromatography on silica gelusing ethyl acetate/ethanol (95/5, v/v with 1percent NH4OH) as eluent to yield compound 4 (3.78 g, 22.3 mmol). Yield 61percent; Rf 0.33 (SiO2,EtOAc/EtOH, 9/1, v/v); mp 131 C (Lit [40]. mp 130-133 °C); IR(ATR) n cm1 3390, 3119, 1647, 1542, 1168, 750, 737; 1H NMR(CDCl3, 400 MHz) δ 7.39 (s, 1H, CHAr), 4.66 (br.s, 2H, NH2), 4.25 (q,2H, 3J 7.1 Hz, CH2CH3), 3.65 (s, 3H, NCH3), 1.32 (t, 3H, 3J 7.1 Hz,CH2CH3); 13C NMR (DMSO‑d6, 126 MHz) δ 159.68 (CO), 154.27(CArNH2), 136.02 (CHAr), 116.88 (CArCO), 58.82 (OCH2), 30.17 (NCH3),14.30 (CH2CH3).
References: [1] European Journal of Medicinal Chemistry, 2018, vol. 158, p. 51 - 67.
  • 2
  • [ 3154-51-6 ]
  • [ 107-31-3 ]
  • [ 177760-04-2 ]
References: [1] Patent: WO2014/18807, 2014, A1, . Location in patent: Paragraph 00299; 00300.
  • 3
  • [ 420-04-2 ]
  • [ 177760-04-2 ]
References: [1] Patent: WO2015/51921, 2015, A1, . Location in patent: Page/Page column 37; 38.
  • 4
  • [ 420-04-2 ]
  • [ 177760-04-2 ]
YieldReaction ConditionsOperation in experiment
1.97 g With sodium hydroxide In ethanol; water at 100℃; for 1.5 h; Inert atmosphere To a suspension of sarcosine ethyl ester (4.00 g, 0.026 mol) in THF (90 mL) and ethyl formate (90 mL) was added NaH (60 percent dispersion in mineral oil, 10.0 g, 0.25 mol) in several portions at room temperature. The reaction mixture was stirred for 3 h, and, during this time, a yellow suspension formed. The reaction mixture was concentrated and triturated with hexane (2 x 150 mL). The hexane was decanted, and the resulting light tan solid was dried in vacuo. Ethanol (80 mL) and concentrated aqueous HCl (16 mL) were added to the solid, and the suspension was heated to reflux for 2 h. The reaction mixture was then filtered while hot, and the filter was rinsed with boiling ethanol (2 x 50 mL). The combined filtrate was concentrated to yield a brown oil. The oil was diluted with ethanol (140 mL) and water (60 mL), and the pH of the solution was adjusted to 3 by using NaOH solution (2 M). Cyanamide (2.18 g, 0.052 mol) was added, and the resulting solution was heated to reflux for 1.5 h. After being cooled to room temperature, the reaction mixture was concentrated to approximately 1/8 of its original volume. Solid K2CO3 was added to adjust the pH of the concentrated reaction mixture to 8-9, resulting in the formation of a yellow precipitate. The solid was removed by filtration, washed with a K2CO3 solution (1 M, 1 x 20 mL) and water (2 x 20 mL) and dried to afford a pale yellow solid (1.97 g, 12.0 mmol, 45percent). 1H NMR (600 MHz, CDCl3) δ 7.45 (1H, s), 4.27 (2H, q, J = 7.1 Hz), 4.25 (2H, s), 3.68 (3H, s), 1.34 (3H, t, J = 7.1 Hz).13C NMR (151 MHz, CDCl3) δ 160.67, 151.89, 135.50, 119.05, 59.82, 30.55, 14.41.
References: [1] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 3, p. 636 - 641.
  • 5
  • [ 420-04-2 ]
  • [ 107-31-3 ]
  • [ 52605-49-9 ]
  • [ 177760-04-2 ]
References: [1] Patent: US5843942, 1998, A, .
  • 6
  • [ 420-04-2 ]
  • [ 177760-04-2 ]
References: [1] Patent: WO2007/2931, 2007, A2, . Location in patent: Page/Page column 140.
[2] Patent: WO2007/2931, 2007, A2, . Location in patent: Page/Page column 141.
 

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