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Structure of 1696-20-4

Chemical Structure| 1696-20-4

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Product Details of [ 1696-20-4 ]

CAS No. :1696-20-4
Formula : C6H11NO2
M.W : 129.16
SMILES Code : CC(=O)N1CCOCC1
MDL No. :MFCD00006171
InChI Key :KYWXRBNOYGGPIZ-UHFFFAOYSA-N
Pubchem ID :15543

Safety of [ 1696-20-4 ]

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

Computational Chemistry of [ 1696-20-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 0
Fraction Csp3 0.83
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 36.94
TPSA ?

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

29.54 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

-1.22
Log Po/w (WLOGP)?

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

-0.52
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.

-0.41
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

0.67
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.02

Water Solubility

Log S (ESOL):?

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

0.19
Solubility 202.0 mg/ml ; 1.56 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Highly soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

1.09
Solubility 1610.0 mg/ml ; 12.4 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Highly 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

-0.36
Solubility 56.0 mg/ml ; 0.434 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

Low
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.

-7.95 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)

1.34

Application In Synthesis of [ 1696-20-4 ]

* 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.

  • Downstream synthetic route of [ 1696-20-4 ]

[ 1696-20-4 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 1696-20-4 ]
  • [ 22717-55-1 ]
  • 1-(4-Chloro-2-hydroxy-phenyl)-3-morpholin-4-yl-propane-1,3-dione [ No CAS ]
  • 2
  • [ 1696-20-4 ]
  • [ 4175-77-3 ]
  • [ 208264-53-3 ]
YieldReaction ConditionsOperation in experiment
79.5% A solution of 2,4-dibromothiazole B.31 (5.0128 g, 20.63 mmol) in ether (52 mL) was cooled to -78 0C. To the cooled solution was added n-BuLi (1.6 M sol. in hexane, 14.2 mL, 22.72 mmol) and the mixture was stirred at -78 0C for 30 minutes. To the cooled mixture was then added dropwise N-acetylmorpholine (3.1 mL, 26.83 mmol). The mixture was stirred at -78 0C for 1.5 hours and then room temperature for 18 hours. The mixture was diluted with ether (200 mL), washed with saturated aqueous NaHCO3 (100 mL x 1), dried over MgSO4, filtered, and concentrated under reduced pressure. The product was purified by silica gel column chromatography using 0% to 50% gradient of ethyl acetate in hexane as eluent to give 1 -(4- bromothiazol-2-yl)ethanone B.32 (3.383 g, 79.5% yield): 1H NMR (500 MHz, CHLOROFORM-d) 5 ppm 7.59 (1 H, s), 2.73 (3 H, s); Mass Spectrum (ESI) m/e = 205.9 [M+l (79Br)] and 207.9 [M+l (81Br)].
50% To a solution of compound 21-2 (3.0 g, 12.35 mmol) in THF (25 ml) was added dropwise n-BuLi (2.5 M in hexane, 2.5 ml) at -78 C. After addition, the reaction mixture was stirred at -78 C for 30 min. N-acetyl morpholine (1.9 ml, 16.06 mmol) was added dropwise during 15 min at -78 C. After addition, the reaction mixture was stirred at -78 C for 4 h, quenched with saturated NaHCO3 (15 ml) and extracted with ethyl acetate (25 ml x 4). The combined organic layers were washed with brine (30 ml), dried over Na2SO4, filtered, concentrated and purified by silica gel column chromatography (PE : EA = 50 : 1 to 10 : 1) to afford 21-3 as a white solid (1.28 g, yield 50%).
50% Compound 22-3 (0435) To a solution of compound 22-2 (3.0 g, 12.35 mmol) in THF (25 mL) was added dropwise n-BuLi (2.5 M in hexane, 2.5 mL) at -78 C. After addition, the reaction mixture was stirred at -78 C. for 30 min. N-acetyl morpholine (1.9 mL, 16.06 mmol) was added dropwise during 15 min at -78 C. After addition, the reaction mixture was stirred at -78 C. for 4 h, then quenched with sat. NaHCO3 (15 mL) and extracted with ethyl acetate (25 mL×4). The combined organic layers were washed with brine (30 mL), dried over Na2SO4, filtered, concentrated and purified by silica gel column chromatography (PE:EA=50:1 to 10:1) to afford 22-3-3 as a white solid (1.28 g, yield 50%).
33% To a stirring solution of 2, 4-dibromothiazole 84 (50 g, 205.82 mmol) in anhydrous THF (500 mL) under inert atmosphere was added n-butyllithium (193 mL, 308.74 mmol) dropwise for 30 min at -40 oC and stirred for 1 h at the same temperature. To this was added 1- morpholinoethan-1-one (32 g, 248 mmol) in anhydrous THF (100 mL) dropwise for 20 min at -40 oC and stirred for 3 h. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was quenched with saturated ammonium chloride solution and extracted using EtOAc. The combined organic extracts were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to obtain the crude. The crude was purified through silica gel column chromatography using 1-2% EtOAc/ hexanes to afford compound 85 (14 g, 33%) as an off-white solid. TLC: 10% EtOAc/ hexanes (Rf: 0.8); 1H NMR (DMSO-d6, 400 MHz): delta 8.33 (s, 1H), 2.62 (s, 3H); LCMS Calculated for C5H4BrNOS: 204.92; LCMS observed: 208.0 (M+2)+.

  • 3
  • [ 1696-20-4 ]
  • [ 40299-87-4 ]
 

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Technical Information

Categories

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