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Chemical Structure| 1072-72-6 Chemical Structure| 1072-72-6

Structure of Tetrahydrothiopyran-4-one
CAS No.: 1072-72-6

Chemical Structure| 1072-72-6

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Product Details of [ 1072-72-6 ]

CAS No. :1072-72-6
Formula : C5H8OS
M.W : 116.18
SMILES Code : O=C1CCSCC1
MDL No. :MFCD00006660
InChI Key :OVRJVKCZJCNSOW-UHFFFAOYSA-N
Pubchem ID :66173

Safety of [ 1072-72-6 ]

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

Computational Chemistry of [ 1072-72-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 7
Num. arom. heavy atoms 0
Fraction Csp3 0.8
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 31.83
TPSA ?

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

42.37 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.33
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

0.33
Log Po/w (WLOGP)?

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

1.08
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.

0.62
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

2.2
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.11

Water Solubility

Log S (ESOL):?

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

-0.77
Solubility 19.8 mg/ml ; 0.171 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.

-0.78
Solubility 19.1 mg/ml ; 0.165 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

-1.21
Solubility 7.11 mg/ml ; 0.0612 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.

-6.77 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)

2.25

Application In Synthesis of [ 1072-72-6 ]

* 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 [ 1072-72-6 ]

[ 1072-72-6 ] Synthesis Path-Downstream   1~8

  • 1
  • [ 1072-72-6 ]
  • [ 2896-98-2 ]
YieldReaction ConditionsOperation in experiment
62% To a mixture of tetrahydrothiopyran-4-one (5.14 g) and conc. hydrochloric acid (20 mL) was added sodium azide (4.31 g) under ice-cooling. The reaction mixture was stirred at room temperature for 4 hrs., and sodium carbonate was added. The mixture was diluted with iced water and extracted with chloroform. The organic layer was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated to give 1,4-thiazepan-5-one as crystals (3.62 g, yield 62%). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 120-121C.
(Ref: J. Org. Chem. 1960, 25, 1953-1956.) To a stirred solution of tetrahydrothiopyran-4-one 1 (10 g, 86 mmol) in cone. HCl (43 mL) cooled to 0 0C is added sodium azide (8.4 g, 129 mmol) portionwise over 30-60 min, (note: gas evolution). When the addition is complete the reaction mixture is stirred at RT for 4 h.The mixture is cooled to 0 0C and solid Na2CO3 is added portionwise (note: gas evolution), plus water to dissolve the salts, until the solution is alkaline ~pH 9. The alkaline solution is diluted with DCM (200 mL), the phases are seperated and the aqueous layer is extracted with DCM (3 x 100 mL). The combined organic layers are EPO <DP n="24"/>dried over MgSOphi filtered and concentrated to a low volume (-20 mL), petroleum ether is added and the solid is collected by filtration and dried to afford the title compound as a white solid: 1H NMR (400 MHz, DMSO) delta 7.52 (s, IH), 3.39 (m, 2H), 2.63 (m, 2H), 2.58 (m, 4H); MS-APCI (m/z+-) 131.9 (M+H).
  • 2
  • [ 1072-72-6 ]
  • [ 6296-99-7 ]
  • [ 111205-69-7 ]
YieldReaction ConditionsOperation in experiment
With toluene-4-sulfonic acid; In ethyl acetate; toluene; (a) To a solution of 15 g of 4H-tetrahydrothiopyran-4-one in 500 mL of toluene, 25 g of <strong>[6296-99-7]diethyl aminomethylenemalonate</strong> and 0.8 of p-toluenesulfonic acid are added. The resultant mixture is refluxed for 48 hours with a water separator under nitrogen atmosphere, then evaporated to dryness. The dried residue is purified by flash chromatography on a silica gel column, using toluene and 5percent ethyl acetate in toluene as eluents to obtain the desired product, diethyl N-(2H-5,6-dihydrothiopyran-4-yl)aminomethylenemalonate.
With toluene-4-sulfonic acid; In ethyl acetate; toluene; (a) To a solution of 15 g of 4H-tetrahydrothiopyran-4-one in 500 mL of toluene, 25 g of <strong>[6296-99-7]diethyl aminomethylenemalonate</strong> and 0.8 g of p-toluenesulfonic acid are added. The resultant mixture is refluxed for 48 hours with a water separator under nitrogen atmosphere, then evaporated to dryness. The dried residue is purified by flash chromatography on a silica gel column, using toluene and 5percent ethyl acetate in toluene as eluents to obtain the desired product, diethyl N-(2H-5,6-dihydrothiopyran-4-yl)-aminomethylenemalonate.
With toluene-4-sulfonic acid; In ethyl acetate; toluene; (a) To a solution of 15 g of 4H-tetrahydrothiopyran-4-one in 500 mL of toluene, 25 g of <strong>[6296-99-7]diethyl aminomethylenemalonate</strong> and 0.8 g of p-toluenesulfonic acid are added. The resultant mixture is refluxed for 48 hours with a water separator under nitrogen atmosphere, then evaporated to dryness. The dried residue is purified by flash chromatography on a silica gel column, using toluene and 5percent ethyl acetate in toluene as eluents to obtain the desired product, diethyl N-(2H-5,6-dihydrothiopyran-4-yl)aminomethylenemalonate.
  • 3
  • [ 1072-72-6 ]
  • [ 194152-05-1 ]
  • 5
  • [ 1072-72-6 ]
  • [ 2896-98-2 ]
  • [ 101184-85-4 ]
YieldReaction ConditionsOperation in experiment
4.30 g (81%) With sodium carbonate; In hydrogenchloride; water; Preparation 34 1,4-Thiazepane To a stirred solution of tetrahydrothiopyran-4-one (4.74 g) in conc. HCl (20.7 mL) cooled to 0 C. is added portion-wise sodium azide (3.98 g, 61.2 mmol). After addition is complete, the reaction is stirred at room temperature for 4 h. Solid sodium carbonate is then added portion-wise until the solution was slightly alkaline (pH=9). Water is added during addition of sodium carbonate to dissolve the salt. The alkaline solution is diluted with CHCl3 (125 mL), and the phases are separated. The aqueous layer is extracted with CHCl3 (2*75 mL). The combined organic layers are dried (Na2SO4), filtered, and concentrated. The crude product is recrystallized from CH2Cl2/hexanes to afford 4.30 g (81%) of 1,4-thiazepan-5-one as a white solid. Physical characteristics are as follows: Mp 114-116 C.; 1H NMR (300 MHz, CDCl3) delta6.41, 3.66, 2.96, 2.76.
  • 6
  • [ 1072-72-6 ]
  • [ 131818-17-2 ]
  • [ 1009083-69-5 ]
YieldReaction ConditionsOperation in experiment
92% A solution of 4-bromo-N-Boc aniline (6.0 g, 22.1 mmol) in THF (100 ml) at -78 0C under nitrogen was added n-butyllithium (1.6 M in hexane, 34.4 ml, 55 mmol) dropwise over 20 min. The resulting yellow solution was stirred at -78 0C for 30 min and was then treated with a solution of tetrahydrothiopyran-4-one (2.82 g, 24.3 mmol) in THF (25 mi_). The reaction mixture was stirred for 4 hrs, during which the reaction temperature was allowed to rise to 0 0C. The eraction was quenched with saturated aqueous ammonium chloride (25 ml). The mixture was then diluted with water (25 ml) and Et2O (25 ml). The layers were separated, and the organic phase was washed with brine (10 ml), dried over Na2SO4, and concentrated in vacuo. The residue was flushed through a plug of silica gel with EtOAc: Heptane (1:1) to afford tert-butyl 4-(4-hydroxy-tetrahydro-2H-thiopyran-4-yl)phenylcarbamate (6.2 gram, 92%) as a white solid. 1H NMR (400 MHz1 d-CDCI3) delta 7.30 - 7.41 (m, 4 H) 6.44 (br. s., 1 H) 3.13 - 3.24 (m, 2 H) 2.41 - 2.50 (m, 2 H) 2.09 - 2.19 (m, 2 H) 1.95 - 2.03 (m, 2 H) 1.50 (s, 9 H)
  • 7
  • [ 1072-72-6 ]
  • [ 14150-94-8 ]
  • [ 214699-38-4 ]
  • 8
  • [ 1072-72-6 ]
  • [ 1065181-58-9 ]
  • [ 1065181-66-9 ]
YieldReaction ConditionsOperation in experiment
76% The title compound can also be prepared according to the following procedure: TMSOTf (1.4 ml_, 7.7 mmol) was added dropwise to a solution of tetrahydro-4H-thiopyran- 4-one (0.88 g, 7.6 mmol) in DCM (80 ml.) in the presence of molecular sieves at 0 0C (bath temp). A solution of ethyl 5-bromo-1 /-/-indole-7-carboxylate (2 g, 7.4 mmol). in DCM (20 ml.) was added and the reaction was stirred for 15 min. Triethylsilane (2 ml_, 12.5 mmol) was added and the reaction was allowed to warm to room temperature overnight. Saturated aqueous Na2CO3 was added, the layers separated and the aqueous layer extracted with DCM. The combined organic layers were dried (Na2SO4) and concentrated under reduced pressure. The residue was washed with MeOH and dried in a vacuum oven, giving 2.07 g (76%) of the title compound.
 

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