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Chemical Structure| 22428-87-1 Chemical Structure| 22428-87-1

Structure of 22428-87-1

Chemical Structure| 22428-87-1

1,4-Dioxaspiro[4.5]decan-8-ol

CAS No.: 22428-87-1

4.5 *For Research Use Only !

Cat. No.: A130001 Purity: 98%

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Product Details of [ 22428-87-1 ]

CAS No. :22428-87-1
Formula : C8H14O3
M.W : 158.20
SMILES Code : OC(CC1)CCC21OCCO2
MDL No. :MFCD00067003
InChI Key :HKQTYQDNCKMNHZ-UHFFFAOYSA-N
Pubchem ID :567352

Safety of [ 22428-87-1 ]

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

Computational Chemistry of [ 22428-87-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 0
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 39.71
TPSA ?

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

38.69 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.0
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

0.27
Log Po/w (WLOGP)?

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

0.66
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.

0.43
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

1.36
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.94

Water Solubility

Log S (ESOL):?

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

-0.99
Solubility 16.2 mg/ml ; 0.102 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.

-0.64
Solubility 35.9 mg/ml ; 0.227 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

-0.75
Solubility 28.2 mg/ml ; 0.178 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

Yes
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.

-7.07 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)

2.99

Application In Synthesis of [ 22428-87-1 ]

* 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 [ 22428-87-1 ]

[ 22428-87-1 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 22428-87-1 ]
  • [ 7651-82-3 ]
  • [ 1041423-19-1 ]
YieldReaction ConditionsOperation in experiment
4-(lsoquinolin-6-yloxy)-cyc.ohexanone (27); A suspension of 9 g triphenylphosphine (bound to polystyrene, Argonaut, 1.6 mmol/g, 14.4 mmol) and 1.57 ml_ (1.74 g, 10 mmol) diethyl azocarboxylate in 100 mL dichloromethane was stirred for 10 min under argon atmosphere. Then 1.45 g (10 mmol) <strong>[7651-82-3]6-hydroxy-isoquinoline</strong> and 1.58 g (10 mmol) 1 ,4-dioxa-spiro[4.5]decan-8-ol were added. After 40 min 1.39 mL (1 g, 10 mmol) triethyl amine was added and the reaction was allowed to shake for 16 h at room temperature. After filtration the organic layer was extracted with 1 N NaOH, dried over Na2SO4, filtered and concentrated in vacuo.The crude material (2.2 g) was dissolved in 200 mL acetone and 10 mL water. 1.5 g (7.9 mmol) of para-toluene sulfonic acid were added and the reaction was heated to reflux temperature for 6 h. Then the solvents were distilled off. The remainder was dissolved in dichloromethane and was extracted with aqueous Na2CO3 solution. After drying over Na2SO4, filtration and removal of the solvents the crude product was purified by flash chromatography to yield 1.19 g of 27 as a white solid. 1H-NMR (de-DMSO): delta = 9.16 (1 H, s), 8.41 (1 H, d, J = 5.8 Hz), 8.05 (1 H, d, J = 8.9 Hz), 7.70 (1 H, d, J = 5.8 Hz), 7.51 (1 H, d, J = 2.5 Hz), 7.36 (1 H, dd, J = 8.9 und 2.5 Hz), 5.04 (1 H, m), 2.44 (4H, m), 2.22 (2H, m), 2.11 (2H, m). MS: m/z = 242 (MH+).
  • 3
  • [ 22428-87-1 ]
  • [ 4983-28-2 ]
  • [ 1314391-25-7 ]
YieldReaction ConditionsOperation in experiment
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 20℃; 2-Chloropyrimidin-5-ol (Intermediate No.86 Step 2, 200 mg,. 1.5 mmol) was dissolved in THF (5 mL) and triphenylphosphine (600 mg, 23 mmol) and 1,4-dioxa- spiro[4.5]decan-8-ol (365 mg, 2.30 mmol) was added, followed by DIAD (0.45 mL, 2.3 mmol). The reaction mixture was stirred at ambient temperature overnight. The reaction mixture was diluted with EtOAc, washed with saturated NaHC03> and the aqueous phase was extracted with. EtOAc. The combined organic extracts were dried over Na2S04, filtered, dry loaded onto silica gel and the cpade residue was purified by flash chromatography (MPLC, 2-20percentDCM-hexane followed-by 5-60percent EtOAc-hexane) to give a crude residue which was further purified by reverse phase preparative HPLC (0-80percent MeCN-H20, 0.05percent TFA). Fractions containing the pure compound were collected and the free base was liberated by an EtOAc extraction and sat.NaHC03 wash to give 2-c oro-5-(l ,4-dioxaspiro[4.5]dec-8-yloxy)pyrimidine as a solid.LRMS (ESI) calc'd for C12H16C1N203 [M+H] +: 271 , Found: 271
  • 4
  • [ 22428-87-1 ]
  • [ 163622-50-2 ]
  • [ 330792-72-8 ]
  • 5
  • [ 22428-87-1 ]
  • [ 163622-50-2 ]
  • [ 943974-70-7 ]
YieldReaction ConditionsOperation in experiment
60% 5-Iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine (1.34 g, 5.15 mmol),4-Hydroxycyclohexanone ethylene glycol acetal (1.22 g, 7.7 mmol) and triphenylphosphine (4.05 g, 15.45 mmol) were added to 30 mL of anhydrous tetrahydrofuran.Under nitrogen atmosphere, diisopropyl azodicarboxylate (2.1 g, 10.3 mmol) was slowly added dropwise under ice-cooling, and the mixture was allowed to react to room temperature overnight.The reaction was completely detected by TLC, and the solvent was evaporated in vacuo.The mixture was stirred at room temperature for 0.5 hour, filtered, and the filter cake was rinsed with 5 mL of ethyl acetate and dried to give 1.5 g of a white solid, which was dissolved in 20 mL of acetone, and 6 M hydrochloric acid was slowly added dropwise to pH = 3 in an ice bath, and the reaction mixture was reacted at room temperature for 3 hours. . Rotate the solvent,Add ethyl acetate to dissolve,Wash with saturated sodium bicarbonate solution, dry,Concentrated to a white solid, 1.1 g, yield 60%.
 

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Technical Information

Categories

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