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Chemical Structure| 7218-43-1 Chemical Structure| 7218-43-1

Structure of Propargyl-PEG2-OH
CAS No.: 7218-43-1

Chemical Structure| 7218-43-1

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Product Details of [ 7218-43-1 ]

CAS No. :7218-43-1
Formula : C7H12O3
M.W : 144.17
SMILES Code : C#CCOCCOCCO
MDL No. :MFCD00053353
InChI Key :HUSDTFBXUYBZJD-UHFFFAOYSA-N
Pubchem ID :81639

Safety of [ 7218-43-1 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H227-H315-H319
Precautionary Statements:P210-P264-P280-P302+P352+P332+P313+P362+P364-P305+P351+P338+P337+P313-P370+P378-P403+P235-P501

Computational Chemistry of [ 7218-43-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 0
Fraction Csp3 0.71
Num. rotatable bonds 6
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 37.26
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.

2.12
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

-0.64
Log Po/w (WLOGP)?

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

-0.28
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.

-0.07
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

0.81
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.39

Water Solubility

Log S (ESOL):?

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

0.07
Solubility 168.0 mg/ml ; 1.16 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.

0.3
Solubility 288.0 mg/ml ; 2.0 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

-0.87
Solubility 19.5 mg/ml ; 0.135 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.

-7.63 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

1.0 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)

3.19

Application In Synthesis of [ 7218-43-1 ]

* 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 [ 7218-43-1 ]

[ 7218-43-1 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 7218-43-1 ]
  • [ 98-59-9 ]
  • [ 1119249-30-7 ]
YieldReaction ConditionsOperation in experiment
90% General procedure: In an oven dried REF, monopropargylate (1.0 eq)was dissolved with stirring in TRF at 0 C. Aqueous KOR (4 eq) was added to the flask in small portions immediately. After 10 minutes, tosyl chloride (1.2 eq) solution in TRF was added dropwise and stirred for 12 hours. Upon completion, reaction was quenched with aqueous ammonium chloride and extracted with DCM thrice to get crude product which was purified using silica gel column chromatography using MeORDCM as eluent. The compound 9b was prepared by general procedure 4.1.2, starting from 9a (1 g, 7 mmol), tosyl chloride (1.5 g, 8 mmol), potassium hydroxide (1.3 g, 24 mmol) in THF. The product was obtained as a pale yellow liquid (1.8 g, 6 mmol, 90%) afier purification by silica gel column chromatography using ethyl acetate/hexane as eluent, RrO.55 in 50% ethyl acetate/hexane. ‘H NMR (400 MHz, COd3): OH7.78 (d, J=8 Hz, 2H), 7.32 (d, J=8 Hz, 2H), 4.17-4.13 (m, 4H), 3.70-3.58 (m, 6H), 2.44-2.41 (m, 4H). ‘3C NMR (100 MHz, CDC13): O 144.92, 132.94,129.91, 128.04, 79.57, 77.16, 74.73, 70.59, 69.30, 69.05,68.73, 60.45, 58.48, 21.71, 21.12, 14.31. HRMS (M+Na): 321.07Mol. formula: C,4H,8055Mol. Weight: 298.08Physical appearance: pale yellow liquidYield: 90%
87% With sodium hydroxide; In tetrahydrofuran; at 0 - 20℃; A solution of S3i (1.9 g, 13 mmol) in THF (30 mL) was treated with powdered sodium hydroxide (0.68 g, 17 mmol) at 0 C and toluene sulfonyl chloride (2.7 g, 14 mmol) was added. The reaction mixture was stirred allowing it to warm to room temperature overnight. The solvent was evaporated and the residue taken up in dichloromethane and washed twice with water. After drying over magnesium sulphate the solvent was evaporated and the tosylate purified by chromatography (hexane / ethyl acetate 7:1) to provide a yellow liquid (3.4 g, 87%). The intermediate (3.0 g, 10 mmol) was dissolved in acetone (40 mL) and treated with sodium iodide (3.0 g, 20 mmol). After stirring at room temperature overnight, the solvent was evaporated and the residue taken up in dichloromethane and water. The organic phase was washed with aqueoussodium thiosulfate solution and water and dried over magnesium sulfate. Concentration furnished 9-iodo-4,7-dioxa-nonyne S3 (2.2 g, 88%) as colourless liquid. 1H NMR (400 MHz, CDCI3): O 4.23 (5, 2H), 3.77 (t, 2H), 3.71 (bs, 4H), 3.28 (t, 2H), 2.45 (bs, 1H); 13C NMR (100 MHz, CDCI3): O 79.51, 74.61, 71.98,70.00, 69.05, 58.47, 2.67.
82% With dmap; triethylamine; In dichloromethane; at 0 - 25℃; for 16h; To a solution of 2-(2-prop-2-ynoxyethoxy)ethanol (2.00 g, 13.8 mmol, Intermediate LC), TEA (4.21 g, 41.6 mmol) and DMAP (170 mg, 1.39 mmol) in DCM (60 mL) was added 4-methylbenzenesulfonyl chloride (5.29 g, 27.7 mmol) at 0 C. The mixture was then stirred at 25 C. for 16 hours. On completion, the mixture was washed with 2.0 M aq.HCl (20 mL) and brine (20 mL), dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel to give the title compound (3.40 g, 82% yield) as light yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.81 (d, J=8.4 Hz, 2H), 7.35 (m, J=8.0 Hz, 2H), 4.23-4.14 (m, 4H), 3.73-3.68 (m, 2H), 3.67-3.59 (m, 4H), 2.46 (s, 3H), 2.44 (t, J=2.4 Hz, 1H).
68% With triethylamine; In dichloromethane; at 20℃; Into a 250-mL round-bottom flask, was placed a solution of 2-[2-(prop-2-yn-1-yloxy)ethoxy]ethan-1-ol (1 g, 6.94 mmol, 1.00 equiv) in dichloromethane (80 mL), triethylamine (2.8 g, 27.67 mmol, 3.00 equiv), 4-dimethylaminopyridine (270 mg, 2.21 mmol, 0.30 equiv), and 4-toluenesulfonyl chloride (1.9 g, 9.97 mmol, 1.50 equiv). The resulting solution was stirred for 12 hours at room temperature. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column eluting with ethyl acetate/petroleum ether (1:2). The collected fractions were combined and concentrated under vacuum. This resulted in 1.4 g (68%) of 2-[2-(prop-2-yn-1-yloxy)ethoxy]ethyl 4-methylbenzene-1-sulfonate as yellow oil.

  • 2
  • [ 7218-43-1 ]
  • [ 133-59-5 ]
  • [ 1119249-30-7 ]
YieldReaction ConditionsOperation in experiment
1.7 g (68%) Example 12 3,6-dioxanon-8-yn-1-yl p-toluenesulfonate (12, propargyl-PEG2-OTs) 3,6-Dioxanon-8-yn-1-ol 11 (1.2 g, 8.3 mmol) and toluenesulfonyl chloride were reacted according to Example 3 to yield 1.7 g (68%) of 12 as a colorless oil. 1H NMR (400 MHz, CDCl3): δ 2.44 (t, J=2.4 Hz, 1H), 2.45 (s, 3H), 3.60-3.65 (m. 4H), 3.70 (t, J=4.8 Hz, 2H), 4.15-4.18 (m, 4H), 7.35 (d, J=8.0 Hz, 2H), 7.80 (d, J=8 Hz, 2H); 13C NMR (100.6 MHz, CDCl3): δ 21.6, 58.4, 68.7, 69.0, 69.2, 70.6, 74.6, 79.5, 128.0, 129.8, 133.1, 144.8; MS ESI (m/z): [M+H]+ calcd. for C14H19O5S, 299.09; found 299.1.
 

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