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Chemical Structure| 2695-47-8 Chemical Structure| 2695-47-8

Structure of 2695-47-8

Chemical Structure| 2695-47-8

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Product Details of [ 2695-47-8 ]

CAS No. :2695-47-8
Formula : C6H11Br
M.W : 163.06
SMILES Code : C=CCCCCBr
MDL No. :MFCD00000269
InChI Key :RIMXEJYJXDBLIE-UHFFFAOYSA-N
Pubchem ID :75906

Safety of [ 2695-47-8 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H226-H315-H319-H335-H360
Precautionary Statements:P201-P202-P210-P233-P240-P241-P242-P243-P261-P264-P271-P280-P303+P361+P353-P304+P340+P312-P305+P351+P338-P308+P313-P332+P313-P337+P313-P370+P378-P403+P233-P403+P235-P405-P501
Class:3
UN#:1993
Packing Group:

Computational Chemistry of [ 2695-47-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 7
Num. arom. heavy atoms 0
Fraction Csp3 0.67
Num. rotatable bonds 4
Num. H-bond acceptors 0.0
Num. H-bond donors 0.0
Molar Refractivity 38.35
TPSA ?

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

0.0 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.46
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

2.81
Log Po/w (WLOGP)?

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

2.74
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.

2.98
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

2.43
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.68

Water Solubility

Log S (ESOL):?

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

-2.36
Solubility 0.716 mg/ml ; 0.00439 mol/l
Class?

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

Soluble
Log S (Ali)?

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

-2.47
Solubility 0.556 mg/ml ; 0.00341 mol/l
Class?

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

-2.79
Solubility 0.266 mg/ml ; 0.00163 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

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.

-5.3 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

2.0
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

2.0 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)

2.63

Application In Synthesis of [ 2695-47-8 ]

* 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 [ 2695-47-8 ]

[ 2695-47-8 ] Synthesis Path-Downstream   1~7

  • 1
  • [ 4877-80-9 ]
  • [ 2695-47-8 ]
  • C54H72O6 [ No CAS ]
  • C60H82O6 [ No CAS ]
  • 2
  • [ 403-01-0 ]
  • [ 2695-47-8 ]
  • [ 1345002-88-1 ]
  • 3
  • [ 102831-44-7 ]
  • [ 2695-47-8 ]
  • C18H31NO6 [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: Metallic sodium (4.0 g, 165 mmol) was dissolved in absolute ethanol (165 mL) and diethyl tert butoxycarbonylaminomalonate (45.42 g, 165 mmol) was added to the solution. The reaction mixture was refluxed for 30 min for the complete removal of the labile hydrogen and then 5-bromo-1-pentene (25 g, 165 mmol) was added and refluxed for 6 h. The reaction mixture was cooled on an ice bath and hydrolysis was carried out by the treatment of 1 M aq NaOH (165 mL, 165 mmol). After selective hydrolysis for 4 h at 0 C, ethanol was evaporated and the unreacted 5-bromo-1-pentene was removed by extraction with diethyl ether under basic condition. Then the aqueous solution was extracted with ethyl acetate at pH 3-4, by adding solid citric acid. Finally, ethyl acetate layer was washed with brine and dried over anhydrous MgSO4. Ethyl acetate was evaporated to obtain a colorless oil of monoester monoacid (42.5 g, 82%). HPLC, retention time 7.55 min. It was then dissolved in toluene (180 mL) and refluxed for 3 h. The oily ester after evaporation of toluene is then subjected to silica gel column chromatographic purification to get Boc-dl-Ae7-OEt (14) as colorless oil (30.8 g, 84%). The resulting oily mass was suspended into a mixture of water (342 mL) and DMF (114 mL) (1:3, v/v) solvent system at 38 C using a mechanical stirrer and pH was adjusted at about 7-8 by adding 1 M aq ammonia solution. Then subtilisin Carlsberg from B. licheniformis (57 mg) was added and pH was maintained at 7-8 by continuous addition of 1 M aq ammonia solution. The reaction was completed within 4 h. Water and DMF were evaporated and Boc-d-Ae7-OEt (16) (15.6 g, 50.5%) was extracted with diethyl ether under basic condition. Then the aqueous solution was extracted with ethyl acetate as described above to get Boc-l-Ae7-OH (8) as colorless oil (13.6 g, 49%). HPLC, retention time 7.05 min.
  • 4
  • [ 42726-73-8 ]
  • [ 2695-47-8 ]
  • 1-(tert-butyl) 3-methyl 2-(hex-5-en-1-yl)malonate [ No CAS ]
YieldReaction ConditionsOperation in experiment
97% With tetra-(n-butyl)ammonium iodide; caesium carbonate; In acetonitrile; at 60℃;Inert atmosphere; A mixture of <strong>[42726-73-8]tert-butyl methyl malonate</strong> (5.9 g, 33.87 mmol) and 6-bromo-1-hexene (7.27 g, 42.34 mmol) in CH3CN (75 mL) was treated with cesium carbonate (16.55 g, 50.80 mmol) and tetra-n-butylammonium iodide (2.50 g, 6.77 mmol) and then heated to 60 °C overnight with stirring under nitrogen. The reaction was cooled and filtered, using EtOAc to rinse the salts. The filtrate was acidified with 1N HCl (~200 mL) and was then extracted with EtOAc (3×). The combined organic phases were dried (Na2SO4), and subjected to silica gel chromatography with a 0percent to 50percent EtOAc gradient to furnish the titled product (8.43 g, 97percent yield). 1H NMR (400 MHz, CDCl3): delta 5.75 (ddt, J = 17.0, 10.2, 6.7 Hz, 1H), 4.95 (app dq, J = 17.2, 1.8 Hz, 1H), 4.90 (ddt, J = 10.3, 2.1, 1.2 Hz, 1H), 3.69 (s, 3H), 3.20 (t, J = 7.5 Hz, 1H), 2.01 (app qt, J = 6.7, 1.1 Hz, 2H), 1.82 (app qt, J = 7.4 Hz, 2H), 1.42 (s, 9H), 1.41?1.33 (m, 2H), 1.33?1.25 (m, 2H).
  • 5
  • [ 33543-78-1 ]
  • [ 2695-47-8 ]
  • ethyl 1-(hex-5-en-1-yl)-1H-imidazole-2-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
94% With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 3h; General procedure: A mixture of <strong>[33543-78-1]ethyl 1H-imidazole-2-carboxylate</strong> (700mg, 5.0mmol), potassium carbonate (1.38g, 10.0mmol) and 4-bromobut-1-ene (800mg, 6.0mmol) in 5mL DMF was heated to 80C for 3h. TLC analysis indicated that the reaction had ceased. After cooling to room temperature, the solution was diluted with EtOAc (15mL) and washed with water (25mL*3), brine (25mL*3). The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was then purified by SiO2 chromatography (ethyl acetate: petroleum ether=1:1) to give compound 9d as colorless oil (0.93g, 96%).
  • 6
  • [ 95091-92-2 ]
  • [ 2695-47-8 ]
  • 1-(furan-2-yl)hept-6-en-1-one [ No CAS ]
  • 7
  • [ 109431-87-0 ]
  • [ 2695-47-8 ]
  • tert-butyl (R)-3-(hex-5-en-1-yloxy)pyrrolidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% With tetrabutylammomium bromide; sodium hydroxide; In n-heptane; water; at 80℃; for 2h; To a suspension of tert-butyl (R)-3-hydroxypyrrolidine-l-carboxylate (12.8 g, 68.4 mmol), tetrabutyl ammonium bromide (1.102 g, 3.42 mmol) and 6-bromo-l -hexene (13.71 mL, 103 mmol) in heptane (256 mL) was added sodium hydroxide (128 mL, 68.4 mmol, 50 wt% solution in water). The mixture was vigourously stirred at 80 C for 2 hours, then cooled to room temperature, diluted with water and extracted with heptane and twice with diethyl ether/heptane. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated in vacuo. Purification by column chromatography (600 g silica, 5 -> 14% ethyl acetate in heptane) afforded the desired product tert-butyl (R)-3- (hex-5-en-l-yloxy)pyrrolidine-l-carboxylate (14.93 g). Yield 81%. 'H NMR (400 MHz, Chloroform -if) d 5.87 - 5.74 (m, 1H), 5.05 - 4.91 (m, 2H), 4.04 - 3.95 (m, 1H), 3.48 - 3.27 (m, 6H), 2.07 (q, J = 7.2 Hz, 2H), 2.02 - 1.84 (m, 2H), 1.60 - 1.51 (m, 2H), 1.51 - 1.38 (m, 11H).
81% With tetrabutylammomium bromide; sodium hydroxide; In n-heptane; water; at 80℃; for 2h; [0144] To a suspension of tert-butyl (R)-3-hydroxypyrrolidine-1-carboxylate (12.8 g, 68.4 mmol), tetrabutylammonium bromide (1.102 g, 3.42 mmol) and 6-bromo-1-hexene (13.71 mL, 103 mmol) in heptane (256 mL) was added sodium hydroxide (128 mL, 68.4 mmol, 50 wt% solution in water). The mixture was vigourously stirred at 80 C for 2 hours, then cooled to room temperature, diluted with water and extracted with heptane and twice with diethyl ether/heptane. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated in vacuo. Purification by column chromatography (600 g silica, 5 -> 14% ethyl acetate in heptane) afforded the desired product tert-butyl (R)-3-(hex-5-en-1-yloxy)pyrrolidine-1-carboxylate (14.93 g). Yield 81%. 1H NMR (400 MHz, Chloroform-d) δ 5.87 - 5.74 (m, 1H), 5.05 - 4.91 (m, 2H), 4.04 - 3.95 (m, 1H), 3.48 - 3.27 (m, 6H), 2.07 (q, J = 7.2 Hz, 2H), 2.02 - 1.84 (m, 2H), 1.60 - 1.51 (m, 2H), 1.51 - 1.38 (m, 11H).
81% With tetrabutylammomium bromide; sodium hydroxide; In n-heptane; water; at 80℃; for 2h; To a suspension of tert-butyl (R)-3-hydroxypyrrolidine-l-carboxylate (12.8 g, 68.4 mmol), tetrabutyl ammonium bromide (1.102 g, 3.42 mmol) and 6-bromo-l -hexene (13.71 mL, 103 mmol) in heptane (256 mL) was added sodium hydroxide (128 mL, 68.4 mmol, 50 wt% solution in water). The mixture was vigourously stirred at 80 C for 2 hours, then cooled to room temperature, diluted with water and extracted with heptane and twice with diethyl ether/heptane. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated in vacuo. Purification by column chromatography (600 g silica, 5 -> 14% ethyl acetate in heptane) afforded the desired product tert-butyl (R)-3- (hex-5-en-l-yloxy)pyrrolidine-l-carboxylate (14.93 g). Yield 81%. 'H NMR (400 MHz, Chloroform -if) d 5.87 - 5.74 (m, 1H), 5.05 - 4.91 (m, 2H), 4.04 - 3.95 (m, 1H), 3.48 - 3.27 (m, 6H), 2.07 (q, J = 7.2 Hz, 2H), 2.02 - 1.84 (m, 2H), 1.60 - 1.51 (m, 2H), 1.51 - 1.38 (m, 11H).
 

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Technical Information

Categories

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