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Chemical Structure| 3355-28-0 Chemical Structure| 3355-28-0

Structure of 3355-28-0

Chemical Structure| 3355-28-0

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Product Details of [ 3355-28-0 ]

CAS No. :3355-28-0
Formula : C4H5Br
M.W : 132.99
SMILES Code : CC#CCBr
MDL No. :MFCD00190233
InChI Key :LNNXOEHOXSYWLD-UHFFFAOYSA-N
Pubchem ID :2756862

Safety of [ 3355-28-0 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H225-H315-H319-H335
Precautionary Statements:P210-P240-P241-P242-P243-P261-P264-P271-P280-P303+P361+P353-P304+P340-P305+P351+P338-P312-P363-P370+P378-P403+P233-P501
Class:3
UN#:1993
Packing Group:

Computational Chemistry of [ 3355-28-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 5
Num. arom. heavy atoms 0
Fraction Csp3 0.5
Num. rotatable bonds 0
Num. H-bond acceptors 0.0
Num. H-bond donors 0.0
Molar Refractivity 27.37
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.

1.97
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

1.61
Log Po/w (WLOGP)?

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

1.48
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.

2.27
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

1.27
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.72

Water Solubility

Log S (ESOL):?

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

-1.68
Solubility 2.79 mg/ml ; 0.0209 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.

-1.22
Solubility 7.98 mg/ml ; 0.06 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

-1.57
Solubility 3.55 mg/ml ; 0.0267 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.

-5.97 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

3.0
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)

3.91

Application In Synthesis of [ 3355-28-0 ]

* 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 [ 3355-28-0 ]

[ 3355-28-0 ] Synthesis Path-Downstream   1~13

  • 1
  • [ 13529-27-6 ]
  • [ 3355-28-0 ]
  • 2-(1-Ethoxy-2-methyl-buta-2,3-dienyl)-furan [ No CAS ]
  • 2
  • [ 2142-06-5 ]
  • [ 3355-28-0 ]
  • 1-benzyl-5-but-2-ynyl-5-hydroxy-pyrrolidin-2-one [ No CAS ]
  • 3
  • [ 3355-28-0 ]
  • [ 18938-60-8 ]
  • [ 827036-34-0 ]
YieldReaction ConditionsOperation in experiment
95% With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 15h; To an anhydrous N,N-dimethylformamide solution (2.0 mL) of N-t-butoxycarbonyl-L-tyrosine-t-butyl ester (338 mg, 1.0 mM), potassium carbonate (173 mg, 1.25 mM) and 1-bromo-2-butyne (147 mg, 1.1 mM) were added, followed by stirring at room temperature for 15 hours. Ethyl acetate (30 mL) was added to the reaction solution, followed by washing three times with water (20 mL) and with brine (20 mL) sequentially. The ethyl acetate layer was dehydrated and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. Subsequently, the resulting oily substance was purified by silica gel column chromatography. From n-hexane/ethyl acetate (5:1) eluted fraction, Compound 48 (370 mg, 95%) was obtained as a colorless oily substance. Physicochemical property of Compound 48 Molecular weight: 389 FAB-MS (positive mode, matrix m-NBA) 390 (M+H+) 1H-NMR Chemical shift value delta (in deuterated chloroform): 1.41 (9H, s), 1.42 (9H, s), 1.86 (3H, t, J=2.5Hz), 3.00 (2H, d, J=6.0Hz), 4.41 (1H, dd, J=7.5, 6.0Hz), 4.62 (2H, q, J=2.5Hz), 4.97 (1H, d, J=7.5Hz), 6.88 (2H, d, J=8.5Hz), 7.08 (2H, d, J=8.5Hz)
  • 4
  • [ 705280-65-5 ]
  • [ 3355-28-0 ]
  • [ 705280-60-0 ]
YieldReaction ConditionsOperation in experiment
92% With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 20℃; EXAMPLE V dimethyl 2-bromo-3-(2-butyn-1-yl)-1H-imidazole-4,5-dicarboxylate 4.53 ml of 1-bromo-2-butyne are added to 13.20 g <strong>[705280-65-5]dimethyl 2-bromo-1H-imidazole-4,5-dicarboxylate</strong> and 8.57 g potassium carbonate in 70 ml N,N-dimethylforrnamide and the reaction mixture is stirred overnight at ambient temperature. For working up it is combined with water and extracted with ethyl acetate. The combined organic phases are dried over magnesium sulphate and evaporated down. Yield: 14.58 g (92% of theory) Mass spectrum (ESI+): m/z=315, 317 [M+H]+
75% With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; for 2.0h;Heating / reflux; 136a) dimethyl 2-bromo-1-(but-2-ynyl)-1H-imidazol-4,5-dicarboxylate A solution of 15.0 g (57.0 mmol) of dimethyl 2-bromo-imidazole-4,5-dicarboxylate, 5.15 ml (57.0 mmol) of 1-bromo-2-butyne and 50 ml of N,N-diisopropylethylamine in 280 ml of tetrahydrofuran was refluxed for one hour. The mixture was concentrated by evaporation, the residue combined with approx. 100 ml of water and extracted three times with 70 ml of ethyl acetate. The extracts were washed with 50 ml of water, dried and evaporated down. The crude product thus obtained was purified by column chromatography (silica gel; eluant:dichloromethane with 0-2% ethanol). Yield: 75% of theory. C11H11BrN2O4 (315.13) Rf value: 0.82 (silica gel; dichloromethane/ethanol 9:1) Mass spectrum: (M+H)+=315/317
75% With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; for 1.0h;Heating / reflux; EXAMPLE I Dimethyl 2-bromo-1-(2-butyn-1-yl)-1H-imidazole-4,5-dicarboxylate A solution of 15.0 g dimethyl 2-bromo-imidazole-4,5-dicarboxylate, 5.15 ml 1-bromo-2-butyne and 50 ml N,N-diisopropylethylamine in 280 ml of tetrahydrofuran is refluxed for one hour. The mixture is concentrated by evaporation, the residue is combined with approx. 100 ml of water and extracted three times with 70 ml of ethyl acetate. The extracts are washed with 50 ml of water, dried and evaporated down. The crude product thus obtained is purified by column chromatography through silica gel with methylene chloride/ethanol (1:0→49:1) as eluant. Yield: 13.50 g (75% of theory) Rf value: 0.82 (silica gel, methylene chloride/ethanol=9:1) Mass spectrum (ESI+): m/z=315/317 (Br) [M+H]+
75% With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; for 1.0h;Heating / reflux; EXAMPLE IX Dimethyl 2-bromo-1-(2-butyn-1-yl)-1H-imidazole-4,5-dicarboxylate A solution of 15.0 g of dimethyl 2-bromo-imidazole-4,5-dicarboxylate, 5.15 ml of 1-bromo-2-butyne and 50 ml of N,N-diisopropylethylamine in 280 ml of tetrahydrofuran is refluxed for one hour. The mixture is concentrated by evaporation, the residue is combined with approx. 100 ml of water and extracted three times with 70 ml of ethyl acetate. The extracts are washed with 50 ml of water, dried and evaporated down. The crude product thus obtained is purified by column chromatography through silica gel using methylene chloride/ethanol (100:0 to 98:2) as eluant. Yield: 13.50 g (75% of theory) Rf value: 0.82 (silica gel, methylene chloride/ethanol=9:1) Mass spectrum (ESI+): m/z=315, 317 [M+H]+
74% With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 12.0h; b) dimethyl 2-bromo-1-(but-2-ynyl)-1H-imidazole-4,5-dicarboxylate 3.06 g 1-bromo-2-butyne are added dropwise to a mixture of 6.00 g of <strong>[705280-65-5]dimethyl 2-bromo-1H-imidazole-4,5-dicarboxylate</strong> and 3.80 g of potassium carbonate in 40 ml of dimethylformamide. The mixture is stirred for 12 h at ambient temperature and then added to an aqueous saturated solution of sodium thiosulphate. The organic phase is separated off and the aqueous phase is extracted three times with ethyl acetate. The combined organic phases are dried over sodium sulphate, the solvent is removed and the residue is chromatographed over silica gel (cyclohexane/ethyl acetate 4:1>1:1). Yield: 5.28 g (74% of theory) Mass spectrum (ESI+): m/z=315/317 (Br) [M+H]+

  • 5
  • [ 3513-81-3 ]
  • [ 3355-28-0 ]
  • [ 1015098-87-9 ]
  • 6
  • [ 6812-16-4 ]
  • [ 3355-28-0 ]
  • C12H11NO2 [ No CAS ]
  • 7
  • [ 13589-72-5 ]
  • [ 3355-28-0 ]
  • C11H8ClNO [ No CAS ]
  • 8
  • [ 83345-46-4 ]
  • [ 3355-28-0 ]
  • t-butyl [(S)-2-(4-but-2-ynyloxy-phenyl)-1-hydroxymethyl-ethyl]-carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
719 mg With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 3h;Inert atmosphere; t-Butyl [(S)-2-(4-but-2-ynyloxy-phenyl)-1-hydroxymethyl-ethyl]-carbamate 4-((S)-2-Amino-3-hydroxy-propyl)-phenol hydrochloride (500 mg, 2.45 mmol) was dissolved in methanol (8.2 mL), and di-tert-butyl dicarbonate (1.24 mL, 5.39 mmol) and triethylamine (343 muL, 2.45 mmol) were added at room temperature. The reaction mixture was stirred for 3 hours, then poured into an aqueous solution of sodium bicarbonate, and extracted with ethyl acetate. The organic extract was washed with a saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was dissolved in DMF (7.5 mL). To the solution were added 1-bromo-but-2-yne (0.217 mL, 2.48 mmol) and potassium carbonate (389 mg, 2.82 mmol) at room temperature. The reaction mixture was stirred at room temperature for 3 hours. A saturated brine was added, and the mixture was extracted with ethyl acetate. The organic extract was dried over magnesium sulfate, and concentrated under reduced pressure to obtain the title compound (719 mg, 94% yield). ESI (LC/MS positive mode) m/z 320 (M+H); Rt 2.10 min.
  • 9
  • [ 455-37-8 ]
  • [ 3355-28-0 ]
  • N,N-di(but-2-yn-1-yl)-3-fluorobenzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% N,N-di(but-2-yn- 1 -yI)-<strong>[455-37-8]3-fluorobenzamide</strong> To an ice cold solution of 1 -bromobut-2-yne (7.15 g, 53.8 mmol) in anhydrous DMF (45 mL) was added NaH (60%, 2.44 g, 61 .1 mmol). After stirring at 0 CC for 15 mm, a solution of 3- fluorobenzamide (3.4 g, 24.4 mmol) in anhydrous DMF (5 mL) was added dropwise over 1 hr. The resulting mixture was warmed up to RT and stirred for 1 hr before being quenched with water (100 mL) and extracted with ether (2x200 mL). The the combined ether solutions were were washed with brine, dried over Na2SO4 and concentrated under reduced pressure to give the crude product which was purified by column chromatography (silica gel, 0-15% EtOAc/petroleum ether) to afford N,N-di(but-2-yn-1 -yl)-<strong>[455-37-8]3-fluorobenzamide</strong> (4.78 g, 80% yield) as a yellow oil.
  • 10
  • [ 65938-77-4 ]
  • [ 3355-28-0 ]
  • N,N-bis(2-butynyl)-(5-methyl-2-pyridyl)sulfonamide [ No CAS ]
  • 11
  • [ 40187-51-7 ]
  • [ 3355-28-0 ]
  • C13H13NO3 [ No CAS ]
  • 12
  • [ 3355-28-0 ]
  • [ 257937-08-9 ]
  • C14H17BrN2O2 [ No CAS ]
  • 13
  • C16H13BrN6O2 [ No CAS ]
  • [ 3355-28-0 ]
  • [ 853029-57-9 ]
YieldReaction ConditionsOperation in experiment
86.3% With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 50℃; for 3h; A 1 L four-neck reaction flask was charged with compound V (40.0 g, 0.10 mol) and DMF (150 ml). After stirring for 30min, N, N-diisopropylethylamine (25.5g, 0.197mol) was slowly added to the system. After the addition was completed, the system was heated to 50 C in a hot water bath.A solution of 1-bromo-2-butyne (14.5 g, 0.11 mol) in DMF (40 mL) was then slowly added dropwise to the system. After the dropwise addition was completed, the system was stirred at 50 C. for 3 hours to reach the TLC plate until the starting compound V disappeared. The system was cooled down to 10 C, a large amount of solid was precipitated, H2O (300 mL) was added to the system, and then the system was cooled down to 5 C and stirred for 1 h. It was filtered with a Buchner funnel, and the obtained solid was washed with EtOH (300 mL) cooled in advance, and then the solid was blow-dried at 50 C to obtain a pale yellow solid (Compound Formula VI) (39.1 g, 86.3%).
 

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