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Chemical Structure| 6940-78-9 Chemical Structure| 6940-78-9

Structure of 1-Bromo-4-chlorobutane
CAS No.: 6940-78-9

Chemical Structure| 6940-78-9

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Product Details of [ 6940-78-9 ]

CAS No. :6940-78-9
Formula : C4H8BrCl
M.W : 171.46
SMILES Code : ClCCCCBr
MDL No. :MFCD00001010
InChI Key :NIDSRGCVYOEDFW-UHFFFAOYSA-N
Pubchem ID :81364

Safety of [ 6940-78-9 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H225
Precautionary Statements:P210-P403+P235
Class:3
UN#:1993
Packing Group:

Computational Chemistry of [ 6940-78-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 6
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 3
Num. H-bond acceptors 0.0
Num. H-bond donors 0.0
Molar Refractivity 34.01
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.

2.11
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

2.29
Log Po/w (WLOGP)?

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

2.4
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.

2.78
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

2.26
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.37

Water Solubility

Log S (ESOL):?

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

-2.15
Solubility 1.22 mg/ml ; 0.00712 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.

-1.93
Solubility 2.03 mg/ml ; 0.0118 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

-2.96
Solubility 0.187 mg/ml ; 0.00109 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.

-5.72 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

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)

2.61

Application In Synthesis of [ 6940-78-9 ]

* 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 [ 6940-78-9 ]

[ 6940-78-9 ] Synthesis Path-Downstream   1~12

  • 1
  • [ 6940-78-9 ]
  • [ 119838-38-9 ]
  • [ 123053-50-9 ]
  • 2
  • [ 219599-99-2 ]
  • [ 6940-78-9 ]
  • 8-(2-<i>tert</i>-butyl-6-trifluoromethyl-pyrimidin-4-yl)-8-aza-5-azonia-spiro[4.5]decane [ No CAS ]
  • 3
  • [ 6940-78-9 ]
  • [ 52851-41-9 ]
  • 2-(4-chloro-butoxy)-3<i>H</i>-quinolin-4-one [ No CAS ]
  • 1-(4-chloro-butyl)-1<i>H</i>-quinoline-2,4-dione [ No CAS ]
  • 4
  • [ 6940-78-9 ]
  • [ 22246-18-0 ]
  • [ 120004-79-7 ]
  • [ 129722-34-5 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate;tetrabutylammomium bromide; In water; at 90℃; for 2 - 3h;Product distribution / selectivity; EXAMPLE 1. Preparation of the mixture of 7-(4-chlorobutoxy)-3,4-dihydro- 2(lH)quinolinone and 7-(4-bromobutoxy)-3,4-dihydro-2(lH)quinolinone; 7-Hydroxy-3,4-dihydro-2(lH)quinolinone (20 g), l-bromo-4-chlorobutane (85 ml), K2CO3 (17 g), tetrabutylamrnonium bromide (2.0 g) and water (200 ml) were charged. The mixture was heated to 90 0C and stirred for 3 hours at about 90 °C. The water phase was separated off. The organic phase was washed with 100 ml of water at about 90 0C. Hexane (400 ml) was added at about 20 °C. The mixture was stirred for about 20 hours at room temperature and then cooled to about 0 °C. The crystalline mixture of 7-(4-chlorobutoxy)-3,4-dihydro-2(lH)quinolinone and 7- (4-bromobutoxy)-3,4-dihydro-2(lH)quinolinone was filtered and washed with hexane (3*20 ml). The product was dried under reduced pressure at 40-50 °C. The yield was 30.5 g (95.6 percent). The product was a 85:15 mixture of Cl- and Br- compounds. The HPLC-purity was 98.2 percent, the amount of dimeric impurity was 1.1 percent, per weight.; EXAMPLE 2. Preparation of the mixture of 7-(4-chlorobutoxy)-3,4-dihydro-2(lH)quinolinone and 7-(4-bromobutoxy)-3,4-dihydro-2(lH)quinolinone7-Hydroxy-3,4-dihydro-2(lH)quinolinone (20 g), l-bromo-4-chlorobutane (42.4 ml), K2CO3 (17 g), tetrabutylammonium bromide (2.0 g) and water (200 ml) were charged. The mixture was heated to 90 °C and stirred for 2 hours at about 90 °C. The water phase was separated off. The organic phase was washed with 100 ml of water at about 9O0C. Hexane (300 ml) was added at 20-40 °C. The mixture was stirred for about 20 hours at room temperature. The crystalline mixture of 7-(4- chlorobutoxy)-3,4-dihydro-2(lH)quinolinone and 7-(4-bromobutoxy)-3,4-dihydro- 2(lH)quinolinone was filtered and washed with hexane (3*50 ml). The product was dried under reduced pressure at 40-50 °C. The yield was 30.5 g (95 percent) The product <n="9"/>was a 79.9:20.1 mixture of Cl- and Br-compounds. The HPLC-purity was 94.2 percent, the amount of dimeric impurity was 3.1 percent, per weight.
  • 5
  • [ 6940-78-9 ]
  • [ 252061-66-8 ]
  • [ 1007455-38-0 ]
YieldReaction ConditionsOperation in experiment
98% With potassium carbonate; potassium iodide; In acetonitrile; for 18h;Heating / reflux; B17: 5-(4-Chloro-butoxy)-2,3-dihydro-isoindol-1 -oneTo a suspension of 5-Hydroxy-2,3-dihydro-isoindol-1-one (2.03 g, 13.6 mmol) in acetonitrile (17 mL) was added 1-bromo-4-chloro-butane (5.65 g, 32.9 mmol), potassium carbonate (4.63 g, 33.5 mmol), and potassium iodide (0.70 g, 0.31 mmol). After heating at reflux for 18 h the mixture was concentrated and crystallized from acetonitrile/water to obtain 5-(4-Chloro-butoxy)-2,3-dihydro-isoindol-1-one (B17), <3.23 g, 98 %). MS: ES: M+1 : 240.0 (239.6)
  • 6
  • [ 6940-78-9 ]
  • [ 21252-69-7 ]
  • 1-(4-chlorobutyl)-3-octylimidazolium hexafluorophosphate [ No CAS ]
  • 7
  • [ 6940-78-9 ]
  • [ 6374-91-0 ]
  • [ 1344698-20-9 ]
YieldReaction ConditionsOperation in experiment
75% General procedure: 5,7-dibromoisatin 2 (1 g, 3.28 mmol) was taken up in anhydrous DMF (30 mL) and cooled on ice with stirring. Solid K2CO3 (544 mg, 3.94 mmol) was added in one portion, and the dark colored suspension was brought to room temperature and stirred for a further 1 h. 1-Bromo-3-chloropropane (620 mg, 3.94 mmol, 0.387 mL) was added slowly with constant stirring and the reaction mixture was stirred at 80 C for 4-8 h, until the 5,7-dibromoisatin starting material had been consumed (TLC). The reaction mixture was poured into HCl (0.5 M, 50 mL) and extracted with ethyl acetate (3 × 50 mL). The ethyl acetate layer was washed with brine and dried over MgSO4. The solvent was removed, and the crude product was purified by silica gel column chromatography (CH2Cl2 as eluent) to give pure 3 (0.93 g, 74%) as orange red crystals.
  • 8
  • [ 6940-78-9 ]
  • [ 2785-78-6 ]
  • [ 1333889-83-0 ]
  • 9
  • [ 6940-78-9 ]
  • [ 64-65-3 ]
  • [ 1417033-91-0 ]
YieldReaction ConditionsOperation in experiment
51% With potassium carbonate; In N,N-dimethyl-formamide; at 0 - 20℃; General procedure: To a suspension of corresponding cyclic imide 1a-1k (4mmol), potassium carbonate (4.4mmol) in DMF (5mL), 1-bromo-4-chlorobutane (1,2-dibromoethane (5 eq) for 2l, 1-bromo-3-chloropropane for 2m, 1-bromo-5-chloropentane for 2n) (4.4mmol) was added dropwise at 0C. The mixture was stirred at room temperature overnight and then partitioned between ethyl acetate (EA, 20mL) and water (30mL). The organic layer was washed successively with water (3×30mL), saturated brine, and dried over anhydrous Na2SO4. The solvent was evaporated under vacuum and the residue was purified by column chromatography using petroleum ether(PE): EA (8:1) as eluent to give 2a-2n.
  • 10
  • [ 6940-78-9 ]
  • [ 53449-14-2 ]
  • 7-chloro-3-(4-chlorobutyl)-6-nitroquinazolin-4(3H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
91% With sodium hydride; In N,N-dimethyl-formamide; at 20 - 80℃; for 6h; General procedure: To a 100 mL flask was added 6a (f2 g, 9.7 mmol), DMF (20 mL)and 1-bromo-3-chloropentane (3 g, 19 mmol). The solution wasstirred at rt and added NaH (0.47 g, 19.6 mmol) and then heated to80 C for 6 h. After cooled to rt, the solution was poured onto icewater,extracted with dichloromethane, washed with brine anddried over Na2SO4. The crude product was purified by silica gelcolumn to afford 3-(3-chloropropyl)-6,7-dimethoxyquinazolin-4(3H)-one (7a) as an oil (1.7 g, yield 62%).
90.4% With sodium hydride; In N,N-dimethyl-formamide; at 80℃; for 8h; Intermediate 5 (3 g, 13.30 mmol) was added to a 100 mL round bottom flask at room temperature.Add 30 ml of anhydrous DMF, add 1-bromo-4-chlorobutane (3.4 g, 19.83 mmol) and NaH (0.6 g. 25 m-mol)After the temperature was raised to 80 C for 8 hours, the reaction was completed by TLC. After cooling, the reaction solution was poured into ice water, and a large amount of a yellow solid was precipitated, filtered, and dried to give a yellow solid product (3.8 g, yield 90.4%).
  • 11
  • [ 6940-78-9 ]
  • [ 19932-85-5 ]
  • 6-bromo-3-(4-chlorobutyl)-1,3-benzoxazol-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
1.2 g With potassium carbonate; In acetonitrile; at 80℃; for 12h; To a solution of 1-bromo-4-chlorobutane (2.17 mL, 18.7 mmol), K2CO3 (3.87 g, 28.04 mmol) in ACN (1 mL) was added dropwise at a solution of <strong>[19932-85-5]6-bromo-3H-1,3-benzoxazol-2-one</strong> (1) in ACN (3 mL). The mixture was heated at 80 C for 12 h. The inorganics were removed by filtration and the solvent was evaporated. The residue was purified by column chromatography (cyclohexane/ethyl acetate), 9:1 (v:v)) to afford 6-bromo-3-(4-chlorobutyl)-1,3-benzoxazol-2-one as a white solid (1.2 g, 3.94 mmol). Mp 61.9-62.4 C. 1H NMR (300 MHz, CDCl3): δ 7.39 (d, J = 1.8 Hz, 1H), 7.34 (dd, J = 8.3, 1.8 Hz, 1H), 6.88 (d, J = 8.3 Hz, 1H), 3.87 (t, J = 6.8 Hz, 2H), 3.60 (t, J = 6.1 Hz, 2H), 2.27-1.74 (m, 4H). 13C NMR (75 MHz, CDCl3): δ 154.1, 143.1, 130.2, 126.9, 114.8, 113.8, 109.2, 77.5, 77.0, 76.6, 44.0, 41.6, 29.2, 25.0. LCMS m/z calc for [M + ACN + H]+: 345.6, 347.6, found: 345.1, 347.1.
1.2 g With potassium carbonate; In acetonitrile; at 80℃; for 12h; To a solution of 1-bromo-4-chlorobutane (2.17 mL, 18.7 mmol), K2C03 (3.87 g, 28.04mmol) in ACN (1 mL) was added dropwise at a solution of <strong>[19932-85-5]6-bromo-3H-1,3-benzoxazol-2-one</strong> 1 in ACN (3 mL). The mixture was heated at 80C for 12 h. The inorganics were removed by filtration and the solvent was evaporated. The residue was purified by column chromatography (cyclohexane/ethyl acetate), 9:1 (v:v)) to afford 6-bromo-3-(4- chlorobutyl)-1,3-benzoxazol-2-one as a white solid (1.2 g). Mp 62C. 1H NMR (300 MHz), (5(ppm, CDC13): 7.39 (d, J= 1.7 Hz, 1H), 7.34 (dd, J= 8.3, 1.8 Hz, 1H), 6.88 (d, J= 8.3 Hz, 1H), 3.87 (t, J 6.8 Hz, 2H), 3.60 (t, J 6.1 Hz, 2H), 2.27 - 1.74 (m, 4H). 13C NMR (75 MHz), (5 (ppm, CDC13): 154.1, 143.1, 130.2, 126.9, 114.8, 113.8, 109.2, 77.5, 77.0, 76.6, 44.0, 41.6, 29.2, 25.0. LCMS m/z calc for [M+ACN+H]: 345.6, 347.6, found:345.1, 347.1.
  • 12
  • [ 6940-78-9 ]
  • [ 55687-30-4 ]
  • C13H15ClN2O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Compound 3-a (500 mg,3.36 mmol) was dissolved in DMF (6 mL), NaH (60% in mineral oil,270 mg, 6.72 mmol) was added in portions under ice bath followedby stirring for 1 h at 30 C. Then, 1,4-dibromobutane (3.63 g,16.8 mmol) was added followed by stirring at 30 C overnight. Thereaction mixture was extracted with ethyl acetate, washed threetimes with brine, dried, subjected to column chromatography usingthe mixture of petroleum etheracetone (40:1) as eluent to give 3-bas a pale yellow oil (820 mg, yield 86%). Compound 3-b (200 mg,0.70 mmol), 1-(benzo[b]thiophen-4-yl)piperazine hydrochloride(195 mg, 0.77 mmol) and potassiumcarbonate (242 mg,1.75 mmol)were added to acetonitrile (3 mL) under a nitrogen atmosphere andthe mixture was stirred at reflux for 5 h. The reaction mixture wasconcentrated, washed three times with brine, dried, subjected tocolumn chromatography to give 3 as a white solid (178 mg, 60%).
 

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