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Chemical Structure| 3747-74-8 Chemical Structure| 3747-74-8

Structure of 3747-74-8

Chemical Structure| 3747-74-8

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Product Details of [ 3747-74-8 ]

CAS No. :3747-74-8
Formula : C10H9Cl2N
M.W : 214.09
SMILES Code : ClCC1=NC2=CC=CC=C2C=C1.[H]Cl
MDL No. :MFCD00012734
InChI Key :WDETYCRYUBGKCE-UHFFFAOYSA-N
Pubchem ID :3083823

Safety of [ 3747-74-8 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302+H312-H314
Precautionary Statements:P260-P264-P270-P280-P301+P312+P330-P301+P330+P331-P303+P361+P353-P304+P340+P310-P305+P351+P338+P310-P362+P364-P405-P501
Class:8
UN#:3261
Packing Group:

Computational Chemistry of [ 3747-74-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 10
Fraction Csp3 0.1
Num. rotatable bonds 1
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 58.47
TPSA ?

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

12.89 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.0
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

3.42
Log Po/w (WLOGP)?

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

3.62
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.

2.72
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

3.43
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.64

Water Solubility

Log S (ESOL):?

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

-3.83
Solubility 0.032 mg/ml ; 0.00015 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.

-3.37
Solubility 0.0912 mg/ml ; 0.000426 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

-4.72
Solubility 0.00409 mg/ml ; 0.0000191 mol/l
Class?

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

Moderately 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

Yes
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.

-5.18 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)

1.53

Application In Synthesis of [ 3747-74-8 ]

* 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 [ 3747-74-8 ]

[ 3747-74-8 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 117011-70-8 ]
  • [ 3747-74-8 ]
  • [ 1365890-30-7 ]
YieldReaction ConditionsOperation in experiment
EXAMPLE 2 (Compound 2)Quinoline-2-(methyleneaminophenoxyisobutyric) Acid; A mixture of 1.95 g (0.01 mole) of 4-aminoiphenoxyisobutyric acid, 2.28 g (0.01 mole) of 2-chloromethylquinoline hydrochloride; 3 g of potassium carbonate,40 ml of water and 29 ml of isopropanol is refluxed and stirred for 24 hours and a dark brown solution with about 1 g of product is obtained. The product is worked up by adding sodium carbonate. Dithionite is added and the mixture is acidified with acetic acid and a brown powder is obtained. The structure is set forth as structure 2..C20H20N2O3; mw 336
  • 2
  • [ 5470-65-5 ]
  • [ 3747-74-8 ]
  • 2-[(3-bromo-4-nitrophenoxy)methyl]quinoline [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% With potassium carbonate; potassium iodide; In N,N-dimethyl-formamide; at 60℃; for 1.5h; To a mixture of <strong>[5470-65-5]3-bromo-4-nitrophenol</strong> (26, 4.91 g, 22.5 mmol), 2-(chloromethyl)quinoline hydrochloride (5.79 g, 27.0 mmol) and potassium iodide (374 mg, 2.25 mmol) in DMF (50 mL) was added K2CO3 (7.47 g, 54.1 mmol), and the mixture was stirred at 60 °C for 90 min. After cooling at room temperature, the mixture was diluted with EtOAc, and washed with water and brine. The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was washed with EtOAc?hexane to give 27 (6.89 g, 85percent) as a pale yellow solid. 1H NMR (CDCl3) delta 5.44 (s, 2H), 7.03?7.07 (m, 1H), 7.42 (d, 1H, J = 2.4 Hz), 7.55?7.62 (m, 2H), 7.74?7.80 (m,1H), 7.85 (d, 1H, J = 8.3 Hz), 7.96 (d, 1H, J = 9.3 Hz), 8.09 (d, 1H, J = 8.8 Hz), 8.23 (d, 1H, J = 8.3 Hz); MS (ESI) m/z 359, 361 [M+H]+.
  • 3
  • [ 50790-93-7 ]
  • [ 3747-74-8 ]
  • 2-butyl-1,3-bis(quinoline-2-ylmethyl)imidazolium chloride [ No CAS ]
  • 4
  • [ 50790-93-7 ]
  • [ 3747-74-8 ]
  • C17H19N3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
2-Butylimidazole (0.927 g, 7.46 mmol) dissolvedin acetonitrile (15 mL) was combined with potassium hydroxide (0.439 g, 9.23mmol) and stirred at 80C for 30 minutes. 2-(Chloromethyl)quinolinehydrochloride (1.27 g, 5.93 mmol), and potassium hydroxide (0.335 g, 5.97 mmol)were added to the reaction mixture which was heated at 80C overnight. The mixture was filtered toremove a white solid (presumed to be potassium chloride) and the volatiles wereremoved from the filtrate to yield a yellow oil. The oil was diluted withdichloromethane (30 mL) and washed with a basic aqueous solution (2 x 25 mL)and water (25 mL). The organic layer was dried with magnesium sulfate and thevolatiles were removed. The resulting yellow oil was resuspended inacetonitrile and 2-(chloromethyl)quinoline (1.14 g, 6.42 mmol) was added. Thereaction mixture was heated overnight at 80C. 11 precipitated from hot acetonitrile and was washed with coldacetonitrile (0.238 g, 9% yield).Mp: 196-198C. Found C, 69.5; H, 6.3; N, 12.1%.Calculated for C27H27N4Cl1: C,73.2; H, 6.1; N, 12.7%. Calculated for C26H25N4Cl1?H2O: C, 70.4; H, 6.3; N, 12.2%. HRMS (ESI+) calcd for C27H27N4+[M-Cl] of m/z = 407.2230, found m/z = 407.2199.1H NMR (500 MHz, DMSO- d6)delta = 8.51 (2H, d, Ar, J = 8.6 Hz), 8.04 (2H, d, Ar, J = 8.1 Hz), 7.97 (2H, s,Ar), 7.83 (2H, d, Ar, J = 8.3 Hz), 7.77 (2H, m, Ar), 7.64 (4H, m, Ar) 5.93 (4H, s, CH2), 3.12 (2H, q, CH2,J = 7.9 Hz), 1.24 (2H, m, CH2), 1.14 (2H, m, CH2), 0.51 (3H, t, CH3, J = 7.2 Hz). 13CNMR (125 MHz, DMSO- d6) delta= 154.4 (Ar), 148.7 (Ar), 146.8 (Ar), 137.5 (Ar), 130.1 (Ar), 128.4 (Ar), 128.0 (Ar), 127.2 (Ar), 127.0 (Ar), 122.9 (Ar),119.8 (Ar), 52.5 (CH2), 28.4 (CH2), 22.8 (CH2),21.5 (CH2), 13.1 (CH3). MS: m/z = 406.9 (theorfor M+ C27H27N4+ =407.2).Crystal data for 11-PF6?1.5(H2O):C54H60F12N8O3P2,M = 1159.04, Monoclinic, a = 15.1142(7) A, b = 48.741(2) A, c =7.3043(3) A, V = 5345.1412) A3, T = 100(2) K, space group P21/c,Z = 4, 53996 reflections measured,10736 [R(int) = 0.0592]. The final R1values were 0.0600 (I > 2sigma(I)).The final wR(F2) values were 0.1274 (I > 2sigma(I)). The final R1 values were 0.0913 (all data). The final wR(F2)values were 0.1433 (all data).
 

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Technical Information

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