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Chemical Structure| 5622-34-4 Chemical Structure| 5622-34-4
Chemical Structure| 5622-34-4

2-(Quinolin-6-yl)acetic acid

CAS No.: 5622-34-4

4.5 *For Research Use Only !

Cat. No.: A100734 Purity: 97%

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Product Details of [ 5622-34-4 ]

CAS No. :5622-34-4
Formula : C11H9NO2
M.W : 187.19
SMILES Code : O=C(O)CC2=CC=C1N=CC=CC1=C2
MDL No. :MFCD07776794
InChI Key :CFVILHFXMRQYSG-UHFFFAOYSA-N
Pubchem ID :11788709

Safety of [ 5622-34-4 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H301
Precautionary Statements:P264-P270-P301+P310+P330-P405-P501
Class:6.1
UN#:2811
Packing Group:

Calculated chemistry of [ 5622-34-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 10
Fraction Csp3 0.09
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 53.29
TPSA ?

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

50.19 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.33
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

1.67
Log Po/w (WLOGP)?

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

1.86
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.

1.36
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

2.15
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.68

Water Solubility

Log S (ESOL):?

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

-2.45
Solubility 0.665 mg/ml ; 0.00355 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.

-2.34
Solubility 0.859 mg/ml ; 0.00459 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

-3.48
Solubility 0.062 mg/ml ; 0.000331 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

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

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.

-6.26 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.

0.56

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

0.0 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)

1.27

Application In Synthesis of [ 5622-34-4 ]

* 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.

  • Upstream synthesis route of [ 5622-34-4 ]
  • Downstream synthetic route of [ 5622-34-4 ]

[ 5622-34-4 ] Synthesis Path-Upstream   1~1

  • 1
  • [ 67-56-1 ]
  • [ 5622-34-4 ]
  • [ 5622-36-6 ]
YieldReaction ConditionsOperation in experiment
98%
Stage #1: Reflux
Stage #2: With sodium hydroxide In ethyl acetateCooling with ice
Example 1. Preparation of 6-((5)-l-(6-(l-methyl-lH-pyrazol-4-yl)-[l,2,4]triazolo[3,4- δ][l,3,4]thiadiazol-3-yl)ethyl)quinoline (compound 1); [0064] As shown in step i of Scheme 1, concentrated sulfuric acid (206 mL, 3.868 mol) was added dropwise to a solution of 2-(quinolin-6-yl)acetic acid (compound 1001, 658.2 g, 3.516 mol, Okeanos Tech Co., Cat. No. OK-J-05024) in 6.5 liters of methanol. During the addition, a slight exotherm was observed. After the addition was complete, the reaction was stirred at reflux for 4 hours. After cooling, the volatiles were removed under reduced pressure, the resulting residue was diluted with 4 liters of ethyl acetate, cooled in an ice bath, treated with 2N NaOH (2.1 liters, 1.2 equiv.) until a pH of 4 was achieved, and then treated with saturated sodium bicarbonate until a pH of 8 was achieved. The layers were separated and the aqueous layer extracted twice with ethyl acetate. The combined organics were washed with saturated sodium bicarbonate, washed with water, washed with brine, dried over anhydrous MgSO4, filtered, and evaporated under reduced pressure to afford methyl 2-(quinolin-6-yl)acetate as a clear brown oil (compound 1002, 696.8 g, 98 percent yield): ESMS (M+l), 202.14; 1H NMR (300.0 MHz, DMSO-d6) δ 8.90 (IH, dd, J = 1.7, 4.2 Hz), 8.14 - 8.10 (IH, m), 8.08 (IH, d, J = 8.7 Hz), 7.72 (IH, d, J = 1.4 Hz), 7.65 (IH, dd, J = 2.0, 8.7 Hz), 7.40 (IH, dd, J = 4.2, 8.3 Hz), 3.83 (2H, s), 3.73 (3H, s).
85% at 20℃; for 6 h; To a solution of 2-(quinolin-6-yl)acetic acid (2.0 g, 11 mmol) in methanol (40 mL) wasadded concentrated sulphuric acid (0.2 mL). The mixture was stirred at roomtemperature for 6 hours. The reaction mass was poured into water and the resulting solution was neutralised with saturated NaHCO3 solution and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over Na2504 and evaporated in vacuo to give methyl 2-(quinolin-6-yl)acetate (1.8 g, 85percent). LCMS: m/z202.25 [M+H].
76% With thionyl chloride In methanol at 0℃; for 2 h; Reflux 2-(quinolin-6-yl)acetic acid (12.0 g, 0.064 mol) was dissolved in dry MeOH (120 mL) and cooled to 0 °C. SOCl2 (7.0 mL, 0.096 mol) was added, and the reaction mixture was refluxed for 2 h. The reaction mixture was concentrated under reduced pressure and the resultant residue was dissolved in EtOAc, washed with water and brine, dried over anhydrous Na2SO/t, filtered, and concentrated under reduced pressure. The resultant residue was purified by columnchromatography (20 - 25percent EtOAc/petroleum ether) to afford the title compound (9.8 g, 76percent).TLC: 20percent MeOH/CH2Cl2, Rf= 0.6. lU NMR (300 MHz, DMSO-d6) δ ppm 8.86 (dd, J= 4.3, 1.6 Hz, 1H), 8.32 - 8.29 (m, 1H), 7.97 (d, J= 8.6 Hz, 1H), 7.84 (m, 1H), 7.66 (dd, J= 8.8, 2.0 Hz, 1H), 7.50 (dd, J= 8.2, 4.3 Hz, 1H), 3.90 (s, 2H), 3.63 (s, 3H).
73.6% for 3 h; Heating / reflux To a stirred solution of quinolin-6-yl-acetic acid (10 g, 53.0 mmol) in 100 ml of methanol was added 2.5 ml of concentrated H2SO4 The mixture was then heated to reflux for 3 hours. The reaction mixture was concentrated to give a brown residue, which was diluted with 100 ml of dichloromethane, washed with sat. aq.NaHCO3 and brine, then the organic layer was dried over anhydrous Na24 and concentrated to return title compound as a brown oil (7.9 g, 73.6percent).
72.6%
Stage #1: at 0 - 5℃; for 2 h; Heating / reflux
Stage #2: With sodium hydrogencarbonate In water; ethyl acetate
To a suspension of compound 2 (60 g, 0.32 mol) in MeOH (600 mL) cooled to 0~5°C, SOCI2 (30 mL, 0.35 mol) was added dropwise. After the mixture was heated to reflux for 2 h, the mixture was evaporated under reduced pressure, and the residue was taken up with EtOAc (600 mL). The mixture was washed with aq. NaHCO3 and brine, dried over Na2SO4 and concentrated to give crude product, which was purified via a silica column chromatography (EtOAc: Petroleum ether = 1 :5) to give pure compound 3 (50 g, 72.6percent) as a yellow oil. 1H NMR (400 MHz, CDCI3): δ 8.898-8.878 (dd, 1 H), 8.130-8.055 (m, 2H), <n="31"/>7.718 (s, 1 H), 7.670-7.634 (dd, 1 H), 7.407-7.365 (q, 1 H), 4.207-4.135(q, 2 H), 3.799(s, 2H), 1.279-1.232 (t, 3H).

References: [1] Patent: WO2010/59668, 2010, A1, . Location in patent: Page/Page column 20-21.
[2] Patent: WO2016/8011, 2016, A1, . Location in patent: Page/Page column 67.
[3] Patent: WO2013/19682, 2013, A1, . Location in patent: Page/Page column 117.
[4] Patent: WO2008/144767, 2008, A1, . Location in patent: Page/Page column 110; 115.
[5] Journal of Medicinal Chemistry, 2013, vol. 56, # 17, p. 6651 - 6665.
[6] Patent: WO2007/138472, 2007, A2, . Location in patent: Page/Page column 28-29.
 

Historical Records

Technical Information

Categories

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