13570-08-6|2-(1H-Benzo[d]imidazol-2-yl)acetic acid| Ambeed

CAS No. :	13570-08-6
Formula :	C₉H₈N₂O₂
M.W :	176.17
SMILES Code :	O=C(O)CC1=NC2=CC=CC=C2N1
MDL No. :	MFCD01102656
InChI Key :	GFTPLFVZKMIYAP-UHFFFAOYSA-N
Pubchem ID :	26117

Safety of [ 13570-08-6 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 13570-08-6 ] Show Less

Physicochemical Properties

Num. heavy atoms	13
Num. arom. heavy atoms	9
Fraction Csp3	0.11
Num. rotatable bonds	2
Num. H-bond acceptors	3.0
Num. H-bond donors	2.0
Molar Refractivity	47.64
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	65.98 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	0.6
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	1.08
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.19
Log P_o/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.	0.63
Log P_o/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	1.69
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.04

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.99
Solubility	1.79 mg/ml ; 0.0102 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.	-2.06
Solubility	1.54 mg/ml ; 0.00876 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	-2.69
Solubility	0.363 mg/ml ; 0.00206 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	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.	-6.61 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	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)	1.54

Application In Synthesis of [ 13570-08-6 ]

* 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 [ 13570-08-6 ]

[ 13570-08-6 ] Synthesis Path-Downstream 1~49

2
[ 13570-08-6 ]
[ 64-17-5 ]
[ 14741-71-0 ]

Yield	Reaction Conditions	Operation in experiment
	With sulfuric acid; for 7h;Reflux;	A solution of compound (4a-b) (4 g, 0.022 mol) in absoluteethanol (15 mL) was refluxed for 7 h in presence of conc. H2SO4(0.1 mL). After completion of the reaction, it was cooled to roomtemperature, then 2.14 ml (0.044 mol) of hydrazine hydrate wasadded and the reaction was further refluxed for another 8 h.Detecting single-spot in TLC using the solvent system chloroform:methanol (9:1), the reaction mixture was poured in ice. A precipitateformed (6a-b) which was filtered, washed with water andcrystallized from ethanol.

References: [1]Research on Chemical Intermediates,2012,vol. 38,p. 1403 - 1409.
[2]European Journal of Medicinal Chemistry,2017,vol. 126,p. 853 - 869.

3
[ 13570-08-6 ]
[ 67-63-0 ]
[ 1354647-66-7 ]

References: [1]Research on Chemical Intermediates,2012,vol. 38,p. 1403 - 1409.

4
[ 13570-08-6 ]
[ 71-36-3 ]
[ 1354647-67-8 ]

References: [1]Research on Chemical Intermediates,2012,vol. 38,p. 1403 - 1409.

5
[ 13570-08-6 ]
[ 615-15-6 ]

References: [1]Research on Chemical Intermediates,2012,vol. 38,p. 1403 - 1409.

6
[ 13570-08-6 ]
[ 1354647-68-9 ]

References: [1]Research on Chemical Intermediates,2012,vol. 38,p. 1403 - 1409.

7
[ 13570-08-6 ]
[ 284497-05-8 ]

References: [1]Research on Chemical Intermediates,2012,vol. 38,p. 1403 - 1409.

8
[ 13570-08-6 ]
[ 1032-97-9 ]

References: [1]Research on Chemical Intermediates,2012,vol. 38,p. 1403 - 1409.

9
[ 67-56-1 ]
[ 13570-08-6 ]
[ 49672-05-1 ]

Yield	Reaction Conditions	Operation in experiment
86%	With thionyl chloride; at 0 - 20℃; for 18h;	Thionyl dichloride (0.7 ml, 9.65 mmol) was added dropwise to an ice-cooled (0C) suspension of 2-(1H-1,3- benzodiazol-2-yl)acetic acid (179) (0.7 g, 3.97 mmol) in MeOH (30 ml). The reaction mixture was allowed to warm to room temperature and stirred for 18 h. The mixture was poured onto saturated NaHCQ (40 ml) and extracted with DCM (3 x 20 ml). The combined organic layers were washed with brine (30 ml), dried (NaS04), filtered and evaporated to give the title compound (0.65 g, 86%) as a cream solid. 1H-NMR(CDCI3, 500 MHz): d[ppm]= 10.10 (brs, 1H), 7.72 (brs, 1H), 7.46 (brs, 1H), 7.29-7.23 (m, 2H), 4.09 (s, 2H), 3.82 (s, 3H) HPLCMS (Method F): [m/z]: 191.2 [M+Hf

References: [1]Patent: WO2017/68089,2017,A2 .Location in patent: Page/Page column 243.
[2]Research on Chemical Intermediates,2012,vol. 38,p. 1403 - 1409.

10
[ 13570-08-6 ]
[ 1383735-39-4 ]
[ 1571819-66-3 ]

Yield	Reaction Conditions	Operation in experiment
23%	With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 20℃; for 1h;	Example 64 Synthesis of 2-[1H-benzimidazo-2-yl)-1-[1-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]ethanone To a mixture of <strong>[13570-08-6](1H-benzoimidazol-2yl)acetic acid</strong> (41 mg, 0.23 mmol) and 1-(4-fluorophenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-b]pyridine (50 mg, 0.23 mmol) in DMF (1 mL) was added Hunig's base (59 mg, 0.46 mmol) and 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uranium hexafluorophosphate methanaminium (HATU, 96 mg, 0.2 mmol). The mixture was stirred at room temperature for 1 hour and then was partitioned between water (4 mL) and ethyl acetate (6 mL). The organic layer was washed with brine and dried (Na2SO4), filtered, concentrated in vacuo, and purified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent) to give the desired product as a white solid (0.020 g, 23%). 1H NMR (400 MHz, CDCl3) delta 8.38 (s, 0.8H), 8.00 (s, 1H), 7.85 (m, 1H), 7.61 (s, 0.2H), 7.52-7.43 (m, 2H), 7.36-7-29 (m, 3H), 7.23-7.14 (m, 2H), 5.18 (s, 2H), 3.84 (m, 2H), 2.88 (m, 2H), 2.13 (m, 2H); MS: (ES) m/z calculated for C21H16ClF4N3O [M+H]+ 376.1, found 376.1.

References: [1]Patent: US2014/57937,2014,A1 .Location in patent: Paragraph 0285; 0286.

11
[ 13570-08-6 ]
[ 1602748-91-3 ]

References: [1]Patent: US2014/114067,2014,A1 .
[2]European Journal of Medicinal Chemistry,2017,vol. 125,p. 1172 - 1192.

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[ 13570-08-6 ]
[ 1602748-93-5 ]

References: [1]European Journal of Medicinal Chemistry,2017,vol. 125,p. 1172 - 1192.

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[ 13570-08-6 ]
[ 2051-53-8 ]
[ 1602748-90-2 ]

Yield	Reaction Conditions	Operation in experiment
81%	With triethylamine; HATU; In acetonitrile; at 20℃; for 16h;	Example 79 2-(1H-benzo[d]imidazole-2-yl)-N-(5-isopropyl-2-methylphenyl)acetamide 2-(1H-benzo[d]imidazole-2-yl)acetic acid (100 mg, 0.57 mmol), O-(7-azabenzotriazol-1-yl)-M,M,N',N'-tetramethyluronium hexafluorophosphate (HATU, 433 mg, 1.14 mmol) are dissolved into acetonitrile (7 mL). Triethylamine (TEA, 160 muL, 1.14 mmol) is added thereto and 5-isopropyl-2-methylaniline (127 mg, 0.85 mmol) is further added dropwise thereto. After the reaction mixture is allowed to react for 16 hours at room temperature, TLC is performed to determine the completion of the reaction. The reaction mixture is concentrated under reduced pressure and extracted with water and ethyl acetate. The organic layer is dried with dry sodium sulfate. Column chromatography (EA:n-Hex=1:2) is carried out to obtain 170 mg of the target compound (yield: 81%). 1H NMR (400 MHz, DMSO-d6) delta ppm 12.37 (s, 1H) 9.91 (s, 1H) 7.56 (d, J=7.28 Hz, 1H) 7.47 (d, J=7.16 Hz, 1H) 7.43 (s, 1H) 7.14 (m, 3H) 6.95 (d, J=7.64 Hz, 1H) 4.02 (s, 2H) 2.82 (q, J=7.01 Hz, 1H) 2.20 (s, 2H) 1.17 (s, 3H) 1.15 (s, 3H)
81%	With triethylamine; HATU; In acetonitrile; at 20℃;Inert atmosphere;	A mixture of <strong>[13570-08-6]2-(1H-benzo[d]imidazol-2-yl)acetic acid</strong> 46 (100 mg, 0.57 mmol), 5-isopropyl-2-methylaniline 47, HATU (433 mg, 1.14 mmol), and Et3N (160 muL, 1.14 mmol) in MeCN (7 mL) was stirred at room temperature for 4 h. And then, isopropyl-2-methylaniline (127 mg, 0.85 mmol) was added. After stirring at room temperature for 12 h, the mixture was extracted with EtOAc (3 ~ 30 mL) and washed with H2O (~ 30 mL). The organic layer was dried over anhydrous MgSO4, and concentrated in vacuo to yield the title product 48 (170 mg, 81%); 1H NMR (400 MHz, DMSO-d6) delta ppm 12.37 (br s, 1H) 9.91 (s, 1H) 7.56 (d, J = 7.2 Hz, 1H) 7.47 (d, J = 7.2 Hz, 1H) 7.43 (s, 1H) 7.14 (m, 3H) 6.95 (d, J = 7.6 Hz, 1H) 4.02 (s, 2H) 2.82 (m, 1H) 2.20 (s, 3H) 1.17 (s, 3H) 1.15 (s, 3H); LC/MS (ESI+, MeCN/H2O): m/z: calcd for C19H22N3O: 308.17 [M + H]+; found: 308.2.

References: [1]Patent: US2014/114067,2014,A1 .Location in patent: Paragraph 0307-0308.
[2]European Journal of Medicinal Chemistry,2017,vol. 125,p. 1172 - 1192.

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[ 13570-08-6 ]
[ 1602747-88-5 ]

References: [1]European Journal of Medicinal Chemistry,2017,vol. 125,p. 1172 - 1192.

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[ 13570-08-6 ]
[ 1602747-92-1 ]

References: [1]European Journal of Medicinal Chemistry,2017,vol. 125,p. 1172 - 1192.

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[ 13570-08-6 ]
[ 1602747-95-4 ]

References: [1]European Journal of Medicinal Chemistry,2017,vol. 125,p. 1172 - 1192.

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[ 13570-08-6 ]
2-((1H-benzo[d]imidazol-2-yl)methyl)-5-(4-methoxyphenyl)-1,3,4-oxadiazole [ No CAS ]