40187-51-7|5-Acetyl-2-hydroxybenzamide| Ambeed

CAS No. :	40187-51-7
Formula :	C₉H₉NO₃
M.W :	179.17
SMILES Code :	CC(=O)C1=CC(C(N)=O)=C(O)C=C1
MDL No. :	MFCD00049222
InChI Key :	LWAQTCWTCCNHJR-UHFFFAOYSA-N
Pubchem ID :	198212

Safety of [ 40187-51-7 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H312-H315-H319-H332-H335
Precautionary Statements:	P261-P280-P305+P351+P338

Computational Chemistry of [ 40187-51-7 ] Show Less

Physicochemical Properties

Num. heavy atoms	13
Num. arom. heavy atoms	6
Fraction Csp3	0.11
Num. rotatable bonds	2
Num. H-bond acceptors	3.0
Num. H-bond donors	2.0
Molar Refractivity	46.75
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	80.39 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.16
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	1.13
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	0.69
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.	0.3
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	0.85
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	0.83

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.87
Solubility	2.4 mg/ml ; 0.0134 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.	-2.41
Solubility	0.694 mg/ml ; 0.00387 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	-1.75
Solubility	3.21 mg/ml ; 0.0179 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	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.	-6.59 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)	1.26

Application In Synthesis of [ 40187-51-7 ]

* 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 [ 40187-51-7 ]

[ 40187-51-7 ] Synthesis Path-Downstream 1~55

1
[ 5663-71-8 ]
[ 40187-51-7 ]

References: [1]Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences,1952,vol. 234,p. 1058.

2
[ 75-36-5 ]
[ 65-45-2 ]
[ 40187-51-7 ]

Yield	Reaction Conditions	Operation in experiment
92.2%	With aluminum (III) chloride; sodium chloride; at 140℃; for 0.666667h;	1), NaCl-AlCl3 low melting point mixed molten salt system preparation:A 100 ml three-necked flask,Mechanical agitation,Condensate tube (linked to tail gas HCl absorption device),0 ~ 200 thermometer and constant pressure dropping funnel consisting of the device placed in a constant temperature oil bath;Quickly weighed 0.0648 mol (about 8.64 g) of anhydrous aluminum chloride,0.0648 mol (about 3.79 g) of sodium chloride was added to the flask,Open the mechanical stirring, heating to 140 ,The solid is melted and the temperature is stable.Note: After about 25 minutes, anhydrous aluminum chloride, sodium chloride are in a molten state.2), weigh 0.036 mol (about 5.00 g) of salicylamide under stirring to add the flask(Flask temperature 140 )And melted,The temperature inside the flask is stable.3), weighed 0.0432 mol (about 3.39 g) of acetyl chloride,With a constant pressure dropping funnel through the condenser tube into the system,About 10min drops finished.The temperature of the drop was maintained at 140 C for 0.5 h,The reaction is complete.which is,The reaction was carried out in a NaCl-AlCl3 low melting point mixed molten salt system as a solvent.4), immediately after the completion of the reaction within the system slowly (that is, even within 5 minutes evenly added)60ml acid (composed of 1ml concentrated hydrochloric acid and 59ml ice water mixture)Producing a pale yellow solid,After the addition of the acid solution, the stirring was continued for 30 min at room temperature.At this point no longer produce light yellow solid;Get the suspension.5), filter the suspension,To give a pale yellow solid,And washed three times with hot water at 80 C (5 ml each)Drying (80 C, drying for 5 h) yields the crude product.6), and the resulting crude product was added with 20 ml of ethanol,Heated to reflux temperature,The crude product is completely dissolved,After the re-crystallization in the ice bath,Precipitation of the crystal filter drying (80 , drying 5h),To give 5-acetylsalicylamide as a white solid(Purity ? 98.1%), the yield was 92.2%.
88.5%		Step 3, 15g of AlCl3 and 7g of anhydrous, and 0.5g of self-made modified nano-scale solid acid catalyst was added to the vessel, stirred and heated to 180 C, then the intermediate salicylamide obtained above was added, and magnetic stirring was continued for 3 h;Step 4, then add 15g of acetyl chloride at a rate of 60 drops per minute, magnetically stirred, oil bath 180 C 4h;Step 5, adding 100 ml of 5% (V) hydrochloric acid solution to the reaction system, magnetic stirring at 60 C for 2 h, filtering, while recovering the self-made modified nano-scale solid acid catalyst, the filtrate is washed 5-8 times with deionized water to Neutral, constant temperature drying oven was dried at 110 C for 2 h, and the crude product was recrystallized from ethanol to give white solid 5-acetyl salicylamide.

References: [1]Heterocyclic Communications,2013,vol. 19,p. 23 - 28.
[2]Patent: CN104557604,2017,B .Location in patent: Paragraph 0039; 0040; 0041; 0042; 0043-0057; 0068-0075.
[3]Patent: CN110105236,2019,A .Location in patent: Paragraph 0009-0034; 0036.
[4]Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences,1952,vol. 234,p. 1058.

3
[ 40187-51-7 ]
[ 100-44-7 ]
[ 75637-30-8 ]

References: [1]Journal of Medicinal Chemistry,1982,vol. 25,p. 1363 - 1370.

4
[ 40187-51-7 ]
[ 77-76-9 ]
[ 142167-24-6 ]

References: [1]Chemical and Pharmaceutical Bulletin,1996,vol. 44,p. 734 - 745.

5
[ 40187-51-7 ]
[ 2550-36-9 ]
[ 189393-76-8 ]

References: [1]Tetrahedron Asymmetry,1999,vol. 10,p. 4393 - 4403.

6
[ 40187-51-7 ]
[ 100-39-0 ]
[ 75637-30-8 ]

Yield	Reaction Conditions	Operation in experiment
98%	With potassium carbonate; In acetonitrile;Reflux;	5-Acetyl-2-hydroxybenzamide (8.2g, 45.76 mmol), K2C03 (9.488g, 68.65 mmol, 1 .5 eq) and BnBr (8.609g, 5.987 mL, 50.34 mmol, 1 .1 eq) were heated under reflux in eCN (100 mL) overnight. The mixture remained a white suspension throughout. After removal of MeCN under reduced pressure, the crude product was dispersed in water (100 mL), and extraction with EtOAc (50 mL) was attempted. The white precipitate was found to be insoluble in either layer, and so was collected by filtration (vacuum) to give 9.41 g of white solid. The aqueous layer was separated in the filtrate and washed with EtOAc (50 mL). Concentration of the combined organic layers gave a white solid with an odour of BnBr. This was sonicated in PE, before filtering, and washing with a small amount of DCIWPE (1 :1 ). Total recovered yield of product: 12.077 g (98%).
98%	With potassium carbonate; In acetonitrile;Reflux;	5-Acetyl-2-hydroxybenzamide (4.1 ) (8.2g, 45.76 mmol), K2C03 (9.488g, 68.65 mmol, 1 .5 eq) and BnBr (8.609g, 5.987 mL, 50.34 mmol, 1 .1 eq) were heated under reflux in MeCN (100 mL) overnight. The mixture remained a white suspension throughout. After removal of MeCN under reduced pressure, the crude product was dispersed in water (100 mL), and extraction with EtOAc (50 mL) was attempted. The white precipitate was found to be insoluble in either layer, and so was collected by filtration (vacuum) to give 9.41 g of white solid. The aqueous layer was separated in the filtrate and washed with a further 50 mL of EtOAc. Concentration of the combined organic layers gave a white solid with an odour of BnBr. This was sonicated in PE, before filtering, and washing with a small amount of DCM/PE 1 :1 . The total recovered yield of product (4.2) is 12.077g (98%)

References: [1]Patent: WO2012/4549,2012,A1 .Location in patent: Page/Page column 58.
[2]Patent: WO2012/104659,2012,A1 .Location in patent: Page/Page column 32.
[3]Bioorganic and Medicinal Chemistry Letters,2001,vol. 11,p. 3123 - 3127.

7
[ 40187-51-7 ]
[ 73866-23-6 ]

References: [1]European Journal of Medicinal Chemistry,2004,vol. 39,p. 867 - 872.
[2]Canadian Journal of Chemistry,2011,vol. 89,p. 364 - 384.

8
[ 358-23-6 ]
[ 40187-51-7 ]
trifluoro-methanesulfonic acid 4-acetyl-2-carbamoyl-phenyl ester [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 2076 - 2080.

9
[ 40187-51-7 ]
[ 343339-00-4 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 2076 - 2080.

10
[ 40187-51-7 ]
[ 343339-01-5 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 2076 - 2080.

11
[ 40187-51-7 ]
2-furan-2-yl-5-[2-(5-methanesulfonyl-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazol-3-yl]-benzamide [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 2076 - 2080.

12
[ 40187-51-7 ]
2-furan-2-yl-5-[1-(5-methanesulfonyl-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazol-3-yl]-benzamide [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 2076 - 2080.

13
[ 40187-51-7 ]
2-hydroxy-5-(1,3-thiazol-5-yl)-benzamide [ No CAS ]