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Chemical Structure| 4481-28-1 Chemical Structure| 4481-28-1
Chemical Structure| 4481-28-1

3-Carbamoylbenzoic acid

CAS No.: 4481-28-1

4.5 *For Research Use Only !

Cat. No.: A111256 Purity: 95%

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Product Details of [ 4481-28-1 ]

CAS No. :4481-28-1
Formula : C8H7NO3
M.W : 165.15
SMILES Code : O=C(O)C1=CC=CC(C(N)=O)=C1
MDL No. :MFCD04118098
Boiling Point : No data available
InChI Key :FVUKYCZRWSQGAS-UHFFFAOYSA-N
Pubchem ID :3014284

Safety of [ 4481-28-1 ]

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

Computational Chemistry of [ 4481-28-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 41.5
TPSA ?

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

80.39 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.77
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

1.01
Log Po/w (WLOGP)?

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

0.48
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.

0.79
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

0.37
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.68

Water Solubility

Log S (ESOL):?

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

-1.74
Solubility 3.02 mg/ml ; 0.0183 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.

-2.29
Solubility 0.852 mg/ml ; 0.00516 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

-1.35
Solubility 7.34 mg/ml ; 0.0445 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.

0.56

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)

1.08

Application In Synthesis of [ 4481-28-1 ]

* 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 [ 4481-28-1 ]

[ 4481-28-1 ] Synthesis Path-Downstream   1~30

  • 1
  • 3-(hydroxyimino-methyl)-benzoic acid [ No CAS ]
  • [ 4481-28-1 ]
  • 2
  • [ 106748-24-7 ]
  • [ 4481-28-1 ]
YieldReaction ConditionsOperation in experiment
With water; sodium hydroxide; In methanol; at 20℃; NaOH (107 mg, 2.68 mmol, 5.0 equiv.), in water (1.5 mL) wasadded in a solution of 23 (96 mg, 0.54 mmol,1.0 equiv.) in methanol(1.5 mL) and the resulting mixture was stirred at rt overnight. Themethanol was evaporated and the aqueous phase was acidifieduntil pH 2 using a solution of HCl 1N. The solid was filtered, and 24i was obtained as a white solid (72 mg, 0.44 mmol, 82%). 1H NMR(400 MHz, DMSO-d6) delta ppm 7.48 (s, 1H), 7.58 (t, 1H, J 7.7 Hz), 8.09(ddt, 2H, J 1.6 Hz, J 7.7 Hz, J 12.9 Hz), 8.15-8.18 (m, 1H), 8.45 (t,1H, J 1.6 Hz), 13.18 (s, 1H); 13C NMR (101 MHz, DMSO-d6) delta ppm128.9, 129.1, 131.4, 132.1, 132.3, 135.2, 167.4, 167.6.
  • 3
  • [ 75-44-5 ]
  • [ 55-21-0 ]
  • [ 4481-28-1 ]
  • 4
  • [ 618-47-3 ]
  • [ 4481-28-1 ]
  • 5
  • [ 7446-70-0 ]
  • [ 55-21-0 ]
  • sodium chloride [ No CAS ]
  • potassium chloride [ No CAS ]
  • silicon tetrachloride [ No CAS ]
  • [ 4481-28-1 ]
  • 6
  • [ 1877-71-0 ]
  • aqueous-methanolic ammonia [ No CAS ]
  • [ 4481-28-1 ]
  • 7
  • [ 106748-24-7 ]
  • methanolic NaOH-solution [ No CAS ]
  • [ 4481-28-1 ]
  • 8
  • [ 4481-28-1 ]
  • [ 21198-18-5 ]
  • [ 773056-98-7 ]
  • 11
  • [ 3441-03-0 ]
  • [ 4481-28-1 ]
  • 12
  • bis(diphenyl-phosphino)propane [ No CAS ]
  • [ 10388-19-9 ]
  • [ 4481-28-1 ]
YieldReaction ConditionsOperation in experiment
87% With triethylamine;palladium diacetate; In water; ethyl acetate; acetonitrile; B. 3-Carboxybenzamide A mixture of 3-iodobenzamide (4.28 g, 17.3 mmol), water (25.00 g, 1387.7 mmol), triethylamine (8.00 g, 79.1 mmol), palladium(II) acetate (0.28 g, 1.2 mmol), and bis(diphenylphosphino)propane (0.52 g, 1.3 mmol) in acetonitrile (50 mL) was pressurized to 40 psi with carbon monoxide and the pressure was released. After six such cycles, the bottle was pressurized again and the contents were stirred at 85 C. for 3 h. The reaction mixture was cooled to room temperature and depressurized. The solvent was evaporated and ethyl acetate (200 mL) was added. The solution was filtered and then extracted with water (2*200 mL). The combined aqueous layers were acidified with 12 M HCl to pH 0. The solid was filtered off and air-dried to give 3-carboxybenzamide (1.93 g, 87%) as a yellow solid
  • 13
  • [ 925159-45-1 ]
  • [ 4481-28-1 ]
  • [ 106748-24-7 ]
  • 14
  • [ 4481-28-1 ]
  • [ 1287769-49-6 ]
  • [ 1259931-90-2 ]
  • 15
  • [ 4481-28-1 ]
  • [ 1337543-32-4 ]
  • [ 1337544-62-3 ]
  • 16
  • [ 4481-28-1 ]
  • [ 1337543-32-4 ]
  • [ 1337544-65-6 ]
YieldReaction ConditionsOperation in experiment
Example 61a ethyl-4-amino-5-(2-(3-carbamoylbenzamido)-2-methylpropoxy)-2-methylquinoline-3-carboxylate Prepared as in Example 24a from 4-amino-5-(2-amino-2-methylpropoxy)-2-methylquinoline-3-carboxylate (Example 24b) and <strong>[4481-28-1]3-carbamoylbenzoic acid</strong> as a brown solid. MS 465 (MH+).
  • 17
  • [ 4481-28-1 ]
  • [ 1360052-15-8 ]
  • [ 1337544-62-3 ]
  • 18
  • [ 4481-28-1 ]
  • [ 1360052-15-8 ]
  • [ 1337544-65-6 ]
YieldReaction ConditionsOperation in experiment
Example 61a ethyl 4-amino-5-(2-(3-carbamoylbenzamido)-2-methylpropoxy)-2-methyl-quinoline-3-carboxylate Prepared as in Example 24a from 4-amino-5-(2-amino-2-methylpropoxy)-2-methylquino-line-3-carboxylate (Example 24b) and <strong>[4481-28-1]3-carbamoylbenzoic acid</strong> as a brown solid. MS 465 (MH+).
  • 19
  • [ 387350-79-0 ]
  • [ 4481-28-1 ]
  • C23H24F3N3O4S [ No CAS ]
  • 20
  • [ 4481-28-1 ]
  • 3-{4-methyl-5-[(3-{2-[4-(trifluoromethyl)phenyl]morpholin-4-yl}propyl)sulfanyl]-4H-1,2,4-triazol-3-yl}benzamide [ No CAS ]
  • 21
  • [ 4481-28-1 ]
  • 3-{5-[(3-chloropropyl)sulfanyl]-4-methyl-4H-1,2,4-triazol-3-yl}benzamide [ No CAS ]
  • 22
  • [ 4481-28-1 ]
  • [ 6610-29-3 ]
  • 3-(4-methyl-5-sulfanyl-4H-1,2,4-triazol-3-yl)benzamide [ No CAS ]
  • 23
  • [ 4481-28-1 ]
  • 3-[4-methyl-5-({3-[(1R,3S)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]benzamide [ No CAS ]
  • 24
  • [ 4481-28-1 ]
  • methyl 2-amino-2-(3',4',5'-trifluoro-[1,1'-biphenyl]-4-yl)acetate [ No CAS ]
  • methyl 2-(3-cyanobenzamido)-2-(3',4',5'-trifluoro-[1,1'-biphenyl]-4-yl)acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
89% [0125] To a nitrogen flushed 50 mL round bottom flask was added 3- carbamoylbenzoic acid (167 mg, 1 .01 mmol) in DCM (10 mL) and a catalytic amount of DMF (20 mu). Oxalyl chloride (130 mu, 1.51 mmol) was added dropwise and the mixture was stirred at room temperature for 1 h. DCM was concentrated in vacuo and a mixture of DIPEA (126 muIota_, 1.31 mmol) and compound methyl 2-amino-2-(3',4',5'-trifluoro-[1 ,1 '- biphenyl]-4-yl)acetate (13) (300 mg, 1 .01 mmol) in DCM (10 mL) were added. The mixture was stirred at room temperature for 30 min. The mixture was then diluted with water (15 mL) and extracted with DCM (3 x 10 mL). The combined organic layers were dried over Na2S04, filtered and concentrated in vacuo. The crude product was purified by column chromatography (eluent PE/EtOAC 100:0 to 0:100) to afford 383 mg (89%) of methyl 2-(3-cyanobenzamido)-2-(3',4',5'-trifluoro-[1 ,1 '-biphenyl]-4-yl)acetate (14h) as a clear oil. 1H NMR (CDCI3) delta 8.12 (s, 1 H), 8.06 (d, J = 7.9 Hz, 1 H), 7.80 (d, J = 7.8 Hz, 1 H), 7.58 (t, J = 7.7 Hz, 1 H), 7.54-7.48 (m, 4H), 7.44 (d, J = 6.7 Hz, 1 H), 7.19-7.10 (m, 2H), 5.79 (d, J = 6.7 Hz, 1 H), 3.81 (s, 3H); 19F NMR (CDCI3) delta -133.7 (d, J = 20.6 Hz), - 161.9 (dd, J = 20.6 Hz); 13C NMR (CDCI3) delta 171.1 , 164.7, 151 .6 (ddd, JCF = 250.0/10.1/4.2 Hz), 139.6 (dt, JCF = 252.4/15.4 Hz), 138.9-138.7 (m), 136.6-136.5 (m), 136.4, 135.3, 134.7, 131 .5, 131 .2, 129.8, 128.2, 127.7, 1 17.9, 1 13.2, 1 12.0-1 10.2 (m), 56.8, 53.4; m/z MS (TOF ES") C23H14F3N203 [M-H]" calcd 423.1 , found 423.1 ; LC-MS tR = 3.6.
  • 25
  • [ 4481-28-1 ]
  • [ 1448427-99-3 ]
  • N-{6-[4-(propan-2-yl)-4H-1,2,4-triazol-3-yl]pyridin-2-yl}benzene-1,3-dicarboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In ethyl acetate; at 100℃; for 16h;Inert atmosphere; General procedure: To a solution of 3-(ethylsulfonamido)benzoic acid (22, 60 mmol) and 6-[4-(propan-2-yl)-4H-1,2,4-triazol-3-yl]pyridin-2-amine (5, 50mmol) in EtOAC (1 mL)was added T3P (50% in EtOAc, 1 mL) and triethylamine (207 mmol).The vial was placed under a positive atmosphere of nitrogen, cappedand shaken at 100 C for 16 h. The reaction was concentratedunder reduced pressure and purified by HPLC (PhenomenexGemini C18 250 21.2 mm*8 mm; Acetonitrile-NH4OH (pH 10);gradient from 0% to 40% in 8 min, flow rate 35 mL/min).
  • 26
  • [ 4481-28-1 ]
  • [ 57667-50-2 ]
  • N-(1-propyl-1H-benzo[d]imidazol-2-yl)isophthalamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% 3-Carbamoylbenzoic acid (1 g, 0.006 mol) was dissolved in 10 mE of dry dimethylformamide (DMF) while stirring in a round bottom flask. HI3TU (2.73 g, 0.0072 moO/HOST hydrate (1.195 g, 0.0078 mol) solution was made with 15 mE DMF. HETU/HOST was added to the solution in the round bottom flask. 1 -propylbenzimidazol2-amine (1.157 mg, 0.0066 mol) in 15 mE DMF was injected and the solution was stirred for 20 minutes at room temperature. 4-methylmorpholine (1.98 mE, 0.018 mol) was added to the round bottom flask by syringe. The mixture was stirred until reaction completion (.- 12 hrs.). The reaction was quenched with 10 mE of deionized (DI) watet A precipitate was formed and isolated by vacuum filtration and washed with 10 mE of DI water to give the final product. Yield 1.56 g (80% yield)
  • 27
  • [ 4481-28-1 ]
  • [ 99281-88-6 ]
  • (E)-methyl 4-(3-carbamoylbenzamido)but-2-enoate [ No CAS ]
  • 28
  • [ 136-95-8 ]
  • [ 4481-28-1 ]
  • C15H11N3O2S [ No CAS ]
  • 29
  • nickel(II) sulfate hexahydrate [ No CAS ]
  • [ 4481-28-1 ]
  • tris(4-(1H-1,2,4-triazol-1-yl)phenyl)amine [ No CAS ]
  • [ 7732-18-5 ]
  • [Ni(tris(4-(1,2,4-triazol-1-yl)phenyl)amine)(5-aminoisophthalate)(H2O)]·3H2O}n [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; In N,N-dimethyl-formamide;Sonication; General procedure: A mixture of ttpa (0.50 mmol), 1,4-H2ndc (0.50 mmol), NiSO4·6H2O(0.50 mmol), NaOH (1.00 mmol), H2O (45.0 mL) and 5.0 mL DMF wereadded a beaker with stirring. The mixed solution containing 0.01M allreagents (0.01M ttpa, 0.01M 1,4-ndc, 0.01M Ni2+) was positioned inthe ultrasonic bath, and was sonochemical synthesis for 60 min at apower of 100W and frequency 40 kHz. The green powders 1 were obtainedby centrifugation, then washed using distilled water, and placedin air for dry, and characterized by powder X-ray diffraction analysis.Anal. Calc. for C36H32N10NiO8: C, 54.64%; H, 4.08%; N, 17.70%. Found: C, 54.43%; H, 3.92%; N, 17.51%. These processes were alsodone at (30 min, 100 W, 40 kHz), (60 min, 50 W, 40 kHz), (60 min,100 W, 20 kHz), (60 min, 100 W, 100 kHz), to research the effects ofsonication time, power and flrequency on the size and morphology oflnanostructural CP 1.
  • 30
  • nickel(II) sulfate hexahydrate [ No CAS ]
  • [ 4481-28-1 ]
  • tris(4-(1H-1,2,4-triazol-1-yl)phenyl)amine [ No CAS ]
  • [ 7732-18-5 ]
  • [Ni(tris(4-(1,2,4-triazol-1-yl)phenyl)amine)(5-aminoisophthalate)(H2O)]·3H2O}n [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; In N,N-dimethyl-formamide; at 110℃; for 72h;Autoclave; High pressure; A mixture of ttpa (0.20 mmol), 1,4-H2aip (0.20 mmol), NiSO4·6H2O(0.30 mmol), NaOH (0.38 mmol), H2O (9.0 mL) and 1.0 mL DMF wereadded to a Teflon-lined stainless autoclavz and this was sealed andheated to 110 C for 3 days and then cooled to room temperature. Thedark green crystals 4·3H2O were obtained. Anal. Calc. forC32H31N11NiO8 (4·3H2O): C, 50.81%; H, 4.13%; N, 20.37%. Found: C, 50.72%; H, 4.05%; N, 20.30. IR data (cm-1): 3192m, 1542s, 1513s,1472m, 1433w, 1376m, 1327w, 1302w, 1273m, 1242w, 1180w,1149w, 1117w, 1052w, 978s, 880w, 831m, 782m, 726m, 674s, 648w.
 

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Technical Information

Categories

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