Structure of 4481-28-1
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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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 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
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 |
80.39 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.77 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.01 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.48 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.79 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.37 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.68 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.74 |
Solubility | 3.02 mg/ml ; 0.0183 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.29 |
Solubility | 0.852 mg/ml ; 0.00516 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.35 |
Solubility | 7.34 mg/ml ; 0.0445 mol/l |
Class? Solubility class: Log S scale |
Soluble |
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) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.59 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.56 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.08 |
* 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.
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation 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 |
Yield | Reaction Conditions | Operation 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+). |
Yield | Reaction Conditions | Operation 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+). |
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation 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). |
Yield | Reaction Conditions | Operation 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) |
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
28% | General procedure: A solution of 24 (1.0 equiv.), HOBt (1.1 equiv.) and EDC (1.5 equiv.) in DMF (1.3 mmol/mL) was stirred at rt for 15 minutes. The appropriate amine (2.0 equiv.) was added and the resulting solution was stirred at rt for 5 hours. Reaction media was diluted with water and aqueous phase was extracted 3 times with EtOAc. Combined organic layers were washed successively with a solution of HCl 1N, a saturated solution of NaHCO3 and brine, dried over Na2SO4 and concentrated. The resulting solid was then purified by column chromatography on silica gel using the appropriate heptanes:EtOAc mixture. |
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