Structure of 10241-97-1
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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. : | 10241-97-1 |
Formula : | C10H9NO2 |
M.W : | 175.18 |
SMILES Code : | O=C(C(N1)=CC2=C1C=CC(C)=C2)O |
MDL No. : | MFCD00047166 |
InChI Key : | DAITVOCMWPNFTL-UHFFFAOYSA-N |
Pubchem ID : | 259188 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.1 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 50.22 |
TPSA ? Topological Polar Surface Area: Calculated from |
53.09 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.39 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.67 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.17 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.38 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.34 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.99 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.05 |
Solubility | 0.155 mg/ml ; 0.000882 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.44 |
Solubility | 0.0641 mg/ml ; 0.000366 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.04 |
Solubility | 0.159 mg/ml ; 0.00091 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 |
Yes |
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) |
Yes |
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 |
-5.47 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) |
1.39 |
* 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 |
---|---|---|
EXAMPLE 89 1-[5-Methylindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine (III) Following the general procedure of EXAMPLE 16 and making non-critical variations but starting with <strong>[10241-97-1]5-methylindole-2-carboxylic acid</strong> (0.23 g), 1-[3-(1-methylethylamino)-2-pyridinyl]piperazine (0.29 g) and 1,1'-carbonyldiimidazole (0.21 g) the title compound is obtained, mp 199°-201°. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 73 5-Methyl-1H-indole-2-carboxylic acid ((1S)-dimethylcarbamoyl-2-phenyl-ethyl)-amide (S)-2-Amino-N,N-dimethyl-3-phenyl-propionamide hydrochloride (1.0 mmol) and <strong>[10241-97-1]5-methyl-1H-indole-2-carboxylic acid</strong> (1.0 mmol) were coupled according to Procedure A (0 - 25 °C reaction temperature). The crude product was triturated with 1:1 ether-hexanes and dried. Yield 302 mg, 87 percent; HPLC (60/40) 5.46 minutes (99 percent); mp 198.5 - 200 °C; PBMS 350 (MH+, 100 percent); Anal. Calcd for C21H23N3O2: C, 72.18; H, 6.63; N, 12.04. Found: C, 72,14; H, 6.90; N, 12.11. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium bicarbonate; sulfuric acid; In methanol; | Preparation of Methyl 5-methylindole-2-carboxylate <strong>[10241-97-1]5-Methylindole-2-carboxylic acid</strong> (0.9 g, 5.13 mmol) was dissolved in methanol (25 ml) and treated with sulphuric acid (0.5 ml). The mixture was refluxed for 4 h. The volume of solvent was reduced and the residue treated with sodium hydrogen carbonate solution and extracted with ethyl acetate. The organic fractions were dried and concentrated to give the desired ester. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
[Example 114] (+-)-cis-N1-[(5-Methylindol-2-yl)carbonyl]-N2-[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]-pyridin-2-yl)carbonyl]-1,2-cyclohexanediamine hydrochloride: The title compound was obtained from (+-)-cis-N-[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclohexanediamine hydrochloride and <strong>[10241-97-1]5-methylindole-2-carboxylic acid</strong> in a similar manner to Example 6. 1H-NMR (DMSO-d6) delta: 1.35-1.50(2H,m), 1.50-1.80(4H,m), 1.85-2.07(2H,m), 2.36(3H,s),2.88(3H,s), 3.12(2H,br.s), 3.53(2H,br.s), 4.15-4.30(2H,m), 4.30-4.80(2H,br), 7.00(1H,dd,J=8.4,1.5Hz), 7.05(1H,d,J=1.5Hz)1 7.30(1H,d,J=8.4Hz), 7.38(1H,s), 8.00(1H,d,J=7.3Hz), 8.43(1H,br.s), 11.45(1H,br.s), 11.49(1H,br.s). MS (FAB) m/z: 452(M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
(3) 5-Methyl-2-indolecarboxylic acid: 1H NMR (DMSO-d6) delta: 2.36 (3H, s), 6.98 (1H, dd, J=1.0, 2.0 Hz), 7.04-7.08 (1H, m), 7.30-7.33 (1H, m), 7.40 (1H, s), 11.6 (1H, br-s), 12.9 (1H, br-s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
15% | With triethanolamine; (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; In N,N-dimethyl-formamide; | EXAMPLE 48 5-Methyl-1H-indole-2-carboxylic acid-(5-ethanesulfonyl-2-hydroxy-phenyl)-amide TEA (0.28 mL, 2.0 mmole) was added to a solution of <strong>[10241-97-1]5-methyl-1H-indole-2-carboxylic acid</strong> (175 mg, 1.0 mmole), 2-amino-4-ethanesulfonyl-phenol (201 mg, 1.0 mmole), and BOP (442 mg, 1.0 mmole) in DMF (2.0 mL). The reaction mixture was shaken at room temperature overnight and then diluted with 1N hydrochloric acid (20 mL). The resulting precipitate was filtered off and washed with water. The residue was triturated with EtOAc (40 mL), the solvent was dried over magnesium sulfate, filtered, and reduced in volume while slowly adding hexanes until crystallization began. The crystalline product was filtered off and air-dried to afford the title compound as a brown powder (55 mg, 15percent yield). AP-/MS=359; AP-/MS=357. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In tetrahydrofuran; at 20℃; | General procedure: To a solution of <strong>[10241-97-1]5-methyl-1H-indole-2-carboxylic acid</strong> (20) (263mg, 1.50mmol) in THF (7mL) were added 2-(piperidin-4-yl)ethanol (213mg, 1.65mmol), 1-hydroxybenzotriazole (HOBt, 101mg, 0.750mmol), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDAC) hydrochloride (316mg, 1.65mmol), followed by stirring at room temperature for 14h. The reaction mixture was partitioned between ethyl acetate and 0.5M aqueous hydrochloric acid. The organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and then concentrated in vacuo. The residue was recrystallized from ethyl acetate/acetonitrile (5mL/2mL) to give 3 (365mg, 85.0percent) as a beige powder. |
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; | Example 24 To a solution of 1800 mg of <strong>[10241-97-1]5-methylindole-2-carboxylic acid</strong> and 1500 mg of 2-methyl-1-(piperidin-4-yl)-2-propanol in 25 mL of DMF were added 2100 mg of 1-ethyl-3-(dimethylaminopropyl)carbodiimide hydrochloride and 1500 mg of 1-hydroxybenzotriazole, followed by stirring at room temperature for 1 day. 0.5M aqueous hydrochloric acid was added to the reaction liquid, followed by extraction with ethyl acetate. The organic layer was washed with 0.5M aqueous sodium hydroxide solution and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography [chloroform:methanol = 1:0-10:1], and then crystallized from a mixture of ethyl acetate/diisopropyl ether to obtain 2140 mg of 2-methyl-1-{1-[(5-methyl-1H-indol-2-yl)carbonyl]piperidin-4-yl}propan-2-ol as a white crystal. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With thionyl chloride; for 0.25h;Reflux; Inert atmosphere; | General procedure: Commercial indole-2-carboxylic acid was dissolved in thionyl chloride (1.5 mL/mmol) and the suspension was boiled for 15 min, during which time typically a dark green solution was formed. Excess thionyl chloride was removed under reduced pressure and the solid residue was suspended in toluene and the suspension was evaporated to dryness (toluene treatment was repeated three times). The green-grayish solid residues were used without further purification. | |
With oxalyl dichloride; In dichloromethane; N,N-dimethyl-formamide; at 0 - 20℃; | A vial was charged with 5-methyl-lH-indole-2-carboxylic acid (175 mg, 1.00 mmol, 1.00 equiv), DCM (10 mL) and oxalyl chloride (381 mg, 3.00 mmol, 3.00 equiv). N,N- Dimethylformamide (0.05 mL) was added at 0 °C. The resulting solution was stirred for 4 h at room temperature and concentrated under reduced pressure to provide 194 mg (crude) of 5- methyl-lH-indole-2-carbonyl chloride |
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