Structure of 90942-47-5
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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. : | 90942-47-5 |
Formula : | C9H11Cl2NO2 |
M.W : | 236.10 |
SMILES Code : | Cl.COC(=O)C1=C(Cl)C=CC(CN)=C1 |
MDL No. : | MFCD16876981 |
Boiling Point : | No data available |
InChI Key : | RVCZOTOWWCOGCQ-UHFFFAOYSA-N |
Pubchem ID : | 66524840 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302+H312+H332-H315-H319-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.22 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 57.37 |
TPSA ? Topological Polar Surface Area: Calculated from |
52.32 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.04 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.24 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.23 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.96 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.69 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.71 |
Solubility | 0.462 mg/ml ; 0.00196 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.77 |
Solubility | 0.404 mg/ml ; 0.00171 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.14 |
Solubility | 0.171 mg/ml ; 0.000724 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) |
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 |
-6.29 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 |
0.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
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) |
1.77 |
* 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 |
---|---|---|
Preparation 24Methyl 2-chloro-5-[(2,2-dimethylpropanoylamino)methyl]benzoateTo a thermally controlled reactor, add <strong>[90942-47-5]methyl 5-(aminomethyl)-2-chlorobenzoate hydrochloride</strong> (700 g, 3.51 mol, 1.0 equiv), dichloromethane (4.9 L), and N,N-diisopropylethylamine (1.71 L, 9.82 mol, 2.8 equiv). Add pivaloyl chloride (515 mL, 4.21 mol, 1.2 equiv) dropwise at such a rate that the internal temperature does not exceed 21 C. Upon completion of the addition, stir the reaction mixture at room temperature for one hour. Quench the reaction mixture with saturated aqueous sodium bicarbonate (10 L). Extract the mixture with dichloromethane (2×1 L), combine the organic extracts, dry over sodium sulfate, filter, and concentrate under reduced pressure to give an oil, (1.1 kg) carried on crude without further purification. MS (m/z) (35C1/37C1) 284/286 (M+1) | ||
2 g | With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 26℃; for 1.0h; | To a solution of <strong>[90942-47-5]methyl 5-(aminomethyl)-2-chlorobenzoate hydrochloride</strong> (1.80 g, 6.00 mmol) in CH2C12 were added DIPEA (3.096 g, 2.4 mmol ) followed by pivaloyl chloride (1.2 mL, 9.0 mmol) at 0-5C and the reaction mixture was stirred at rt for lh before it was quenched with water and was extracted with chloroform. The organic layer was separated, dried, filtered and concentrated to afford 2.0 g of the title product. 1H NMR (300 MHz, DMSO d6): delta 8.16 (m, 1H), 7.65 (s, 1H), 7.53 (d, / = 8.4 Hz, 1H), 7.41 (d, / = 8.4 Hz, 1H), 4.25 (d, / = 5.7 Hz, 2H), 3.85 (s, 3H), 1.15 (s, 9H). |
2 g | With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 22 - 26℃; for 2.0h; | General procedure: To a solution of ethyl 3-(aminomethyl)-6-chloro-2-fluorobenzoate (70 mg, 0.3 mmol) in THF (3 mL) were added Et3N (0.105 mL, 0.76 mmol) and pivaloyl chloride (38 muL, 0.31 mmol). The reaction mass was stirred at rt for 2 h, diluted with EtOAc and was washed with water, and brine. The organic layer was separated, dried, filtered and concentrated to afford 70 mg of the title product. 1H NMR (300 MHz, DMSO-d6): delta 8.15 (br t, 1H), 7.43-7.35 (m, 2H), 4.38 (q, J=7.2 Hz, 2H), 4.26 (d, J=5.7 Hz, 2H), 1.30 (t, J=6.9 Hz, 3H), 1.11 (s, 9H). 10301] The title compound was prepared following the procedure described in step-2 of Intermediate-2 using <strong>[90942-47-5]methyl 5-(aminomethyl)-2-chlorobenzoate hydrochloride</strong> (1.80 g,6.00 mmol), DIPEA (3.096 g, 2.4 mmol) and pivaloyl chloride (1.2 mE, 9.0 mmol) in THF (20 mE) to afford 2.0 g of the title product. 1H NMR (300 MHz, DMSO d5): 8.16 (m, 1H), 7.65 (s, 1H), 7.53 (d, J=8.4 Hz, 1H), 7.41 (d, J=8.4 Hz, 1H),4.25 (d, J=5.7 Hz, 2H), 3.85 (s, 3H), 1.15 (s, 9H). |
2 g | With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 20℃; for 2.0h; | To a solution of <strong>[90942-47-5]methyl 5-(aminomethyl)-2-chlorobenzoate hydrochloride</strong> (1.80 g, 6.00 mmol) in THF (20 mL) were added DIPEA (3.096 g, 24.0 mmol) and pivaloyl chloride (1.2 mL, 9.0 mmol). The reaction mass was stirred at rt for 2 h, diluted with EtOAc and was washed with water, and brine. The organic layer was separated, dried, filtered and concentrated to afford 2.0 g of the title product. 1H NMR (300 MHz, DMSO-i): delta 8.16 (m, 1H), 7.65 (s, 1H), 7.53 (d, J = 8.4 Hz, 1H), 7.41 (d, J = 8.4 Hz, 1H), 4.25 (d, J = 5.7 Hz, 2H), 3.85 (s, 3H), 1.15 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80 mg | With dihydrogen peroxide; In water; ethyl acetate; at 22 - 26℃; for 2.0h; | A solution of methyl 5-(((ierf-butoxycarbonyl)amino)methyl)-2-chlorobenzoate (100 mg, 0.334 mmol) in EtOAc saturated with HC1 solution (1 mL) was stirred at rt for 2 h. The reaction mixture was concentrated and was triturated with pentane to afford 80 mg of the title product. H NMR (300 MHz, DMSO d6): delta 8.20 (br s, 3H), 7.95 (s, 1H), 7.67 (s, 2H), 4.00 (s, 2H), 3.88 (s, 3H). |
80 mg | With hydrogenchloride; In ethyl acetate; at 22 - 26℃; for 2.0h; | A solution of methyl 5-(((iert-butoxycarbonyl)amino)methyl)-2-chlorobenzoate (100 mg, 0.334 mmol) in EtOAc saturated with HC1 (1 mL) was stirred at rt for 2 h. The reaction mixture was concentrated and was triturated with pentane to afford 80 mg of the title product. 1H NMR (300 MHz, DMSO d6): delta 8.20 (br s, 3H), 7.95 (s, 1H), 7.67 (s, 2H), 4.00 (s, 2H), 3.88(s, 3H). |
80 mg | With hydrogenchloride; In ethyl acetate; at 22 - 26℃; for 2.0h; | A solution of methyl 5-(((tert-butoxycarbonyl)amino)methyl)-2-chlorobenzoate (100 mg, 0.334 mmol) in EtOAc saturated with HCl (1 mL) was stirred at rt for 2 h. The reaction mixture was concentrated and was triturated with pentane to afford 80 mg of the title product. 1H NMR (300 MHz, DMSO d6): delta 8.20 (br s, 3H), 7.95 (s, 1H), 7.67 (s, 2H), 4.00 (s, 2H), 3.88 (s, 3H). |
80 mg | With hydrogenchloride; In ethyl acetate; at 20℃; for 2.0h; | A solution of methyl 5-(((ieri-butoxycarbonyl)amino)methyl)-2-chlorobenzoate (100 mg, 0.334 mmol) in EtOAc saturated with HCl (1 mL) was stirred at rt for 2 h. The reaction mixture was concentrated and was triturated with pentane to afford 80 mg of the title product. 1H NMR (300 MHz, DMSO-i): delta 8.20 (br s, 3H), 7.95 (s, 1H), 7.67 (s, 2H), 4.00 (s,2H), 3.88 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
250 mg | With N-ethyl-N,N-diisopropylamine; In dichloromethane; at -50 - 26℃; for 2.0h; | To a solution 1-methylcyclopropanecarboxylic acid (140 mg, 1.39 mmol) in dichloromethane (5.0 mL) were added oxalyl chloride (211 mg, 1.6 mmol) and a drop of DMF. The reaction mass was stirred at rt for 2 h and was added to the solution of methyl 5-(aminomethyl)-2- chlorobenzoate hydrochloride (200 mg, 0.911 mmol) and DIPEA (183 mg, 1.36 mmol) in CH2CI2 (3 mL) at -50C. The reaction mixture was stirred at rt for 2 h. The reaction mixture was quenched with water and was extracted with CHCI3. The organic layer was separated, dried and concentrated to afford 250 mg of the title product. XH NMR (300 MHz, DMSO d6): delta 8.19 (m, 1H), 7.65 (s, 1H), 7.52 (d, / = 8.1Hz, 1H), 7.41 (d, / = 8.1Hz, 1H), 4.26 (d, / = 5.7 Hz, 2H), 3.85 (s, 3H), 1.27 (s, 3H), 0.94 (m, 2H), 0.53 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
250 mg | With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 0 - 26℃; for 2.0h; | To a solution of <strong>[90942-47-5]methyl 5-(aminomethyl)-2-chlorobenzoate hydrochloride</strong> (step-2 of intermediate-4, 200 mg, 0.911 mmol) in THF were added DIPEA (183 mg, 1.36 mmol) and 1- isobutyryl chloride (145 mg, 1.36 mmol) at 0-5C. The reaction mass was stirred at rt for 2 h before it was quenched with water and was extracted with CHCI3. The organic layer was separated, dried, filtered and concentrated to afford 250 mg of the title product. XH NMR (300 MHz, DMSO d6): delta 8.36 (m, 1H), 7.65 (s, 1H), 7.53 (d, J = 8.7 Hz, 1H), 7.41 (d, J = 6.3 Hz, 1H), 4.26 (d, / = 5.7 Hz, 2H), 3.85 (s, 3H), 2.37-2.44 (m, 1H), 1.02 (d, J = 6.0 Hz, 6H). |
1.2 g | With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 22 - 26℃; for 2.0h; | To a solution of <strong>[90942-47-5]methyl 5-(aminomethyl)-2-chlorobenzoate hydrochloride</strong> (2.50 g,10.59 mmol) in THF (20 mL) were added DIPEA (4.78 g, 37.07 mmol) andisobutyryl chloride (1.70 g, 15.89 mmol). The reaction mass was stirred at RT for 2 h. After completion of the reaction, the reaction mixture was diluted with EtOAc, washed with water and brine, dried over Na2 SO4 and concentrated to afford 1.2 g of the desired product. ?H NIVIR (300 IVIHz, DMSO-d6): 8.35 (t, 1H), 7.66 (s, 1H),7.55-7.52 (d, J= 8.1 Hz, 1H), 7.43-7.40 (d, J 8.1 Hz, 1H), 4.26 (d, J 5.7 Hz, 2H),3.85 (s, 3H), 2.44 (m, 1H), 1.02 (d, J= 6.9 Hz, 6H); MS [M+H]: 270.12. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
200 mg | With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 22 - 26℃; for 12.0h; | A solution of (iS,5S)-3-oxabicyclo[3.1.0]hexane-l-carboxylic acid (200 mg, 1.72 mmol), <strong>[90942-47-5]methyl 5-(aminomethyl)-2-chlorobenzoate hydrochloride</strong> (Intermediate-5, step-3; 488 mg, 2.06 mmol) benzotriazole-l-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (1.91 g, 4.31 mmol), DIPEA (665 mg, 5.16 mmol) in DMF (10 mL) was stirred at rt for 12h. Then the reaction mixture was diluted with water and was extracted with EtOAc. The organic layer was washed with brine, separated, dried, filtered and concentrated. The residue was purified by column chromatography to afford 200 mg of the title product. 1H NMR (300 MHz, DMSO d6): delta 8.18 (br t, 1H, NH), 7.67 (s, 1H), 7.54-7.52 (d, / = 7.8 Hz, 1H), 7.44-7.42 (d, / = 8.1 Hz, 1H), 4.29-4.27 (d, / = 6.3 Hz, 1H), 3.86- 3.63 (m, 4H), 2.05 (m, 1H), 1.34- 1.31 (m, 1H), 0.85- 0.81 (m ,lH). |
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