Structure of 124-30-1
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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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Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 124-30-1 |
Formula : | C18H39N |
M.W : | 269.51 |
SMILES Code : | CCCCCCCCCCCCCCCCCCN |
MDL No. : | MFCD00008159 |
InChI Key : | REYJJPSVUYRZGE-UHFFFAOYSA-N |
Pubchem ID : | 15793 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H303-H304-H315-H318-H373-H410 |
Precautionary Statements: | P260-P264-P273-P280-P301+P310-P302+P352-P305+P351+P338+P310-P312-P331-P332+P313-P391-P405-P501 |
Class: | 9 |
UN#: | 3077 |
Packing Group: | Ⅲ |
Num. heavy atoms | 19 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 16 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 91.35 |
TPSA ? Topological Polar Surface Area: Calculated from |
26.02 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
5.12 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
4.3 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
6.21 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
4.93 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
6.3 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
5.37 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.16 |
Solubility | 0.185 mg/ml ; 0.000686 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.56 |
Solubility | 0.00743 mg/ml ; 0.0000276 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-6.79 |
Solubility | 0.0000437 mg/ml ; 0.000000162 mol/l |
Class? Solubility class: Log S scale |
Poorly 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) |
Yes |
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) |
Yes |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-4.89 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
1.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
1.0 |
Egan? Egan (Pharmacia) filter: implemented from |
1.0 |
Muegge? Muegge (Bayer) filter: implemented from |
2.0 |
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<2.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.3 |
* 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 N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 2 - 20℃;Inert atmosphere; | 4-{5-[Bis-(2-chloro-ethyl)-amino]-l-methyl-lH-benzoimidazol-2-yl}-N-octadecyl-butyramide (<strong>[3543-75-7]bendamustine</strong> Cjg amide): A 250 mL three neck round bottom flask equipped with a stir bar, thermocouple, cooling bath, 60 mL pressure equalizing dropping funnel and nitrogen in/outlet was charged with 10.0 g (25.3 mmol) of <strong>[3543-75-7]<strong>[3543-75-7]bendamustine</strong> hydrochloride</strong>, 10.6 g (27.8 mmol) of HATU and 100 mL of Nu,Nu-dimethylfomramide (DMF). To this stirred yellow solution was added 4.41 mL (3.27 g, 25.3 mmol) of Nu,Nu-diisopropylethyelamine (DIPEA). An exotherm to 27.1C was noted and the solution became a darker yellow. The reaction was cooled to 2.0C where a suspension of 6.2 mL (4.59 g, 35.5 mmol) of DIPEA, 7.65 g (25.6 mmol) of octadecyl amine in 0 mL of DMF was added via pipet. Once addition was complete the reaction became very thick and difficult to stir. It was warmed to room temperature and the magnetic stir bar was replaced with an overhead stirrer. The batch was stirred at RT overnight after which time an in process analysis indicated the reaction was complete. The batch was quenched onto 300 mL of DI water and extracted with dichloromethane (2 X 150 mL). The organic phases were combined, washed with 10% sodium hydrogen phosphate (1 X 300 mL), 8% aqueous sodium bicarbonate (1 X 300 mL) and brine (1 X 300 mL) before drying over sodium sulfate, filtering and concentrating to dryness in vacuo. The residue was purified by chromatography using lOOg of silica gel 60, 230-400 mesh, eluting with 1% MeOH/MDC (2 L), 2.5 % MeOH/MDC (1L) and 5% MeOH/MDC (1L) collecting -100 mL fractions. The product containing fractions were combined and concentrated to dryness in vacuo to yield 5.1 1 g (8.38 mmol, 33%) of the desired product as a white solid with an HPLC purity of 90.9A%. The major impurity was shown to be the C-16 amide which results from an impurity in the starting amine. XH NMR (400 MHz, DMSO-d6) delta 7.72 (s, b, 1H), 7.33 (d, J= 8.84 Hz, 1H), 6.91 (d, J= 2.22 Hz, 1H), 6.80 (dd, J= 2.36, 8.84 Hz), 3.71 (s, 8H), 3.70 (s, 3H), 3.01 (q, J= 6.8, 12.68, 2H), 2.79 (t, J= 7.44 Hz, 2H), 2.18 (t, J= 7.36 Hz, 2H), 1.97 (m, 2H), 1.36 (m, 2H), 1.28 (s, b, 30H), 0.85 (t, J= 6.32 Hz, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75.3% | In ethanol; for 12h;Reflux; | n-Octadecylamine (538 mg,1.2 mmol)was added into a solutionof <strong>[6492-86-0]4-amino-1,8-naphthalic anhydride</strong> (213 mg,1.0 mmol) in ethanol(30 mL). The reaction mixture was stirred at reflux for 12 h. Afterthe mixture was cooled to room temperature, the solvent wasremoved under reduced pressure. The crude product was purifiedvia column chromatography (silica gel, dichloromethane) to give350 mg of 2a as a yellow solid in 75.3% yield. M.p. 132-133 C; 1HNMR (500 MHz, CDCl3): delta 8.59 (dd, 1H, J 1.0 Hz), 8.41 (d, 1H,J 8.5 Hz), 8.10 (dd, 1H, J 1.0 Hz), 7.65 (dd, 1H,J 7.0 Hz J 7.5 Hz), 6.88 (d, 1H, J 8.0 Hz), 4.95 (s, 2H), 4.15 (t, 2H,J 7.3 Hz), 1.71 (m, 2H), 1.41 (m, 2H), 1.26 (m, 28H), 0.88 (t, 3H,J 7.0 Hz); 13C NMR (125 MHz, CDCl3): delta 164.6, 164.0, 148.9, 133.7,131.4, 129.8, 126.7, 125.0, 123.3, 120.1, 112.1, 109.6, 77.3, 77.0, 76.8,40.3, 31.9, 29.7, 29.7, 29.6, 29.6, 29.5, 29.4, 28.2, 27.2, 22.7, 14.1; EPIMSC30H44N2O2 ([M+H]+): calcd 465.3, found 465.5; Elem. anal. forC30H44N2O2: calcd C 77.54, H 9.54, O 6.89; found C 77.34, H 9.76, O6.92%. |