Structure of 18653-98-0
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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. : | 18653-98-0 |
Formula : | C16H20N2O2 |
M.W : | 272.34 |
SMILES Code : | OC1=CC=CC=C1CNCCNCC2=CC=CC=C2O |
MDL No. : | MFCD00058922 |
InChI Key : | MLFXJCXPSODAIS-UHFFFAOYSA-N |
Pubchem ID : | 199210 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H303-H315-H319-H335 |
Precautionary Statements: | P261-P264-P271-P280-P302+P352-P304+P340+P312-P305+P351+P338-P332+P313-P337+P313-P362+P364-P403+P233-P405-P501 |
Num. heavy atoms | 20 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 7 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 4.0 |
Molar Refractivity | 79.97 |
TPSA ? Topological Polar Surface Area: Calculated from |
64.52 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.75 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.75 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.67 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.72 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.41 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.26 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.24 |
Solubility | 0.156 mg/ml ; 0.000571 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.76 |
Solubility | 0.0473 mg/ml ; 0.000174 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-5.49 |
Solubility | 0.000887 mg/ml ; 0.00000326 mol/l |
Class? Solubility class: Log S scale |
Moderately 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) |
Yes |
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 |
-6.01 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 |
1.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.58 |
* 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 |
---|---|---|
84% | With sodium tetrahydroborate; In methanol; at 30℃; for 0.5h; | General procedure: Sodium borohydride (2.0 equiv) was added to a stirring suspension of the imino-compound (1A-6A) (1.0 equiv) in methanol (20 mL) at room temperature. After 30 min the reaction mixture was poured on ice and the resulting suspension filtered. The obtained solid was washed with water and n-hexane to give the corresponding amino-derivate (1B-6B) in high yields. Some compounds have been already synthesized and characterized and our results (Supplementary data) are in complete agreement with those reported in the literature. |
70% | With sodium tetrahydroborate; In N,N-dimethyl-formamide; | The ethylenediamine (0.003 mol), dissolved in 20 cm3 ofmethanol, was added dropwise to salysilaldehyde (1) (0.003 mol) in 150 cm3 of methanol. After the addition, the reaction mixture was stirred to room temperature, and 0.006 mol of sodium borohydride in 15 mL of dimethylformamide was added in portions with stirring. The yellow colour of the reaction mixture disappears with addition of all portion of sodium borohydride, indicated to completionof hydrogenation. When the reduction was completed,mixture was poured in cold distilled water. Formed white precipitate was washed with water and diethyl ether, andthen dried over anhydrous sodium sulphate. |
With methanol; sodium tetrahydroborate; for 0.25h;Reflux; | General procedure: General procedure for synthesis of BC-1209. 2-Hydroxybenzaldehyde (0.01 mol, 1.22 g) were added to a solution of ethylenediamine (0.005 mol, -350 ul) in anhydrous ethanol (20 ml). The resulting solution was heated and stirred for 10 min until the precipitation of the relevant Schiff base. The Schiff bases were filtered off, and washed with cold ethanol. The Schiff base was then added to 30 ml absolute methanol. A 10% solution of sodium borohydride (0.02 mol) was dissolved in absolute methanol and added to the Schiff base. When the dropwise addition of sodium borohydride was complete, the reaction solution was refluxed for an additional 15 min. Solvent was then removed through rotary evaporation and 40 ml cold water was added to liberate the secondary amine. The precipitation of BC-1209 were collected, washed with water and dried, followed by recrystallization from ethyl acetate. |
With sodium tetrahydroborate; In methanol; at 20℃; for 2h; | General procedure: Schiff base ligand can be easily converted to tetrahydro-Schiff base ligand by the hydrogenation ofCH=N to CH2-NH in presence of NaBH4 in MeOH.Tetrahydro-Schiff base ligands were prepared as follows:0.01 mol of SalenH2, SalhexenH2 or SalphenH2was dissolved in 60 mL of methanol, followed by theaddition of 0.011 mol of NaBH4 at ambient temperature.After stirring for 2 h, the solvent was removedunder reduced pressure. The solid product was furtherwashed with distilled water and recrystallized fromethanol, and the obtained materials were denoted as[H4]SalenH2, [H4]SalhexenH2 and [H4]SalphenH2,respectively. The 1H NMR spectra of [H4]SalenH2,[H4]SalhexenH2 and [H4]SalphenH2 are also shown inFig. 1. 1H NMR (CDCl3), δ, ppm: [H4]SalenH2 -7.25-6.78 (8H, m, Ar-H), 3.99 (4H, s, N-CH2CH2-N), 2.84 (4H, s, CH2-NH) (Fig. 1b); | |
With hydrogenchloride; sodium tetrahydroborate; In methanol; water; | The di-Schiff base ligand from 1,3-propanediamine and salicylaldehydewas synthesized by a reported method [17]. 5 mmol of1,3-propanediamine (0.42 mL) was mixed with 10 mmol of the salicylaldehyde(1.04 mL) in methanol (30 mL). The resulting solutionwas refluxed for ca. 2 h and allowed to cool. Then 30 mL (5 mmol)of this prepared yellow methanolic ligand solution (H2L1) wascooled to 0 C, and solid sodium borohydride (570 mg, 15 mmol)was added to this methanol solution with stirring. After completionof addition, the resulting solution was acidified with concentratedHCl (12 mL) and then evaporated to dryness [18]. Thereduced Schiff base ligand H2L1R was extracted from the solid masswith methanol, and this colorless methanol solution (ca. 30 mL)was added to a methanolic solution (10 mL) of Cu(ClO4)26H2O(1.852 g, 5 mmol) to prepare the ‘‘metalloligand” [CuL1R] | |
With hydrogen; In methanol; at 25℃; under 1520.1 Torr; for 24h; | First, 100 mL of methanol in which 3.5 × 10 -1 mmol of Compound II was dissolved was placed in a round bottom flask 101. Next, while supplying H 2 from the hydrogen cylinder of the hydrogen supply apparatus to the hydrogen supply module 1 at 2 atm, the mixture was stirred for 24 hours in an environment at an indoor temperature of 25 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With 1-hexadecyl-1H-imidazol-3-ium oxalate; In water; at 90℃; for 0.166667h; | General procedure: To a 100 cm3 round-bottomed flask containing 15 cm3 ofwater were added 0.30 g of corresponding bis-secondaryamine (1.1 mmol), 0.13 g of paraformaldehyde (4.4 mmol,4 equivalent), and 2.5 mmol% of catalyst. The flask wasattached to a reflux condenser and heated under atmosphericconditions in an oil bath at 90 C for 10 min.Thereafter the flask was cooled in an ice bath and 15 cm3of cold water was added. The resulting solid product was collected by filtration and dried at room temperature.Recrystallization from an appropriate solvent gave pure 2e. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With methanol; sodium tetrahydroborate; potassium hydroxide; In dichloromethane; at 0℃; | General procedure: The Schiff base (2.27 mmol) dissolved in dichloromethane (10 mL). Reaction mass cooled at 00C and 2-3 drops of conc. KOH solution added. The solution of NaBH4 (2.0 mmol) in methanol added dropwise. Reaction mass stirred for 4-5 h until the yellow colour disappeared. Reaction monitored on TLC. After completion of reaction solvent distilled and cold water (10 mL) added to dissolve residue. pH adjusted to 4-5 by addition of dilute HCl. The white solid filtered, washed with water dried. 2, 2’-[ethane-1, 2-diylbis(azanediyl methylene)]diphenol [RSB01]m.p.: 1180C; Colour: white; MS [M+2]: 273.99; FTIR(KBr cm-1): 3490, 3463, 3363, 3052, 2942, 2852, 2593, 1602, 1479, 1417, 1353, 1268, 1189, 1126, 1074, 960, 815, 757, 626; 1H NMR (300 MHz, DMSO-d6) δ: 2.481 (m, 4H), 3.770 (s, 4H), 5.031 (s, 2H), 6.658-6.686 (m, 4H), 7.01-7.06 (m, 4H), 13.335 (s, 2H); Elemental analysis [C16H20N2O2]: observed (Calculated): C 70.63% (70.56%), H 7.31% (7.40%), N 10.34% (10.29%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20.1% | With sodium tris(acetoxy)borohydride; In 1,1-dichloroethane; at 20℃; for 18h; | Placed N, N'-Bis (2-hydroxybenzyl) ethylenediamine (0.1 g,0..367 mmol) in a 100 ml round-bottom flask equipped with a stirrer under nitrogen. The solid was dissolved in 8 ml of dichloroethane, followed by addition of [N-{ethyl-2-diethoxy}-2- imidazolecarboxaldehyde] (0.165 g, 0.775 mmol) and sodium triacetoxyborohydride (0.178 g, 0.845 mmol). The solution was stirred at room temperature for 18 hours. The solution was then vacuumed down to residue. The residue was passed through a silca gel column using 0-20% methanol/methylene chloride as the solvents, yielding 0.049 g, 20. 1 % yield.lHNMR ((CDC13), 300 MHz): 1.10 (t, 12H), 2.10 (s, 8H), 2.77 (s, 2H), 3.34 (m, 4H), 3.58 (m, 4H), 3.77 (s, 2H), 3.84 (d, 2H), 4.45 (t, 2H), 6.72 (t, 2H), 6.85 (m, 8H), 6.96 (s, 2H), 7.13 (t, 2H). ES/MS = 666-668: expected 668. |
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