Structure of 325775-44-8
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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. : | 325775-44-8 |
Formula : | C9H18N2O2 |
M.W : | 186.25 |
SMILES Code : | O=C(N1CC(CN)C1)OC(C)(C)C |
MDL No. : | MFCD01861762 |
InChI Key : | XSJPKMUFBHSIRA-UHFFFAOYSA-N |
Pubchem ID : | 10679125 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P301+P312-P302+P352-P304+P340-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.89 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 54.49 |
TPSA ? Topological Polar Surface Area: Calculated from |
55.56 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.3 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.2 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.43 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.56 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.12 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.72 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.86 |
Solubility | 25.9 mg/ml ; 0.139 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.93 |
Solubility | 22.1 mg/ml ; 0.119 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.76 |
Solubility | 32.1 mg/ml ; 0.173 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 |
-7.29 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 |
1.0 |
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) |
2.1 |
* 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 |
---|---|---|
18 g | With hydrogenchloride; In ethanol; water; | To a solution of l-Boc-3-(aminomethyl)-azetidine (15.5 g, 82.9 mmol) in EtOH (250 mL) was slowly added aq. HCl (1.0 M, 83 mL). The solvent was removed in vacuo at 38 °C, providing the hydrochloride salt of the amine as a white solid (18.0 g). |
18 g | With hydrogenchloride; In ethanol; water; | To a solution of l-Boc-3-(aminomethyl)-azetidine (15.5 g, 82.9 mmol) in EtOH (250 mL) was slowly added aq. HC1 (1.0 M, 83 mL). The solvent was removed in vacuo at 38 °C, providing the hydrochloride salt of the amine as a white solid (18.0 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 12h;Inert atmosphere; | [000381] Synthesis of tert-butyl 3-((11-oxo-10, 11-dihydrodibenzo [b,J] [1,4j thiazepine-8-carboxamido) methyl) azetidine-1-carboxylate (461): To a stirred solution of compound 6 (600 mg, 2.21 mmol) in DMF (5 mL) under argon atmosphere were added EDCI.HC1 (634 mg, 3.32 mmol), HOBt (435 mg, 3.32 mmol), tert-butyl 3-(aminomethyl) azetidine-1-carboxylate460 (453 mg, 2.43 mmol) and diisopropyl ethyl amine (1.14 mL, 6.64 mmol) at RT and stirred for 12 h. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was diluted with water (25 mL) and extracted with EtOAc (2 x 50 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo to obtain the crude. The crude was purified through silica gel column chromatography using 5% MeOH/ CH2C12 to afford compound 461 (600 mg, 61%) as an off-white solid. TLC: 10% MeOH/ CH2C12 (R 0.6); 1H NMR (DMSO-d6, 400 MHz): oe 10.76 (s, 1H), 8.64 (t, J= 5.6 Hz, 1H), 7.71-7.64 (m, 3H), 7.59-7.43 (m, 4H), 3.84 (t, J 7.0 Hz, 2H), 3.66-3.50 (m, 2H), 3.41 (t, J= 6.3 Hz, 2H), 2.72-2.64 (m, 1H), 1.33 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81.9% | With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 70℃; | Step 1: preparation of tert-butyl 3-(((2-chloro-thieno[2,3-d]pyrimidin-4-yl)amino) methyl)azetidine-1-carboxylate (0278) (0279) 2,4-Dichloro-thieno[2,3-d]pyrimidine (300 mg, 1.46 mmol) and tert-butyl 3-(aminomethyl)azetidine-1-carboxylate (272 mg, 1.46 mmol) were dissolved in tetrahydrofuran (25 mL), followed by the addition of N,N-diisopropylethylamine (258 mg, 2 mmol). The reaction solution was reacted at 70°C overnight, and then concentrated. The residue was added with water (50 mL), and extracted with ethyl acetate (20 mL × 3). The organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by silica gel column chromatography (eluent: n-hexane: ethyl acetate = 1: 5) to give a white solid (425 mg). Yield: 81.9percent. MS (ESI, m/z): [M+H]+: 355.2. |
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