Structure of 3616-59-9
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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. : | 3616-59-9 |
Formula : | C10H21NO3 |
M.W : | 203.28 |
SMILES Code : | CCOC(OCC)CN1CCOCC1 |
MDL No. : | MFCD00034483 |
InChI Key : | SZCDHXBTGQLOBZ-UHFFFAOYSA-N |
Pubchem ID : | 248492 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H319 |
Precautionary Statements: | P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 6 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 58.14 |
TPSA ? Topological Polar Surface Area: Calculated from |
30.93 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.83 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.49 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.34 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.2 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.35 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.04 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.01 |
Solubility | 19.7 mg/ml ; 0.097 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.71 |
Solubility | 39.7 mg/ml ; 0.195 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.59 |
Solubility | 5.23 mg/ml ; 0.0257 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) |
Yes |
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 |
-7.19 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 |
1.0 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) |
2.45 |
* 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 |
---|---|---|
56% | With potassium carbonate; at 120℃; for 16.0h; | Example 28 - Preparation of Cmpd 23; [0206] A useful scheme for the preparation of compounds of the type of Cmpd 23 is provided in Scheme 2 following. Scheme 2Intermediate 7 Intermediate 8Cmpd 23 Intermediate 9[0207] A detailed description of the preparation of Intermediates 7-9 and Cmpd 23 follows. Preparation of Intermediate 7Intermediate 7[0208] A mixture of 2-bromoacetaldehyde diethyl acetal (4.5 g, 22.9 mmol), morpholine (2.0 g, 22.9 mmol) and K2C03 (6.34 g, 45.9 mmol, 2 eq) was stirred at 120 C for 16 h. The reaction mixture was cooled to RT, diluted with water (50 mL) and extracted with DCM (3 x 50 mL). The organic layer was washed with saturated aqueous NaHC03 (50 mL), brine (50 mL), dried over Na2S04, filtered and concentrated to get crude a residue. The crude compound was purified by column chromatography over silica gel (100-200 mesh) by using a gradient mixture of 0-50% EtOAc-hexane as the eluent to afford Intermediate 7 (2.6 g, 56%) as a pale yellow liquid. 1H NMR: (CDC13) delta 4.64 (t, J= 5.3 Hz, 1H), 3.63-3.70 (m, 6H), 3.50-3.58 (m, 2H), 2.52-2.55 (m, 6H), 1.20 (t, J= 7.0 Hz, 6H); TLC: 60% EtOAc in hexane: Rf: 0.50. |
56% | With potassium carbonate; at 120℃; for 16.0h; | A mixture of 2-bromoacetaldehyde diethyl acetal (4.5 g, 22.9 mmol), morpholine (2.0 g, 22.9 mmol) and K2CO3 (6.34 g, 45.9 mmol, 2 eq) was stirred at 120C. for 16 h. The reaction mixture was cooled to RT, diluted with water (50 mL) and extracted with DCM (350 mL). The organic layer was washed with saturated aqueous NaHCO3 (50 mL), brine (50 mL), dried over Na2SO4, filtered and concentrated to get crude a residue. The crude compound was purified by column chromatography over silica gel (100-200 mesh) by using a gradient mixture of 0-50% EtOAc-hexane as the eluent to afford Intermediate 7 (2.6 g, 56%) as a pale yellow liquid. 1H NMR: (CDCl3) delta 4.64 (t, J=5.3 Hz, 1H), 3.63-3.70 (m, 6H), 3.50-3.58 (m, 2H), 2.52-2.55 (m, 6H), 1.20 (t, J=7.0 Hz, 6H); TLC: 60% EtOAcin hexane: Rf: 0.50. |
14% | With potassium carbonate; In N,N-dimethyl-formamide; at 120℃; for 5.0h; | Synthesis of compound 62.2. Morpholine (2.0g, 2.19mmol, l .Oeq), bromoacetaldehyde diethyl acetal (4.5g, 2.54mmol, 1.16eq) and dry K2CO3 (6.04g, 4.38mmol, 2.0 eq) were mixed in dry dimethylformamide and heated at 120 C for 5h. After completion of reaction, reaction mixture was diluted with ethyl acetate (200ml) and washed with water (200ml x2) and then with brine (100ml). Organic layer was dried over sodium sulphate and concentrated under reduced pressure at 45C. Crude was purified by column chromatography to afford compound 62.2 (0.650g, 14%). 1H NMR (400 MHz, CDC13): delta 4.660-4.686 (t, 1H), 3.686-3.738 (m, 6H), 3.528-3.3.581 (m, 2H), 3.554-3.577 (t, 6H), 1.216-1.252 (t, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Preparation of Intermediate 8Intermediate 7 Intermediate 8; [0209] A solution of Intermediate 7 (600 mg, 2.95 mmol) dissolved in concentrated aqueous HCI (4 mL) was stirred at 80 C for 2 h. The reaction mixture was cooled to RT, made alkaline (pH ~10) with saturated aqueous NaHC03 (20 mL) and the resulting solution was extracted with DCM (3 x 50 mL). The combined organic layers were washed with water (50 mL), brine (30 mL), dried over Na2S04, filtered and concentrated in vacuo to obtain crude Intermediate 8 (340 mg) as a colorless oil which was used without additional purification. TLC: 60% EtOAc in hexane: Rf: 0.30. | ||
With hydrogenchloride; In water; for 2.0h;Reflux; | Synthesis of compound 62.3. A solution of compound 62.2 (0.650g, 0.37mmol) in cone. HC1 (lOmL) was refluxed for 2h. After completion of the reaction, reaction mixture was allowed to cool at room temperature and dichloromethane (50mL) was added to it. Organic layer was separated out, washed with water (50mL) and brine (50mL) dried over sodium sulphate and used as such in the next step considering 100% yield of compound 62.3 (0.413 g, 100%). | |
With hydrogenchloride; In water; at 80℃; for 2.0h; | A solution of Intermediate 7 (600 mg, 2.95 mmol) dissolved in concentrated aqueous HCl (4 mL) was stirred at 80 C. for 2 h. The reaction mixture was cooled to RT, made alkaline (pH10) with saturated aqueous NaHCO3 (20 mL) and the resulting solution was extracted with DCM (3×50 mL). The combined organic layers were washed with water (50 mL), brine (30 mL), dried over Na2SO4, filtered and concentrated in vacuo to obtain crude Intermediate 8 (340 mg) as a colorless oil which was used without additional purification. TLC: 60% EtOAcin hexane: Rf: 0.30. |
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