Structure of 4497-04-5
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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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Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 4497-04-5 |
Formula : | C7H13NO3 |
M.W : | 159.18 |
SMILES Code : | O=C(O)CCN1CCOCC1 |
MDL No. : | MFCD02089311 |
InChI Key : | YUYHRSGXZZVNMS-UHFFFAOYSA-N |
Pubchem ID : | 410813 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.86 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 43.32 |
TPSA ? Topological Polar Surface Area: Calculated from |
49.77 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.58 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-2.89 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-0.59 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.5 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.35 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.41 |
Log S (ESOL):? ESOL: Topological method implemented from |
1.19 |
Solubility | 2480.0 mg/ml ; 15.6 mol/l |
Class? Solubility class: Log S scale |
Highly soluble |
Log S (Ali)? Ali: Topological method implemented from |
2.4 |
Solubility | 40200.0 mg/ml ; 253.0 mol/l |
Class? Solubility class: Log S scale |
Highly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.24 |
Solubility | 92.2 mg/ml ; 0.579 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 |
-9.32 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 |
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<1.0 |
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 |
---|---|---|
89% | With potassium hydroxide; In ethanol; | The starting material was prepared as follows: Potassium hydroxide (485 mg, 8.6mmol) was added to a solution of methyl 3-morpholinopropionate (1 g, 5.7 mmol) in ethanol (20 ml) and the mixture stirred for 2 hours at 80° C. The solution was allowed to cool and adjusted to pH1 with 6M hydrochloric acid. Insoluble material was removed by filtration and the volatiles removed from the filtrate by evaporation. The resulting oil was triturated with ether, the solid product collected by filtration, washed with methylene chloride and dried under vacuum to give 3-morpholinopropionic acid (993 mg, 89percent) as a white solid. 1H NMR Spectrum: (DMSOd6; CF3COOD) 2.83(t, 2H); 3.13(t, 2H); 3.36(t, 2H); 3.46(d, 2H); 3.73(t, 2H); 3.97(d, 2H) MS-ESI: 159 [MH]+ |
Example 17 Preparation of [3-(2-morpholin-4-yl-ethyl)-imidazo[1,5-a]pyridin-1-yl]-naphthalen-1-yl-methanone To a solution of methyl 4-morpholinepropionate (5.0 g, 28.9 mmol) in MeOH (25 mL) was added 2N NaOH (17.3 mL, 34.6 mmol). The mixture was stirred for 1 h then concentrated in vacuo. The residue was suspended in dichloromethane (125 mL) and DMF (30 muL) was added followed by oxalylchloride (10 mL, 115.6 mmol). The mixture was allowed to stir for 2 h. then concentrated in vacuo. The resulting solid was added portion-wise to a solution of 2-(aminomethyl)pyridine (2.88 mL, 28.2 mmol) and triethylamine (9.0 mL, 64.86 mmol) in dichloromethane (200 mL). The mixture was stirred at ambient temperature for 1 h. then washed with water (300 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated to yield 3-morpholin-4-yl-N-pyridin-2-ylmethyl-propionamide (5.56 g, 77percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
B. 3-(4-Morpholinyl)propanoic Acid A solution of the resultant compound of Example 202A (8.35 g, 48.3 mmol) in 60 ml of dioxane was treated with 40 ml of water and 19.3 ml (58 mmol) of 3N aqueous NaOH. After being stirred for 4 h, the solution was treated with 58 ml (58 mmol) of 1N aqueous HCl and concentrated in vacuo to provide the crude desired compound. | ||
beta-Morpholino-propionic acid (used for preparing compound No. 32) NMR (60 MHz, delta values in CD3 OD): 2.45 (2H, t, J=6 Hz, --COCH2 --) STR31 3.83 (4H, m, --CH2 OCH2 --) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | Example 7; 4-[5-amino- l-(2,6-difluoro-benzoyl)- lH-[ 1 ,2,4]triazol-3- ylamino]-N-(3-morpholin-4-yl-propionyl)-benzenesulfonamide(Cpd 7); 7a; Using the mixed anhydride formation procedure, 1.9 g (100 percent) of Compound7a was generated from morpholinylpropionic acid (1.25 g) and pivaloyl chloride (1.05 g). 1H NMR (300 MHz, CDCl3) delta 3.68 (m, 4 H), 2.75 (t, 2 H), 2.65 (t, 2 H), 2.45 (m, 4 H), 1.21 (s, 9 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In chloroform; at 20℃; for 20.16h; | [[0158]] B. Homocamptothecin-20-O ester of N-morpholine propionic acid The target molecule is synthesized using the above procedure for this example. The flask is charged with homocamptothecin [(HCPT)] (20 mg,. 05 mmol) and then 7 mL of dry chloroform. The solution is allowed to stir for 10 minutes at ambient temperature. [1- (3-] [DIMETHYLAMINO-PROPYL)-3-ETHYL-CARBODIIMIDE] hydrochloride (EDCI) (61 mg, 0.31 mmol), 4- (dimethylamino) pyridine (DMAP) (12 mg, . 12 mmol) and N-morpholine propionic acid (23 mg, . 15 mmol) is added. The reaction is allowed to stir for 20 hours at ambient temperature and worked up according to the procedure. |