Structure of 149554-03-0
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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. : | 149554-03-0 |
Formula : | C11H19NO3 |
M.W : | 213.27 |
SMILES Code : | O=C(OC(C)(C)C)CN1CCC(CC1)=O |
MDL No. : | MFCD07371646 |
InChI Key : | SBVOSDPEDKERMR-UHFFFAOYSA-N |
Pubchem ID : | 53407149 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 15 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.82 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 61.21 |
TPSA ? Topological Polar Surface Area: Calculated from |
46.61 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.5 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.62 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.61 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.64 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.52 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.18 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.29 |
Solubility | 11.0 mg/ml ; 0.0514 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.17 |
Solubility | 14.3 mg/ml ; 0.0671 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.8 |
Solubility | 3.34 mg/ml ; 0.0157 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 |
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) |
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 |
-7.16 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 |
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) |
1.76 |
* 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 potassium hydroxide; In methanol; for 192.0h;Heating / reflux; | A mixture of 45 (2.1 g, 10 mmol), BOC-piperidone (3.4 g, 17 [MMOL)] and KOH (0.28 g, 5 [MMOL)] in CH30H (150 ml) was [REFLUXED] for eight days. The reaction mixture was then concentrated in vacuo, partitioned between water (50 [ML)] and [CH2CI2] (100 [ML),] and acidified with [ACOH.] The organic layer was isolated and concentrated to provide crude 46. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Referential Example 2 Methyl 1-(tert-butoxycarbonylmethyl)-4-oxo-3-piperidinepropionate Starting compound: <strong>[149554-03-0]Tert-butyl 4-oxo-1-piperidineacetate</strong> Mass spectrum (m/z): FAB (Pos) 300(M+ +1) NMR spectrum (CDCl3, TMS internal standard): delta: 1.48 (9H, s), 1.50-1.59 (1H, m), 2.05-2.15 (1H, m), 2.30-2.46 (4H, m), 2.60-2.70 (3H, m), 3.13-3.17 (2H, m), 3.25 (2H, d), 3.66 (3H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With acetic acid; triethylamine; In methanol; dichloromethane; at 40℃; for 3.0h; | To a mixture of Example 87D (0.200 g, 0.505 mmol) and triethylamine (0.155 mL, 1.1 10 mmol), acetic acid (0.144 mL, 2.52 mmol) in dichloromethane (3 mL) and methanol (3 mL) was added tert-butyl 2-(4-oxopiperidin- 1 -yl)acetate (0.215 g, 1.009 mmol) and MP-cyanoborohydride (Biotage, 81 1 mg, 2.019 mmol). The reaction mixture was heated at 40C for 3 hours. The solid material was filtered and rinsed with dichloromethane and methanol. The filtrate was concentrated. The residue was partitioned in ethyl acetate and saturated aqueous sodium bicarbonate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated until most solvent was evaporated. The precipitates were filtered, washed with cold ethyl acetate, and vacuum oven-dried to provide the title compound. MS (ESI+) m/z 521.1 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69.5% | Example A13e a) Preparation of Int. 229 3-Nitro-aniline (5.0 g; 36.2 mmol) was dissolved in DCE (75 ml). Tert-butyl 4- oxopiperidine-1 -acetate (15.4 g; 72.4 mmol) and acetic acid (4.3 g; 72.4 mmol) were added. The mixture was stirred at r.t. for 1 h, then sodiumacetoxyboro hydride (15.3 g; 72.4 mmol) was added in portions. The mixture was stirred at r.t. overnight. The mixture was washed with water, brine, dried, and concentrated to give 3.0 g of Int. 229 (69.5 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
[000627] A solution of Example 1.2.7 (0.055 g,), fert-butyl 2-(4-oxopiperidin-l-yl)acetate (0.014 g) and sodium triacetoxyborohydride (0.019 g) was stirred in dichloromethane (0.5 mL) at room temperature. After stirring for 2 hours, trifluoroacetic acid (0.5 mL) was added to the reaction, and stirring was continued overnight. The reaction was concentrated, dissolved in N,N- dimethylformamide (1.5 mL) and water (0.5 mL) and purified by reverse phase HPLC using a Gilson system, eluting with 10-80% acetonitrile in water containing 0.1% v/v trifluoroacetic acid. The desired fractions were combined and freeze-dried to provide the title compound. NMR (501 MHz, dimethyl sulfoxide-^) delta ppm 12.85 (s, 1H), 8.80 (s, 2H), 8.03 (d, 1H), 7.80 (d, 1H), 7.62 (d, 1H), 7.55-7.41 (m, 3H), 7.36 (q, 2H), 7.29 (s, 1H), 6.96 (d, 1H), 4.96 (s, 2H), 4.07 (s, 2H), 3.89 (t, 2H), 3.83 (s, 2H), 3.66-3.55 (m, 4H), 3.30 (s, 1H), 3.08 (s, 4H), 3.02 (t, 2H), 2.22 (d, 2H), 2.10 (s, 3H), 1.97-1.78 (m, 2H), 1.44 (s, 2H), 1.31 (q, 4H), 1.20-0.96 (m, 6H), 0.87 (s, 6H). MS (ESI) m/e 887.3 (M+H)+. | ||
A solution of Example 1.2.7 (0.055 g,), <strong>[149554-03-0]tert-butyl 2-(4-oxopiperidin-1-yl)acetate</strong> (0.014 g) and sodium triacetoxyborohydride (0.019 g) was stirred in dichloromethane (0.5 mL) at room temperature. After stirring for 2 hours, trifluoroacetic acid (0.5 mL) was added to the reaction, and stirring was continued overnight. The reaction was concentrated, dissolved in N,N- dimethylformamide (1.5 mL) and water (0.5 mL) and purified by reverse phase HPLC using a Gilson system, eluting with 10-80% acetonitrile in water containing 0.1% v/v trifluoroacetic acid. The desired fractions were combined and freeze-dried to provide the title compound. 1H NMR (501 MHz, dimethyl sulfoxide-d6) delta ppm 12.85 (s, 1H), 8.80 (s, 2H), 8.03 (d, 1H), 7.80 (d, 1H), 7.62 (d, 1H), 7.55-7.41 (m, 3H), 7.36 (q, 2H), 7.29 (s, 1H), 6.96 (d, 1H), 4.96 (s, 2H), 4.07 (s, 2H), 3.89 (t, 2H), 3.83 (s, 2H), 3.66-3.55 (m, 4H), 3.30 (s, 1H), 3.08 (s, 4H), 3.02 (t, 2H), 2.22 (d, 2H), 2.10 (s, 3H), 1.97-1.78 (m, 2H), 1.44 (s, 2H), 1.31 (q, 4H), 1.20-0.96 (m, 6H), 0.87 (s, 6H). MS (ESI) m/e 887.3 (M+H)+. | ||
A solution of Example 1.2. 7 (0.055 g,), tert-butyl 2-( 4-oxopiperidin-1-yl)acetate (0.014 g)and sodium triacetoxyborohydride (0.019 g) was stirred in dichloromethane (0.5 mL) at roomtemperature. After stirring for 2 hours, trifluoroacetic acid (0.5 mL) was added to the reaction, andstirring was continued overnight. The reaction was concentrated, dissolved in N,N-25 dimethylformamide (1.5 mL) and water (0.5 mL) and purified by reverse phase HPLC using a Gilsonsystem, eluting with 10-80% acetonitrile in water containing 0.1% v/v trifluoroacetic acid. Thedesired fractions were combined and freeze-dried to provide the title compound. 1H NMR (501 MHz,dimethyl sulfoxide-d6) 8 ppm 12.85 (s, 1H), 8.80 (s, 2H), 8.03 (d, 1H), 7.80 (d, 1H), 7.62 (d, 1H),7.55-7.41 (m, 3H), 7.36 (q, 2H), 7.29 (s, 1H), 6.96 (d, 1H), 4.96 (s, 2H), 4.07 (s, 2H), 3.89 (t, 2H),30 3.83 (s, 2H), 3.66-3.55 (m, 4H), 3.30 (s, 1H), 3.08 (s, 4H), 3.02 (t, 2H), 2.22 (d, 2H), 2.10 (s, 3H),1.97-1.78 (m, 2H), 1.44 (s, 2H), 1.31 (q, 4H), 1.20-0.96 (m, 6H), 0.87 (s, 6H). MS (ESI) m/e 887.3(M+Ht. |
A solution of Example 1.2.7 (0.055 g,), <strong>[149554-03-0]tert-butyl 2-(4-oxopiperidin-1-yl)acetate</strong> (0.014 g) and sodium triacetoxyborohydride (0.019 g) was stirred in dichloromethane (0.5 mL) at room temperature. After stirring for 2 hours, trifluoroacetic acid (0.5 mL) was added to the reaction, and stirring was continued overnight. The reaction was concentrated, dissolved in N,N-dimethylformamide (1.5 mL) and water (0.5 mL) and purified by reverse phase HPLC using a Gilson system, eluting with 10-80% acetonitrile in water containing 0.1% v/v trifluoroacetic acid. The desired fractions were combined and freeze-dried to provide the title compound. 1H NMR (501 MHz, dimethyl sulfoxide-d6) delta ppm 12.85 (s, 1H), 8.80 (s, 2H), 8.03 (d, 1H), 7.80 (d, 1H), 7.62 (d, 1H), 7.55-7.41 (m, 3H), 7.36 (q, 2H), 7.29 (s, 1H), 6.96 (d, 1H), 4.96 (s, 2H), 4.07 (s, 2H), 3.89 (t, 2H), 3.83 (s, 2H), 3.66-3.55 (m, 4H), 3.30 (s, 1H), 3.08 (s, 4H), 3.02 (t, 2H), 2.22 (d, 2H), 2.10 (s, 3H), 1.97-1.78 (m, 2H), 1.44 (s, 2H), 1.31 (q, 4H), 1.20-0.96 (m, 6H), 0.87 (s, 6H). MS (ESI) m/e 887.3 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In tetrahydrofuran; for 4.0h; | To the solution of piperidin-4-one (10 mmol) inTHF (20 mL) was added tert-Butyl bromoacetate (11 mmol), and the mixture was stirredfor 4 h. The mixture was poured to H20 and extracted with EtOAc (3X). The combined organic was washed with brine, dried with Na2504. The solvent was removed under vacuum to afford the crude amineketone, which was used for next step without purification. To the suspension of crude amineketone (1 mmol) in CH2C12 was addedm-CPBA (2 mmol) at 0 C. The mixture was stirred for 8 h at room temp. The aqueous Na2 S203 was added and the mixture was extracted with CH2C12, washed with brine and dried with Na2504. The solvent was removed under vacuum, and the residual was purified with flash column (MeOH : CH2C12 1:4) to give desired lactone (40% for 3 steps). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 3-chloro-benzenecarboperoxoic acid; In dichloromethane; at 0 - 20℃; for 8.0h; | To the solution of piperidin-4-one (10 mmol) inTHF (20 mL) was added tert-Butyl bromoacetate (11 mmol), and the mixture was stirredfor 4 h. The mixture was poured to H20 and extracted with EtOAc (3X). The combined organic was washed with brine, dried with Na2504. The solvent was removed under vacuum to afford the crude amineketone, which was used for next step without purification. To the suspension of crude amineketone (1 mmol) in CH2C12 was addedm-CPBA (2 mmol) at 0 C. The mixture was stirred for 8 h at room temp. The aqueous Na2 S203 was added and the mixture was extracted with CH2C12, washed with brine and dried with Na2504. The solvent was removed under vacuum, and the residual was purified with flash column (MeOH : CH2C12 1:4) to give desired lactone (40% for 3 steps).?H NMR (400 MHz, CDC13) 1.47 (s, 9H), 2.52 (t, J = 7.9 Hz, 2H), 2.94 t, J =7.9 Hz, 2H), 3.26 (s, 2H), 3.80 (m, 2H), 4.25 (m, 2H). |