Structure of 164456-75-1
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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. : | 164456-75-1 |
Formula : | C12H21NO4 |
M.W : | 243.30 |
SMILES Code : | O=C(N1[C@@H](C(OC)=O)CCCC1)OC(C)(C)C |
MDL No. : | MFCD09038772 |
InChI Key : | PVMJFJDVCVNWQN-SECBINFHSA-N |
Pubchem ID : | 45072456 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 17 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.83 |
Num. rotatable bonds | 5 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 67.49 |
TPSA ? Topological Polar Surface Area: Calculated from |
55.84 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.03 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.91 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.57 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.31 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.03 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.77 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.22 |
Solubility | 1.46 mg/ml ; 0.006 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.71 |
Solubility | 0.479 mg/ml ; 0.00197 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.36 |
Solubility | 10.7 mg/ml ; 0.044 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 |
-6.43 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) |
2.95 |
* 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 |
---|---|---|
64% | Example 2.1; (R)-2-Formyl-piperidine-1-carboxylic acid tert-butyl ester; To the title compound of Example 1.1 (5.4 g, 22.1 mmol) in toluene (50 mL) at -78 C. was added 1.5 M DIBAL in toluene (33.8 mL, 50.7 mmol) drop-wise over 40 minutes. Methanol (120 mL) was then added drop-wise at -78 C. over 10 minutes. The reaction mixture was moved to an ice-bath where 10% wt citric acid (500 mL) was added and then the mixture was stirred for an additional 1 hour. After the resulting mixture was extracted with ethyl acetate (2 times), the organic layer was washed with water and brine, dried over anhydrous Na2SO4, filtered and concentrated to give the title product as a colorless oil (3.0 g, 64%).1H NMR (300 MHz, CDCl3): delta 9.61 (s, 1H), 4.60 (m, 1H), 4.96 (m, 1H), 2.91 (m, 1H), 2.19 (m, 1H), 1.49 (m, 14H) | |
64% | Example 2.1(R)-2-Formyl-piperidine-1-carboxylic acid tert-butyl ester To the title compound of Example 1.1 (5.4 g, 22.1 mmol) in toluene (50 mL) at -78 C. was added 1.5 M DIBAL in toluene (33.8 mL, 50.7 mmol) drop-wise over 40 minutes. Methanol (120 mL) was then added drop-wise at -78 C. over 10 minutes. The reaction mixture was moved to an ice-bath where 10% wt citric acid (500 mL) was added and then mixture was stirred for an additional 1 hour. After the resulting mixture was extracted with ethyl acetate (2 times), the organic layer washed with water and brine, dried over anhydrous Na2SO4, filtered and concentrated to give the title product as a colorless oil (3.0 g, 64%).1H NMR (300 MHz, CDCl3): delta (ppm) 9.61 (s, 1H), 4.60 (m, 1H), 4.96 (m, 1H), 2.91 (m, 1H), 2.19 (m, 1H), 1.49 (m, 14H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; | Example 1.1; (R)-Piperidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester; To (R)-Piperidine-1,2-dicarboxylic acid 1-tert-butyl ester (5.1 g, 22.2 mmol) in DMF (60 mL) were added K2CO3 (12.3 g, 88.8 mmol) and Mel (1.7 mL, 26.6 mmol). After stirring at room temperature overnight, the reaction mixture was diluted with ethyl acetate. The organic layer was washed with water (6 times) and brine, dried over anhydrous Na2SO4, filtered and concentrated to give the title product (5.4 g, 99%).1H NMR (300 MHz, CDCl3): delta 4.82 (m, 1H), 3.99 (m, 1H), 3.75 (s, 3H), 2.95 (m, 1H), 2.21 (m, 1H), 2.45 (m, 14H). |
99% | With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; | Example 1.1(R)-Piperidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester To (R)-Piperidine-1,2-dicarboxylic acid 1-tert-butyl ester (5.1 g, 22.2 mmol) in DMF (60 mL) were added K2CO3 (12.3 g, 88.8 mmol) and MeI (1.7 mL, 26.6 mmol). After stirring at room temperature overnight, the reaction mixture was diluted with ethyl acetate. The organic layer washed with water (6 times) and brine, dried over anhydrous Na2SO4, filtered and concentrated to give the title product (5.4 g, 99%).1H NMR (300 MHz, CDCl3): delta (ppm) 4.82 (m, 1H), 3.99 (m, 1H), 3.75 (s, 3H), 2.95 (m, 1H), 2.21 (m, 1H), 2.45 (m, 14H) |
With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 40℃; for 4.5h; | [0191] To a solution of N-BOC-pipecolinic acid (166.5 g, 726 mmoles) in 500 mL dimethylformamide (DMF) was added MeI (123.7 g, 871 mmoles) and K2CO3 (100.4 g, 726 moles). The reaction mixture slowly exothermed to 40 C. after 0.5 h during a 4 h age period at ambient temperature. Added MTBE (830 mL) and then washed with H2O (2×830 mL) and 20% brine (300 mL). The organic layer was dried over Na2SO4 and concentrated to an oil (3). |
With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 20 - 40℃; for 4.5h; | PREPARATIVE EXAMPLE 3; To a solution of N-BOC-pipecolinic acid (166.5 g, 726 mmoles) in 500 mL dimethylformamide (DMF) was added MeI (123.7 g, 871 mmoles) and K2CO3 (100.4 g, 726 moles). The reaction mixture slowly exothermed to 40 C. after 0.5 h during a 4 h age period at ambient temperature. Added MTBE (830 mL) and then washed with H2O (2×830 mL) and 20% brine (300 mL). The organic layer was dried over Na2SO4 and concentrated to an oil (3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium bromate;ruthenium trichloride; In water; acetonitrile; at 20℃; for 14h; | [0193] To a solution of butoxycarbonyl (Boc)-Me ester (152.6 g, 627 mmol) in MeCN (305 mL) was added RuCl3 (2.6 g, 12.5 mmol). A solution of NaBrO3 (142.0 g, 941 mmol) in H2O (760 mL) was added over 2 h. The solution was aged 12 h at ambient temperature. Added EtOAc (760 mL) and cut the aqueous layer. The dark organic layer was washed with 10% Na2SO3 (305 mL) while the organic layer turned clear and the aqueous layer turned cloudy grey. The organic layer was washed with saturated brine (150 mL) and then dried over Na2SO4 to give oil (4). | |
With sodium bromate;rubidium chloride; In water; acetonitrile; at 20℃; for 14h; | PREPARATIVE EXAMPLE 4; To a solution of butoxycarbonyl (Boc)-Me ester (152.6 g, 627 mmol) in MeCN (305 mL) was added RuCl3 (2.6 g, 12.5 mmol). A solution of NaBrO3 (142.0 g, 941 mmol) in H2O (760 mL) was added over 2 h. The solution was aged 12 h at ambient temperature. Added EtOAc (760 mL) and cut the aqueous layer. The dark organic layer was washed with 10% Na2SO3 (305 mL) while the organic layer turned clear and the aqueous layer turned cloudy grey. The organic layer was washed with saturated brine (150 mL) and then dried over Na2SO4 to give oil (4). |
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