Structure of 3970-79-4
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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. : | 3970-79-4 |
Formula : | C8H16ClNO |
M.W : | 177.67 |
SMILES Code : | [H]Cl.O1CCCC12CCNCC2 |
MDL No. : | MFCD11042294 |
InChI Key : | LAAJAVVOPJHOHB-UHFFFAOYSA-N |
Pubchem ID : | 21934981 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 51.15 |
TPSA ? Topological Polar Surface Area: Calculated from |
21.26 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.31 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.34 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.22 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.01 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.17 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.77 |
Solubility | 3.04 mg/ml ; 0.0171 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.36 |
Solubility | 7.81 mg/ml ; 0.0439 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.85 |
Solubility | 2.5 mg/ml ; 0.0141 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) |
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 |
-6.45 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) |
2.05 |
* 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 |
---|---|---|
87% | at 90℃; for 18.0h; | A mixture of cis (RS)-alpha-methyl-N-6-phenyl-1-oxaspiro[2.5]oct-6-yl)-3,5-bis(trifluoromethyl)benzeneacetamide (Example 293, 24 mg, 0.051 mmol) and 1-oxa-8-azaspiro[4.5]decane (Description 75, 70 mg) was stirred in the absence of solvent at 90 C. for 18 hours. The mixture was cooled and purified by flash column chromatography on silica gel, eluting with CH2Cl2/MeOH/NH3(Aq.) (95:5:0.5), to give the title compound (27 mg, 87%). 1H NMR (400 MHz, CDCl3) delta 7.76 (1H, s), 7.64 (2H, s), 7.35-7.20 (5H, m), 5.61 (1H, br s), 3.80 (2H, t, J 7 Hz), 3.56 (1H, q, J 7 Hz), 2.75-2.62 (2H, m), 2.58-2.45 (2H, m), 2.36 (1H, t, J 6 Hz), 2.30 (2H, s), 2.17 (2H, t, J 6 Hz), 1.89 (2H, quin, J 7 Hz), 1.75-1.5 (7H, m), 1.42 (3H, d, J 7 Hz), and 1.50-1.30 (2H, m). m/z (ES+) 613 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With hydrogenchloride; In methanol; at 20℃; for 3.0h; | Methanolic hydrogen chloride (3M, 20 mL) was added over 10 minutes to a stirred, cooled (0 C.) solution of 1,1-dimethylethyl 1-oxa-8-azaspiro[4,5]decane-8-carboxylate (Description 74, 3.18 g, 13.2 mmol) in methanol (10 mL) and the mixture was stirred at room temperature for 3 hours. The solvent was evaporated under reduced pressure to give the title compound (2.29 g, 98%). m/z (ES+) 142 (M+1). |
98% | With hydrogenchloride; In methanol; at 0 - 20℃; for 3.0h; | Methanolic hydrogen chloride (3M, 20ML) was added over 10 minutes to a stirred, cooled (0C) solution of 1, 1-dimethylethyl l-oxa-8-azaspiro [4. 5] DECANE-8-CARBOXYLATE (from step (iv) above, 3. 18G, 13. 2MMOL) in methanol (10ML) and the mixture was stirred at room temperature for 3 hours. The solvent was evaporated under reduced pressure to give the title compound (2. 29g, 98%). 1H NMR (400 MHz, CDC13) : 8 3. 85 (2H, t, J 7Hz), 3.27-3. 15 (4H, m), 1.98 (2H, QUIN. , J7HZ), 1. 86-1. 75 (6H, M); M/Z (ES+) 142 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With triethylamine; In tetrahydrofuran; at 20℃; for 96.0h; | A suspension of the <strong>[3970-79-4]1-oxa-8-azaspiro[4.5]decane hydrochloride</strong> (0.264 g, 1.49 mmol; prepared according to the procedure by WO 0187838, 2001), triethylamine (0.21 mL, 1.5 mmol) and THF (3 mL) was stirred for 30 minutes at room temperature. The mixture was treated with Intermediate 1B (0.18 g, 0.50 mmol) and stirred at room temperature for 4 days and concentrated. The resulting residue was purified by flash chromatography eluding with 0%-20%-50% ethyl acetate/hexane to provide the desired product as a yellow oil (0.139 g, 65% yield). 1H NMR (300 MHz, CDCl3) delta: 7.46-7.43 (1H, m), 7.35-7.27 (2H, m), 5.12 (2H, s), 4.28 (2H, q, J=7.2 Hz), 3.82 (2H, t, J=6.8 Hz), 3.47 (3H, s), 3.31-3.23 (2H, m), 3.18-3.10 (2H, m), 1.97-1.87 (2H, m), 1.74-1.69 (4H, m), 1.55 (2H, br s), 1.26 (3H, t, J=7.1 Hz). LCMS (M+H) calcd for C23H30N3O5: 428.21; found: 428.32. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47% | With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 80℃; for 18.0h; | To a solution l-oxa-8-azaspiro[4.5]decane, HC1 (150 mg, 0.84 mmol) and DIEA (0.44 mL, 2.53 mmol) in anhydrous CH3CN (10 mL) was added isopropyl 2-(5- bromo-4-chloro-2,6-dimethylpyridin-3-yl)-2-oxoacetate (282 mg, 0.84 mmol) at rt. The resulting mixture was placed in a pre-heated oil bath (80 C) and stirred for 18 h; cooled, and concentrated. The crude product was charged (DCM) to a 40 g ISCO silica gel cartridge and gradient elution (5 - 35% EtOAc/hexanes) using an Isolera chromatography station to give isopropyl 2-(5-bromo-2,6-dimethyl-4-(l-oxa-8-azaspiro[4.5]decan-8- yl)pyridin-3-yl)-2-oxoacetate 176 mg (47%). 1H MR (500 MHz, CDC13) delta 5.09-5.04 (m, 1H), 3.73 (t, J=7.0 Hz, 2H), 3.36-3.35 (m, 4H), 2.61 (s, 3H), 2.30 (s, 3H), 1.89-1.84 (m, 2H), 1.66 (t, J=8.1 Hz, 2H), 1.56-1.51 (m, 4H), 1.30 (d, J=5.9 Hz, 6H). UPLC (M+H) = 441.2. |
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