Structure of 676560-01-3
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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. : | 676560-01-3 |
Formula : | C10H12FNO2 |
M.W : | 197.21 |
SMILES Code : | O=C(OC(C)(C)C)C1=CN=C(F)C=C1 |
MDL No. : | MFCD26743533 |
InChI Key : | RZWMKWGTXCIWLV-UHFFFAOYSA-N |
Pubchem ID : | 66756622 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.4 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 49.93 |
TPSA ? Topological Polar Surface Area: Calculated from |
39.19 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.4 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.12 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.6 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.7 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.32 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.23 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.52 |
Solubility | 0.599 mg/ml ; 0.00304 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.57 |
Solubility | 0.526 mg/ml ; 0.00267 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.21 |
Solubility | 0.122 mg/ml ; 0.000619 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) |
Yes |
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 |
-6.0 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 |
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) |
2.06 |
* 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 |
---|---|---|
In 1,4-dioxane; hexane; | Example 40B 4-Amino-4-methyl-3, 4, 5, 6-tetrahydro-2H-(1,2') bipyridinyl-5'-carboxylic acid tert-butyl ester To a stirred solution of (4-methyl-piperidin-4-yl)-carbamic acid benzyl ester (0.31 g, 1.28 mmol, Example 30B) in dioxane (5.0 mL) at room temperature was added <strong>[676560-01-3]6-fluoro-nicotinic acid tert-butyl ester</strong> (0.21 g, 1.07 mmol). The reaction mixture was stirred at 80 C. for 18 hours, concentrated under reduced pressure and purified by flash chromatography with 10% to 30% ethyl acetate in hexane to provide 4-benzyloxycarbonylamino-4-methyl-3,4,5,6-tetrahydro-2H-(1,2')bipyridinyl-5'-carboxylic acid tert-butyl ester. MS (CI) m/z 426 (M+1)+; 1H NMR (300 MHz, CDCl3) delta ppm 8.74(d, 1H), 7.97 (dd, 1H), 7.35 (m, 5H), 7.26 (s, 1H), 5.07 (s, 2H), 4.68 (s, 1H), 3.97 (m, 2H), 3.37 (m, 2H), 2.08 (m, 2H), 1.66 (m, 2H), 1.56 (s, 9H), 1.42 (s, 3H). | |
In 1,4-dioxane; hexane; | Example 40B 4-Amino-4-methyl-3,4,5,6-tetrahydro-2H-(1,2')bipyridinyl-5'-carboxylic acid tert-butyl ester To a stirred solution of (4-methyl-piperidin-4-yl)-carbamic acid benzyl ester (0.31 g, 1.28 mmol, Example 30B) in dioxane (5.0 mL) at room temperature was added <strong>[676560-01-3]6-fluoro-nicotinic acid tert-butyl ester</strong> (0.21 g, 1.07 mmol). The reaction mixture was stirred at 80 C. for 18 hours, concentrated under reduced pressure and purified by flash chromatography with 10% to 30% ethyl acetate in hexane to provide 4-benzyloxycarbonylamino-4methyl-3,4,5,6-tetrahydro-2H-(1,2')bipyridinyl-5'-carboxylic acid tert-butyl ester. MS (CI) m/z 426 (M+1)+; 1H NMR (300 MHz, CDCl3) delta ppm 8.74(d, 1H), 7.97 (dd, 1H), 7.35 (m, 5H), 7.26 (s, 1H), 5.07 (s, 2H), 4.68 (s, 1H), 3.97 (m, 2H), 3.37 (m, 2H), 2.08 (m, 2H), 1.66 (m, 2H), 1.56 (s, 9H), 1.42 (s, 3H). | |
In 1,4-dioxane; at 20 - 80℃; for 18.0h; | To a stirred solution of (4-methyl-piperidin-4-yl) -carbamic acid benzyl ester (0.31 g, 1.28 mmol, Example 30B) in dioxane (5.0 mL) at room temperature was added 6-fluoro- nicotinic acid tert-butyl ester (0.21 g, 1.07 [MMOL).] The reaction mixture was stirred at 80 [C] for 18 hours, concentrated under reduced pressure and purified by flash chromatography with 10% to 30% ethyl acetate in hexane to provide 4-benzyloxycarbonylamino-4-methyl-3,4, 5,6- [TETRAHYDRO-2H- (1, 2') BIPYRIDINYL-5'-CARBOXYLIC] acid tert-butyl ester. MS (CI) m/z 426 (M+1) [+] ; [JH] NMR (300 MHz, CDC13) 8 ppm 8.74 (d, [1H),] 7.97 (dd, 1H), 7.35 [(M,] [5H),] 7.26 (s, [1H),] 5.07 (s, 2H), 4.68 (s, [1H),] 3.97 (m, 2H), 3.37 [(M,] 2H), 2.08 [(M,] 2H), 1.66 (m, 2H), 1.56 (s, 9H), 1.42 (s, 3H). To a stirred solution [OF 4-BENZYLOXYCARBONYLAMINO-4-METHYL-3, 4, 5, 6-TETRAHYDRO-2H-] (1, 2') [BIPYRIDINYL-5'-CARBOXYLIC] acid tert-butyl ester (0.29 g, 0.68 mmol) in isopropanol, methanol and ethyl acetate (1: 1: 1,5. 0 mL) at room temperature was added ammonium formate (0.25 g, 1.07 mmol) and 10% Pd/C (25 mg) under nitrogen. The reaction mixture was stirred at 80 [C] for 30 minutes, cooled, filtered through Celite, and concentrated under reduced pressure to provide the titled compound. MS (CI) m/z 292 (M+1) [+] [;'H] NMR (300 MHz, methanol-d4) [8] ppm 8.61 (d, [1H),] 7.95 (d, d [1H),] 6.79 (d, [1H),] 4.80 (s, 2H), 3.85-3. 79 [(M,] 2H), 3.66-3. 60 [(M,] 2H), 1.67-1. 59 (m, 4H), 1.58 (s, 9H), 1.23 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N,N-dimethylformamide di-tert-butyl acetal; for 3.0h;Heating / reflux; | To a stirred and refluxed solution of 6-fluoro-nicotinic acid (0.092 g, 6.52 mmol) in benzene and 2-methyl-propan-2-ol (2: 1,15 : 7 mL) was added dropwise N, N- [DIMETHYLFORMAMIDE] di-tert-butyl acetal (8.2 mL, 29.6 mmol). The reaction mixture was refluxed for 3 hours, cooled to room temperature and partitioned between aqueous [NAHC03] and dichloromethane. The organic layer was washed with water and brine, dried [(MGS04),] filtered, concentrated under reduced pressure and purified by flash chromatography with 15% to 30% ethyl acetate in hexane to provide the titled compound. MS (CI) m/z 197 (M+1) [+] [; IH] NMR (300 MHz, CDC13) [5] ppm 8.82 (d, 1H), 8.38 (m, 1H), 6.98 (d, [1H),] 1.64 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In hexane; benzene; | Example 40A 6-Fluoro-nicotinic acid tert-butyl ester To a stirred and refluxed solution of 6-fluoro-nicotinic acid (0.092 g, 6.52 mmol) in benzene and 2-methyl-propan-2-ol (2:1, 15:7 mL) was added dropwise N,N-dimethylformamide di-tert-butyl acetal (8.2 mL, 29.6 mmol). The reaction mixture was refluxed for 3 hours, cooled to room temperature and partitioned between aqueous NaHCO3 and dichloromethane. The organic layer was washed with water and brine, dried (MgSO4), filtered, concentrated under reduced pressure and purified by flash chromatography with 15% to 30% ethyl acetate in hexane to provide the titled compound. MS (CI) m/z 197 (M+1)+; 1H NMR (300 MHz, CDCl3) delta ppm 8.82(d, 1H), 8.38(m, 1H), 6.98(d, 1H), 1.64 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In N-methyl-acetamide; | Example 190A 6-(4-amino-4-methyl-cyclohexyloxy)-N,N-dimethyl-nicotinamide To a mixture of sodium hydride (240 mg, 6.0 mmol) in dimethylformamide (10 mL) at 0 C. was added Example 45F (258 mg, 2.0 mmol). The resulting mixture was stirred at 0 C. for 30 minutes, then Example 40A (473 mg, 2.4 mmol) was added. It was heated to 60 C. for 2 hours and stirred for 12 hours at room temperature. The reaction mixture was diluted with ethyl acetate and washed with water (3 times) and brine. The organic layer was dried (sodium sulfate), filtered, and concentrated under reduced pressure to provide the titled compound. MS (DCI) m/z 278 (M+H)+. | |
In N-methyl-acetamide; | Example 190A 6-(4-amino-4-methyl-cyclohexyloxy)-N,N-dimethyl-nicotinamide To a mixture of sodium hydride (240 mg, 6.0 mmol) in dimethylformamide (10 mL) at. 0 C. was added Example 45F (258 mg, 2.0 mmol). The resulting mixture was stirred at 0 C. for 30 minutes, then Example 40A (473 mg, 2.4 mmol) was added. It was heated to 60 C. for 2 hours and stirred for 12 hours at room temperature. The reaction mixture was diluted with ethyl acetate and washed with water (3 times) and brine. The organic layer was dried (sodium sulfate), filtered, and concentrated under reduced pressure to provide the titled compound. MS (DCI) m/z 278 (M+H)+. |
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