Structure of 204862-70-4
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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. : | 204862-70-4 |
Formula : | C8H9NO3 |
M.W : | 167.16 |
SMILES Code : | O=CC1=C(OC)C=NC=C1OC |
MDL No. : | MFCD06410671 |
InChI Key : | WJPFKYRAVTUOIZ-UHFFFAOYSA-N |
Pubchem ID : | 2762982 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 42.61 |
TPSA ? Topological Polar Surface Area: Calculated from |
48.42 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.53 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.26 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.91 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.73 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.47 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.69 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.21 |
Solubility | 10.3 mg/ml ; 0.0613 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.84 |
Solubility | 24.3 mg/ml ; 0.145 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.22 |
Solubility | 1.0 mg/ml ; 0.00601 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 |
-7.14 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) |
1.74 |
* 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 |
---|---|---|
Preparation Example 8 Synthesis of 3,5-dimethoxy-4-pyridinecarbaldehyde In a similar manner to that in Preparation Example 7, the title compound was prepared. 1 H-NMR(CDCl3) delta: 4.02(6H, s), 8.17(2H, s), 10.50(1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
29% | With sodium cyanoborohydride; zinc(II) chloride; In methanol; at 20℃; for 24h; | A mixture of [3-(6-morpholin-4-yl-9-piperidin-4-yl-9H-purin-2-yl)phenyl]methanol (30 mg, 0.076 mmol), NaCNBH3 (25 mg, 0.40 mmol), zinc chloride (20 mg, 0.183 mmol) and <strong>[204862-70-4]3,5-dimethoxy-4-pyridinecarbaldehyde</strong> (62 mg, 0.37 mmol) in methanol is stirred for 24 hours at room temperature. The mixture is then filtered, dissolved in DMSO (1 mL) and purified by chromatography by HPLC to give 12 mg (29% yield) of the title product (MS (ESI) m/z 546.6). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With sodium cyanoborohydride; zinc(II) chloride; In methanol; at 20℃; for 24h; | A mixture of [3-(6-morpholin-4-yl-9-piperidin-4-yl-9H-purin-2-yl)phenol (50 mg, 0.131 mmol), NaCNBH3 (25 mg, 0.40 mmol), zinc chloride (20 mg, 0.183 mmol) and <strong>[204862-70-4]3,5-dimethoxy-4-pyridinecarbaldehyde</strong> (44 mg, 0.262 mmol) in methanol is stirred for 24 hours at room temperature. The mixture is then filtered, dissolved in DMSO (1 mL) and purified by chromatography by HPLC to give 41 mg (59% yield) of the title product (MS (ESI) m/z 532.7). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With n-butyllithium; In tetrahydrofuran; at -78 - 0℃; for 0.5h; | [0316] To a solution of <strong>[18677-48-0]3,5-dimethoxypyridine</strong> (3.6 g, 25.90 mmol, 1 eq.) in THF (80 mL) was added BuLi (3Mhexanes, 13.0 mL, 38.85 mmol, 1.5 eq.) at-20 C. The mixture was warmed to 0 C, stirred at 0 C for 30 mm, cooled back down to -78 C, and added DMF (3.8 g, 51.8 mmol,2 eq.). The mixture was gradually warmed to 0 C, quenched with NH4C1(saL) solution, and diluted with EtOAc. The aqueous layer was extracted with EtOAc twice. The combined organic layers were washed with brine, dried over Na2SO4, concentrated, and purified on silica gel using a mixture of EtOAc and hexanes as eluent to give 3 ,5-dimethoxyisonicotinaldehyde (2.7 g, 62%) as a yellow solid. LRMS (M+H+) mz 168.1. |
62% | Step 2 To a solution of <strong>[18677-48-0]3,5-dimethoxypyridine</strong> (3.6 g, 25.90 mmol, 1 eq.) in THF (80 mL) was added BuLi (3M/hexanes, 13.0 mL, 38.85 mmol, 1.5 eq.) at -20 C. The mixture was warmed to 0 C., stirred at 0 C. for 30 min, cooled back down to -78 C., and added DMF (3.8 g, 51.8 mmol, 2 eq.). The mixture was gradually warmed to 0 C., quenched with NH4Cl(sat.) solution, and diluted with EtOAc. The aqueous layer was extracted with EtOAc twice. The combined organic layers were washed with brine, dried over Na2SO4, concentrated, and purified on silica gel using a mixture of EtOAc and hexanes as eluent to give 3,5-dimethoxyisonicotinaldehyde (2.7 g, 62%) as a yellow solid. LRMS (M+H+) m/z 168.1. | |
45% | To a stirred solution of lithium diisopropylamide ("LDA", 1.2 mmol) in THF (4 mL) at -78 0C was added a solution of Intermediate 23 (139 mg, 1.0 mmol) at a rate which kept the temperature below -70 0C. The reaction mixture was stirred for 30 minutes and then DMF (0.12 mL, 1.5 mmol) was added drop wise. Upon completion of addition, the reaction mixture was stirred for Ih and then diluted with EtOAc (10 mL). The resulting mixture was washed with satd NaHCO3 (5 mL), brine (5 mL), dried over Na2SO4 and filtered. The volatiles were removed under reduced pressure to provide a residue. The residue was subjected to chromatography on silica gel eluting with 0 to 70% EtOAc/hexanes to provide Intermediate 24 as a pale yellow solid (75 mg, 45%). 1H NMR (400 MHz, CDCl3) delta ppm 3.95 (s, 6 H), 8.11 (s, 2 H), 10.44 (s, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
17% | With aluminum (III) chloride; In dichloromethane;Reflux; | [0317] To a solution of <strong>[204862-70-4]3,5-dimethoxyisonicotinaldehyde</strong> (2.7 g, 16.16 mmol, 1 eq.) in DCM (100 mL)was added A1C13 (4.31 g, 32.32 mmol, 2.0 eq.) atrt. The mixture was reflux 0/N, cooled to rt, and added into ice (200 g). The aqueous layer was extracted with DCM three times.The combined organic layers were dried over Na2SO4, concentrated, and purified on silica gelusing a mixture of EtOAc and hexanes as eluent to give 3-hydroxy-5-methoxyisonicotinaldehyde(420 mg, 17%) as an off-white solid. 1H NMR (400 MHz, CDCl3) 10.96 (s, 1H), 10.26 (s, 1H),7.96 (s, 1H), 7.80 (s, 1H), 3.84 (s, 3H). LRMS (M+H+) m/z 154.1. |
17% | With aluminum (III) chloride; In dichloromethane;Reflux; | Step 3 ;To a solution of <strong>[204862-70-4]3,5-dimethoxyisonicotinaldehyde</strong> (2.7 g, 16.16 mmol, 1 eq.) in DCM (100 mL) was added AlCl3 (4.31 g, 32.32 mmol, 2.0 eq.) at rt. The mixture was reflux O/N, cooled to rt, and added into ice (200 g). The aqueous layer was extracted with DCM three times. The combined organic layers were dried over Na2SO4, concentrated, and purified on silica gel using a mixture of EtOAc and hexanes as eluent to give 3-hydroxy-5-methoxyisonicotinaldehyde (420 mg, 17%) as an off-white solid. 1H NMR (400 MHz, CDCl3) delta 10.96 (s, 1H), 10.26 (s, 1H), 7.96 (s, 1H), 7.80 (s, 1H), 3.84 (s, 3H). LRMS (M+H+) m/z 154.1. |
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