Structure of 847818-55-7
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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. : | 847818-55-7 |
Formula : | C4H7BN2O2 |
M.W : | 125.92 |
SMILES Code : | CN1N=CC(B(O)O)=C1 |
MDL No. : | MFCD09414709 |
InChI Key : | RYGOBSYXIIUFOR-UHFFFAOYSA-N |
Pubchem ID : | 11263501 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 33.31 |
TPSA ? Topological Polar Surface Area: Calculated from |
58.28 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 |
-0.86 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-1.9 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-1.79 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-2.09 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-1.33 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.42 |
Solubility | 47.4 mg/ml ; 0.377 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
0.12 |
Solubility | 165.0 mg/ml ; 1.31 mol/l |
Class? Solubility class: Log S scale |
Highly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
0.35 |
Solubility | 285.0 mg/ml ; 2.26 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
No |
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 |
-7.68 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 |
2.0 |
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) |
1.81 |
* 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 |
---|---|---|
50% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 100℃; for 2h;Inert atmosphere; | Example 109 Synthesis of N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-2-methyl-5-(1-methyl-1H-pyrazol-4-yl)benzamide To a stirred solution of <strong>[1403257-80-6]5-bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-2-methylbenzamide</strong> (0.2 g, 0.42 mmol) and (1-methyl-1H-pyrazol-4-yl)boronic acid (0.105 g, 0.505 mmol) in dioxane/water mixture (5 mL+1 mL), Na2CO3 (0.16 g, 1.51 mmol) was added and solution purged with argon for 15 min. Pd (PPh3)4 (0.048 g, 0.042 mmol) was then added and the reaction mixture again purged with argon for 10 min. The reaction mixture was heated at 100 C. for 2 h. The reaction mixture was then diluted with water and extracted with 10% MeOH/DCM. The combined extracts were dried over Na2SO4 and the solvent removed under reduced pressure to afford the crude product which was purified by column chromatography to afford the title compound (0.100 g, 50%). LCMS: 478.20 (M+1)+; HPLC: 95.82% ( 254 nm) (Rt; 4.322; Method: Column: YMC ODS-A 150 mm*4.6 mm*5mu; Mobile Phase: A; 0.05% TFA in water/B; 0.05% TFA in acetonitrile; Inj. Vol: 10 muL, Col. Temp.: 30 C.; Flow rate: 1.4 mL/min.; Gradient: 5% B to 95% B in 8 min, Hold for 1.5 min, 9.51-12 min 5% B); 1H NMR (DMSO-d6, 400 MHz) delta 11.45 (s, 1H), 8.12 (s, 1H), 8.10 (t, 1H), 7.81 (s, 1H), 7.33 (s, 1H), 7.13 (s, 1H), 5.86 (s, 1H), 4.27 (d, 2H, J=4.8 Hz), 3.81-3.83 (m, 5H), 3.21-3.26 (m, 2H), 2.98-3.08 (m, 3H), 2.20 (s, 3H), 2.17 (s, 3H), 2.10 (s, 3H), 1.63-1.66 (m, 2H), 1.48-1.52 (m, 2H), 0.86 (t, 3H, J=7.2 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 120℃; for 1.0h;Inert atmosphere; Microwave irradiation; | For 3 min, N2 was bubbled through a mixture of <strong>[33930-63-1]4-bromo-2-methylisoquinolin-1(2H)-one</strong> (54 mg, 0.23 mmol), (1-methylpyrazol-4-yl)boronic acid (31 mg, 0.25 mmol), aqueous 2M Na2CO3 (0.375 mL) and Pd(dppf)Cl2 (8 mg, 0.01 mmol) in 1,4-dioxane (1.5 mL) which was then microwaved at 120° C. for 1 h. Work up in a manner similar to Example 18, step 3, and two successive silica gel chromatographies, eluting with 15-80percent EA in hexane over 6 min and continuing 80percent isocratic EA followed by a second chromatography 15-100percent EA in hexane over 6 min and continuing 100percent isocratic EA gave the title compound (28 mg, 0.12 mmol) as a cream solid in 51percent yield. 1H NMR (400 MHz, DMSO-d6) delta ppm 3.54 (s, 3H) 3.92 (s, 3H) 7.50 (s, 1H) 7.55 (ddd, J=8.02, 5.87, 2.27 Hz, 1H) 7.60-7.64 (m, 1H) 7.70-7.80 (m, 2H) 7.95 (s, 1H) 8.31 (d, J=7.83 Hz, 1H). LCMS (M+H)+ 240. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With potassium phosphate; palladium diacetate; XPhos; In 1,4-dioxane; water; at 100℃; for 12h;Inert atmosphere; Reflux; | General procedure: Typical procedure 1: a mixture of <strong>[1480-65-5]5-chloro-2-fluoropyridine</strong> 5a(6.60 g, 50.2 mmol), (1-methyl-1H-pyrazol-4-yl)boronic acid(6.30 g, 50.1 mmol), Pd(OAc)2 (0.46 g, 2.1 mmol), 2-dicyclohexylphosphino-20,40,60-triisopropylbiphenyl (1.99 g, 4.1 mmol), and K3PO4 (26.30 g, 123.7 mmol) in dioxane/water (80 mL/8 mL)was stirred at 100 C under N2 atmosphere until the reaction wascompleted by TLC. After the solution was concentrated underreduced pressure, the product was purified via column chromatographyto afford compound 6a (6.80 g, 77percent). 1H NMR (400 MHz,CDCl3, ppm) d 8.22?8.13 (m, 3H), 7.88 (d, J = 0.4 Hz, 1H), 7.30(d, J = 6.8 Hz, 1H) 3.90 (s, 3H). MS m/z (ESI): [M+H]+ 178.1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 80℃; for 10h;Inert atmosphere; | o a 250 ml flask of the three-port adding dioxane (67 ml) and water (27 ml) as the solvent, then adding 3,6- [...] (2.68g, 18mmol), potassium carbonate (6.0g, 43 . 5mmol), 1-methylpyrazole-4-boronic acid pinacone ester (2.99g, 14 . 4mmol), [ 1,1 '-bis (diphenylphosphino) ferrocene] palladium dichloride (0.7g, 0 . 96mmol), after the replacement of nitrogen, raising the temperature to 80 C. Reaction 10 after two hours, concentrating the reaction liquid, column chromatography separation, to obtain strawcoloured solid 3-chloro-6 - (1-methyl -1H-pyrazol-4-yl) pyridazine (HJ-8) 1.96g, yield 70% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In methanol; toluene;Inert atmosphere; Reflux; | General procedure: <strong>[1458-01-1]Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate</strong> 2 (1 eq.) was combined with K2CO3 (10 eq.), the appropriate (het)aryl boronic acid (1.5 eq.) and Pd(PPh3)4 (5 mol%) in a two-neck round bottom flask. The flask was connected to a condenser and purged with nitrogen. A 4:1 mixture of anhydrous toluene: MeOH (60 mL) was added via syringe and the reaction mixture was heated at reflux for 0.5-18 h. The mixture was allowed to cool to room temperature and filtered through Celite (10 x 3 cm, eluting with 3 x 20 mL EtOAc). The filtrate was evaporated to dryness and the residue purified by silica gel flash column chromatography using EtOAc/pet spirit. |
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