Structure of 4994-86-9
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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. : | 4994-86-9 |
Formula : | C5H5ClN2 |
M.W : | 128.56 |
SMILES Code : | C1=C(N=C(N=C1)C)Cl |
MDL No. : | MFCD00234069 |
InChI Key : | WDTVJRYCMIZPMX-UHFFFAOYSA-N |
Pubchem ID : | 424447 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319 |
Precautionary Statements: | P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313 |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.2 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 32.01 |
TPSA ? Topological Polar Surface Area: Calculated from |
25.78 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.78 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.56 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.44 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.54 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.04 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.47 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.17 |
Solubility | 0.859 mg/ml ; 0.00669 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.71 |
Solubility | 2.5 mg/ml ; 0.0194 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.62 |
Solubility | 0.311 mg/ml ; 0.00242 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 |
-5.98 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) |
1.43 |
* 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 |
---|---|---|
INTERMEDIATE 59 4-(3-Iodo-lH-pyrazol-l -yl)-2-methylpyrimidine To a solution of 3-iodo-lH-pyrazole (500 mg, 2.58 mmol) in anhydrous DMSO (6 mL) was added NaH (155 mg, 3.87 mmol) at 0 C. The mixture was stirred for 30 min at 0 C, followed by the addition of 4-chloro-2-methylpyrimidine (331 mg, 2.58 mmol) in DMSO (2 mL). The resulting mixture was stirred at 90 C overnight. The mixture was cooled to room temperature, quenched with water (10 mL) and extracted EtOAc (40 mL x 3). The organic layer was collected and dried over Na2S04. The solvent was removed in vacuo to give the crude product. This was purified by flash chromatography (ISCO Combiflash, 24 g, Biotage Si column, -60 mL/min, 100% hexanes 5 min, gradient to 100% EtOAc in hexanes 15 min) to afford 4-(3-iodo-17J- pyrazol-l-yl)-2-methylpyrimidine. LCMS calc. = 286.98; found = 286.95 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With chloro(2-dicyclohexylphosphino-2?,4?,6?-triisopropyl-1,1?-biphenyl)[2-(2?-amino-1,1?-biphenyl)]palladium(II); caesium carbonate; In 1,4-dioxane; water; at 80℃; for 1.0h;Inert atmosphere; | A stirred solution of 4-chloro-2-methylpyrimidine (100 mg, 0.778 mmol), CS2CO3 (507 mg, 1.556 mmol), <strong>[904326-92-7](6-fluoro-5-methylpyridin-3-yl)boronic acid</strong> (121 mg, 0.778 mmol) in a mixture of 1 ,4-dioxane (6 mL) and water (0.5 mL) was purged with nitrogen for 3 min. XPhos 2nd generation precatalyst (61.2 mg, 0.078 mmol) was added in one portion and the reaction mixture was heated to 80 C and stirred for 1 h. The reaction mixture was allowed to cool to room temperature. Water (20 mL) was added and the solution was extracted with EtOAc (2 x 30 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (EtOAc in hexanes) to afford 4-(6-fluoro-5-methylpyridin-3-yl)-2-methylpyrimidine (115 mg, 0.521 mmol, 67% yield) as an off-white solid. LCMS (ESI) m/e 204.2 [(M+H)+, calcd for C11H11FN3, 204.1]; LC/MS retention time (method Al) to = 1.90 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36.40% | With caesium carbonate; In N,N-dimethyl-formamide; at 100℃; for 4h; | To a solution of <strong>[20901-53-5]methyl 2-oxo-2,3-dihydro-1H-imidazole-4-carboxylate</strong> (1.50 g, 10.55 mmol) in DMF (30 mL) was added 4-chloro-2-methylpyrimidine (1.63 g, 12.67 mmol) followed by Cs2CO3 (6.88 g, 21.11 mmol) and the resulting reaction mixture was heated at 100 C for 4 h. The reaction mixture was cooled to ambient temperature, concentrated to dryness under reduced pressure and diluted with water (50 mL). The solid precipitate obtained was filtered and dried under vacuum to afford Intermediate 95A (1.20 g, 36.40%).1H NMR (400 MHz, DMSO-d6) G ppm 2.67 (s, 3 H), 3.82 (s, 3 H), 7.85 (s, 1 H), 8.3 (d, 6.0 Hz, 1 H), 8.6 (d, 6.0 Hz, 1 H), (1 Exchangeable proton was not observed). LCMS (Method-D): retention time 1.06 min, [M+1] 235.2 |
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