Structure of 147362-88-7
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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. : | 147362-88-7 |
Formula : | C9H12ClN3O |
M.W : | 213.66 |
SMILES Code : | CC(C)(C)C(NC1=NN=C(Cl)C=C1)=O |
MDL No. : | MFCD17015221 |
InChI Key : | ZZJOBCNIMHAKDP-UHFFFAOYSA-N |
Pubchem ID : | 10899975 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H320-H335 |
Precautionary Statements: | P261-P280-P301+P312-P302+P352-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.44 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 55.52 |
TPSA ? Topological Polar Surface Area: Calculated from |
54.88 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.72 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.92 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.1 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.71 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.69 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.37 |
Solubility | 0.917 mg/ml ; 0.00429 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.49 |
Solubility | 0.694 mg/ml ; 0.00325 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.49 |
Solubility | 0.0698 mg/ml ; 0.000327 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 |
-6.38 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 |
0.0 |
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) |
2.14 |
* 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 |
---|---|---|
tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 100.0℃; for 2.5h; | A flask was charged with <strong>[147362-88-7]N-(6-chloro-pyridazin-3-yl)-2,2-dimethyl-propionamide</strong> (Turck. Alain; PIe, Nelly; Ndzi, Bruno; Queguiner, Guy; Haider, Norbert Schuller, Herbert; Heinisch, Gottfried. Tetrahedron. 1993, 49, 599-606.) (500 mg, 2.34 mmol), Pd(PPh3)4 (811 mg, 0.701 mmol), and Zn(CN)2 (192 mg, 1.64 mmol) and placed under a nitrogen atmosphere. DMF (25 mL) was added to the flask and the reaction mixture was heated at 100 oC for 2.5 h. The reaction mixture was cooled and poured into H2O (100 mL) and EtOAc (100 mL), An emulsion formed and the mixture was filtered through a short plug of celite and then the layers were separated. The organic layer was washed with H2O (100 mL), dried (MgSO4), filtered, concentrated, and purified by chromatography (loaded with CH2CI2, eiuted with a gradient of 10-30% EtOAc in hexanes) to provide 329 mg of N-(6-cyano-pyridazin-3-yl)- 2,2-dimethyl-propionamde as a pale yellow solid. MS: (M+) 205. 1H NMR (400 MHz, CDCl3): delta 8.71 (bs, 1), 8.65 (d, 1, J = 9.3), 7.80 (d, 1, J = 9.3), 1.36 (s, 9). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine; In dichloromethane; at 20.0℃; for 2.0h; | General procedure: Step 2: 2,2-Dimethyl-N-(5-phenylethynyl-pyridin-2-yl)-propionamide [0122]5-Phenylethynyl-pyridin-2-ylamine (Example 1, step 1) was dissolved in dichloromethane (3 ml). Pyridine (52 mg, 53 mul, 0.67 mmol, 2 equiv.) and pivaloyl chloride (48 mg, 50 mul, 0.40 mmol, 1.2 equiv.) were added and the mixture was stirred for 2 hours at room temperature. The reaction mixture was extracted with 1N HCl solution and twice with dichloromethane. The organic extracts were combined, dried over sodium sulfate and evaporated to dryness. The crude product was purified by flash chromatography on a silica gel column eluting with heptane:dichloromethane 50:50. The desired 2,2-dimethyl-N-(5-phenylethynyl-pyridin-2-yl)-propionamide (40 mg, 43% yield) was obtained as a light yellow solid, MS: m/e=279.3 (M+H+). | |
With pyridine; In dichloromethane; at 20.0℃; for 2.0h; | General procedure: Step 2 : 2,2-Dimethyl-N-(5 -phenylethynyl-pyridin-2-yl)-propionamide (65 mg, 0.33 mmol) 5-Phenylethynyl-pyridin-2-ylamine (Example 1, step 1) was dissolved in dichloromethane (3 ml). Pyridine (52 mg, 53 mu, 0.67 mmol, 2 equiv.) and pivaloyl chloride (48 mg, 50 mu, 0.40 mmol, 1.2 equiv.) were added and the mixture was stirred for 2 hours at room temperature. The reaction mixture was extracted with IN HC1 solution and twice with dichloromethane. The organic extracts were combined, dried over sodium sulfate and evaporated to dryness. The crude product was purified by flash chromatography on a silica gel column eluting with heptane: dichloromethane 50:50. The desired 2,2-dimethyl-N-(5-phenylethynyl- pyridin-2-yl)-propionamide (40 mg, 43 % yield) was obtained as a light yellow solid, MS: m/e = 279.3 (M+H+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | at 120.0℃; for 24.0h; | mixture of<strong>[147362-88-7]N-(6-chloro-3-pyridazinyl)-2,2-dimethylpropanamide</strong> (65.3 g; 305.6 mmol) and morpholine (538 mL; 6.1 mmol) was heated at 120 C for 24 hours. The mixture was cooled and evaporated. The residue was poured into cooled water, basified with K2C03 powder and DCM was added. The organic layer was separated, dried over MgS04, filtered and evaporated to dryness. The residue was crystallized from Et20. The precipitate was filtered and dried to afford 69.3 g (87%) of intermediate 18. |
87% | at 120.0℃; for 24.0h; | A mixture of <strong>[147362-88-7]N-(6-chloro-3-pyridazinyl)-2,2-dimethylpropanamide</strong> (65.3 g; 305.6 mmol) and morpholine (538 mL; 6.1 mmol) was heated at 120 C for 24 hours. The mixture was cooled and evaporated. The residue was poured into cooled water, basified with K2CO3 powder and DCM was added. The organic layer was separated, dried over MgSOzi, filtered and evaporated to dryness. The residue was crystallized from Epsilon2Omicron. The precipitate was filtered and dried to afford 69.3 g (87%) of intermediate 58. |