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Type | HazMat fee for 500 gram (Estimated) |
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Structure of 1780-31-0
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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. : | 1780-31-0 |
Formula : | C5H4Cl2N2 |
M.W : | 163.00 |
SMILES Code : | CC1=CN=C(Cl)N=C1Cl |
MDL No. : | MFCD00023197 |
InChI Key : | DQXNTSXKIUZJJS-UHFFFAOYSA-N |
Pubchem ID : | 74508 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H314 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Class: | 8 |
UN#: | 3265 |
Packing Group: | Ⅱ |
Num. heavy atoms | 9 |
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 | 37.02 |
TPSA ? Topological Polar Surface Area: Calculated from |
25.78 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.96 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.49 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.09 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.16 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.67 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.07 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.91 |
Solubility | 0.199 mg/ml ; 0.00122 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.68 |
Solubility | 0.343 mg/ml ; 0.00211 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.26 |
Solubility | 0.0892 mg/ml ; 0.000547 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 |
-5.53 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) |
1.6 |
* 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 |
---|---|---|
22% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 140℃; for 0.25h;sealed tube; microwave irradiation; | [0163] To a microwave reaction tube was charged with 2,4-dichloro-5-methyl-pyrimidine (0.50 g, 3.1 mmol), <strong>[338454-45-8]5-hydroxymethylthiophene-2-boronic acid</strong> (0.60 g, 3.8 mmol) and Pd(PPh3 )4 (0.20 g, 0.17 mmol). DMF (6 mL) was added to the above mixture followed by aqueous sodium carbonate (2 M; 3.0 mL, 6.0 mmol). The reaction tube was sealed and the suspension irradiated with microwave at 140 0C for 15 min. After cooling to room temperature, the mixture was filtered and the filtered solid washed with DCM. The filtrate was concentrated and the residue purified by column chromatography on silica gel (hexanes to 70% EtOAc/hexanes) to afford the title compound as an off white solid (0.16 g, 22%). MS (ES+): m/z 241 (M+H)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With potassium carbonate; In acetonitrile; at 80℃; for 3h; | To a solution of ethyl 3-methyl-iH-pyrazole-4-carboxylate (4.7 g, 30.6 mmol) in acetonitrile were added potassium carbonate (10.6 g, 75.0 mmol) and 2,4-dichloro- 5-methylyrimidine (5.0 g, 30.6 mmol) at room temperature. The resulting suspension was heated at 80 C for 3 hours with monitoring a reaction with LC-MS or thin layer chromatography (TLC). Volatiles were partially removed and the residue was extracted with ethyl acetate. The collected organic layer was washed with brine, dried over anhydrous sodium sulfate and then concentrated in vacuo. The resulting solid was recrystallized in a mixture of heptanes and ethyl acetate to afford the desired intermediate 5 as a pale yellow solid (5.2 g, 61 %); MS (ESI) mJz 281 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With N-ethyl-N,N-diisopropylamine; In ethanol; for 24h;Reflux; | 2-Chloro-^4-[3-(1 -dimethylethyl)phenyl]-5-methylpyrimidin-4-amine (SG2-013): A solution of 2,4-dichloro-5-methylpyrimidine (0.500 g), 3-(tert-butyl)aniline (0.458 mg), and DIPEA (3.21 mL) in EtOH (2.5 mL) was heated at reflux for 24 h. The mixture was concentrated under reduced pressure. The resulting residue was dissolved in EtOAc (25 mL), washed with water (2 x 25 mL) and brine (25 mL). The organic layer was dried ( a2S04) and concentrated under reduced pressure to give the title compound as an off-white solid (0.564 g, 67percent). Mp: 174-175 °C. NMR (400 MHz, DMSO-): delta 8.80 (s, IH, reduced by 50percent on D2O shake), 8.01 (s, IH), 7.65 (t, J= 1.9 Hz, IH), 7.47 (ddd, J= 7.8, 1.9, 1.0 Hz, IH), 7.26 (t, J= 7.8 Hz, IH), 7.12 (ddd, J= 7.8, 1.9, 1.0 Hz, IH), 2.15 (s, 3H), 1.27 (s, 9H). HPLC-MS (ESI+): m/z 278.1 [40percent, (M37C1+H)+], 276.1 [100percent, (M35C1+H)+]. |
67% | With N-ethyl-N,N-diisopropylamine; In ethanol; for 24h;Reflux; | A solution of 2,4-dichloro-5-methylpyrimidine (0.500 g), 3-(i |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In water; acetonitrile; for 18h;Reflux; Inert atmosphere; | General procedure: A RBF was charged with 2, 4-dichloropyrimindine (784mg, 5.2mmol, 1 equiv.), compound 48 (1.5g, 5.74 mmol, 1.1 equiv.), Pd(PPh3)4 (250mg, 0.226mmol, 0.05 equiv.) and sodium carbonate (991mg, 9.36mmol, 1.8 equiv.) MeCN: H2O (9: 1, 40mL) were added into the RBF and the reaction mixture was degassed under N2, stirred and refluxed overnight under N2. The reaction was cooled, and the reaction mixture was concentrated under vacuum. EA and water were added for extraction. By collecting the organic layer and evaporating solvent, a light yellow crude product was obtained, which was purified using flash chromatography (elution system - EA/Hexane=1: 1 to MeOH/EA=2: 98) to give 5 a light yellow solid (1.25g, 97%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
31% | With triethylamine; In acetonitrile; at 20℃; | 2,4-dichloro-5-methylpyrimidine (2.00 g, 12.3 mmol) was added to a solution of <strong>[133773-29-2](1R)-1-(2,4-dichlorophenyl)ethanamine</strong> (2.33 g, 12.3 mmol) and triethylamine (2.57 mL, 18.4 mmol) in acetonitrile (40.0 mL) and the mixture was stirred at room temperature overnight. The mixture was evaporated then loaded onto silica gel using 5 mL of (0596) dichloromethane, and the crude product was purified by flash column chromatography (0- 60% EtOAc/hexanes) yielding (R)-2-chloro-N-(1-(2,4-dichlorophenyl)ethyl)-5- methylpyrimidin-4-amine (1.20 g, 31% yield). [M+H] = 315.9 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | at 20.0℃; for 12.0h; | To a solution of 2,4-dichloro-5-methylpyrimidine (12.8 g, 80 mmol, 1 equiv) in MeOH (30 mL) was added NaOMe (5 mol/L in MeOH, 14.8 mL, 74 mmol, 0.9 equiv) dropwise. The reaction mixture was stirred at room temperature for 12 hours and concentrated. The residue was charged with H2O (30 mL) and extracted with DCM (3 * 80 mL). The combined organic phase were washed with brine (30 mL), dried over anhydrous Na2S04 and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (eluted with PE/EtOAc = 100/1) to afford the title compound 2-chloro-4- methoxy-5-methylpyrimidine as a white solid (9.3 g, 74% yield). LC-MS: m/z 159.1 (M+H)+. |
62% | for 20.0h; | 5.4M Sodium methoxide in MeOH (1.14 mL) was added to a suspension of 2,4-dichloro-5-methylpyrimidine (1.0 g, 6.1 mmol) in MeOH (20 mL) and the reaction stirred for 20 h. The mixture was concentrated and the residue partitioned between EtOAc and water. The aqueous layer was extracted into EtOAc (x3), the combined organics washed with brine, dried (MgSO4) and concentrated. The residue was purified by Biotage Isolera chromatography (silica gel, eluting with 0-50% EtOAc in heptane to yield 600 mg (62% yield) of the title compound as a white solid. 1H NMR (500 MHz, CDCl3) d 8.10 (s, 1H), 4.03 (s, 3H), 2.12 (d, J = 0.7 Hz, 3H). LCMS (Analytical Method D) Rt= 1.00, MS (ESIpos): m/z= 158.9 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With N-ethyl-N,N-diisopropylamine; In isopropyl alcohol;Reflux; | General procedure: A mixture of substituted 2,4-dichloropyrimidine (1.0 equiv.), and substituted aniline (1.0-1.05 equiv.), and DIPEA (1.2 equiv.) in isopropanol (0.1 M) was stirred and heated at reflux. The reaction time, work-up, and product isolation procedure are described below. |
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