Structure of 14631-08-4
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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. : | 14631-08-4 |
Formula : | C4H5ClN4 |
M.W : | 144.56 |
SMILES Code : | NC1=NC(Cl)=NC=C1N |
MDL No. : | MFCD00047355 |
InChI Key : | QDUJVEOOSNUDDW-UHFFFAOYSA-N |
Pubchem ID : | 84565 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 35.85 |
TPSA ? Topological Polar Surface Area: Calculated from |
77.82 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.85 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.14 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.31 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.63 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.28 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.19 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.32 |
Solubility | 6.95 mg/ml ; 0.0481 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.33 |
Solubility | 6.75 mg/ml ; 0.0467 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.53 |
Solubility | 4.3 mg/ml ; 0.0297 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 |
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 |
-7.08 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 |
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) |
1.9 |
* 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 |
---|---|---|
54.5% | With water; iron; ammonium chloride; In ethanol; at 100℃; for 4h; | To a solution of compound 21-2 (20 g, 114.6 mmol) in EtOH/H2O (4/1, 400 mL) was added iron powder (64 g, 1146 mmol) and NH4Cl (aq., 62 g, 1146 mmol), the reaction solution was stirred at 100 C. for 4 h, followed by filtration. The filter cake was washed with MeOH (10 mL×3) and the filtrate was concentrated to give compound 21-3 (9 g, Yield 54.5%) as yellow solid. |
49% | With tin(II) chloride dihdyrate; In ethanol; at 80℃; for 2h;Inert atmosphere; | Step-1: 2-chloropyrimidine-4,5-diamine [0176] A mixture of <strong>[1920-66-7]2-chloro-5-nitropyrimidin-4-amine</strong> (1.0 g, 5.7 mmol) and SnCl2·2H2O (5.2 g, 22.9 mmol) in EtOH (55 mL) under N2 was heated to 80 C and stirred for two hours. The mixture was then concentrated under reduced pressure. EtOAc and Celite were added to the residue and the mixture was basified with saturated Na2CO3 (aq.) to pH 9- 10. The mixture was filtered through a pad of Celite and washed with EtOAc. The organic layer was separated and washed with brine, dried (Na2SO4) and concentrated in vacuum. The residue was purified on ISCO (20 g silica gel column, EtOAc/hexanes 0~100%) to give the title compound (0.41 g, 49%). |
33% | With iron; ammonium chloride; In tetrahydrofuran; ethanol; water;Reflux; | General procedure: Commercial 1a (50mmol) was dissolved in dichloromethane (80mL), mixture was cooled to 0C, solution of NH3 in MeOH (4mol/L, 12.5mL) was added by dripping slowly, after 30min, the mixture maintained at 0C for 1h. The reaction mixture was filtered, and the insoluble material was washed with ethyl acetate (20mL) and water (30mL) to get 2a (8.66g), yield 90%. Compound 2a (50mmol) was dissolved in THF (40mL), then absolute ethyl alcohol (20mL), water (20mL), Fe (4eq) and ammonium chloride (2eq) were added. The mixture was refluxed until raw material disappeared. The reaction mixture was filtered and filter liquor was evaporated by reducing pressure to get 3a (2.4g), yield 33%. Compound 3a (17mmol) was dissolved in DMF (30mL), triethylamine (3eq) was added, and acetyl isothiocyanate (1eq) was added by dripping slowly, the mixture was stirred at room temperature for 30min, then 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI, 1.5eq) was added and stirred overnight at room temperature. Pulled the mixture into ice water, using concentrated HCl regulates pH to 1, the mixture was filtered, the residue was dried and washed by water to give 4a (2.0g), yield 60%. Compound 4a (10mmol), 5a/5b/5c/5d/5e (1.2eq), 120mL 1,4-dioxane, 10mL water, Pd(dppf)Cl2 (0.1eq), and NaHCO3 (1eq) were added to a round-bottomed flask, mixture was stirred for 12h at 90C. Solvent was removed by reduced pressure distillation, residue was purified by preparative HPLC (MeCN+0.05% TFA, H2O 0.1%+TFA), Ta-e were finally obtained from above steps, yield 0.58-5.5%. |
With water; ammonium chloride;iron; In tetrahydrofuran; ethanol; for 3h;Reflux; | (2) The mixture of the above-mentioned product (41 g), reduced iron (52 g), ammonium chloride (25 g), tetrahydrofuran (200 ml), ethanol (100 ml) and water (100 ml) was heated under reflux for 3 hours. The reaction mixture was cooled to room temperature and was filtered through Celite, and ethanol was then evaporated under reduced pressure. The crystals precipitated were collected by filtration and was dried to give 2-chloropyrimidin-4,5-diamine 28 g. 1H-NMR (DMSO-d6) delta: 4.89 (2H, br s), 6.89 (2H, br s), 7.40 (1H, s). |
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