Structure of 64321-24-0
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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. : | 64321-24-0 |
Formula : | C6H6ClN3O |
M.W : | 171.58 |
SMILES Code : | NC(=O)C1=CC=C(Cl)N=C1N |
MDL No. : | MFCD12024435 |
InChI Key : | RZXHKUYBBAQDGZ-UHFFFAOYSA-N |
Pubchem ID : | 22607643 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H317-H319 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 41.75 |
TPSA ? Topological Polar Surface Area: Calculated from |
82.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.71 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.89 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.42 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.01 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.45 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.5 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.8 |
Solubility | 2.71 mg/ml ; 0.0158 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.2 |
Solubility | 1.09 mg/ml ; 0.00636 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.87 |
Solubility | 2.33 mg/ml ; 0.0136 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 |
-6.71 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 |
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) |
1.69 |
* 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 |
---|---|---|
93% | With thionyl chloride In tetrahydrofuran | 2-Amino-6-chloronicotinamide (Inter. 3) To a 0.3 M solution of 2-amino-6-chloronicotinic acid (Inter. 2) (1 equiv) in anhydrous THF, under an inert atmosphere, was added thionyl chloride (3.3 equiv) in a dropwise fashion. The reaction mixture was stirred at room temperature for 2 hours. After this time the reaction was concentrated in vacuo to give a crude yellow solid residue. The crude solid was dissolved in THF (equal to initial reaction volume) and concentrated in vacuo again to give a yellow solid residue. The residue was dissolved once more in THF and concentrated as before to give a solid residue which was then dissolved in THF (to give a solution of 0.3M) and ammonia gas bubbled through the solution for 1 hour. The resultant precipitate was removed by filtration and the filtrate concentrated in vacuo to give a yellow precipitate which was triturated with water at 50° C. then dried to give the title compound (92percent yield, 93percent purity), suitably clean to be used without any further purification. m/z (LC-MS, ESP): 172 [M+H]+R/T=3.19 mins |
92% | Stage #1: With thionyl chloride In tetrahydrofuran at 20℃; for 2 h; Stage #2: With ammonia In tetrahydrofuran for 1 h; |
b) 2-Amino-6-chloronicotinamide (Inter. 3); To a 0.3 M solution of 2-amino-6-chloronicotinic acid (Inter. 2)(1 equiv) in anhydrous THF, under an inert atmosphere, was added thionyl chloride (3.3 equiv) in a dropwise fashion. The reaction mixture was stirred at room temperature for 2 hours. After this time the reaction was concentrated in vacuo to give a crude yellow solid residue. The crude solid was dissolved in THF (equal to initial reaction volume) and concentrated in vacuo again to give a yellow solid residue. The residue was dissolved once more in THF and concentrated as before to give a solid residue which was then dissolved in THF (to give a solution of 0.3M) and ammonia gas bubbled through the solution for 1 hour. The resultant precipitate was removed by filtration and the filtrate concentrated in vacuo to give a yellow precipitate which was triturated with water at 50°C then dried to give the title compound (92percent yield, 93percent purity), suitably clean to be used without any further purification, m/z (LC- MS, ESP): 172 [M+H]+ R/T = 3.19 mins |
90% | Stage #1: With thionyl chloride In tetrahydrofuran at 20℃; for 2 h; Stage #2: With ammonia In tetrahydrofuran for 1 h; |
To a 0.3 M solution of amino acid (1 equiv) in anhydrous THF, under an inert atmosphere, was added thionyl chloride (3.3 equiv) in a dropwise fashion. The reaction mixture was stirred at room temperature for 2 hours. After this time the reaction was concentrated in vacuo to give a crude yellow solid residue. The crude solid was dissolved in THF (equal to initial reaction volume) and concentrated in vacuo again to give a yellow solid residue. The residue was dissolved once more in THF and concentrated as before to give a solid residue which was then dissolved in THF (to give a solution of 0.3M) and ammonia gas bubbled through the solution for 1 hour. The resultant precipitate was removed by filtration and the filtrate concentrated in vacuo to give a yellow precipitate which was triturated with water at 50 0C then dried to give the title compound (typically 90-95 percent) yield and suitably clean enough to be used without any further purification.2-Amino-6-chloronicotinamide - X=N, Y=C, Z=C: (92 percent yield, 93 percent purity) m/z (LC-MS, ESP): 172 [M+H]+ R/T = 3.19 min |
81% | With ammonium chloride; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In N,N-dimethyl-formamide at 25℃; for 16 h; | To a solution of 2-amino-6-chloronicotinic acid (1.0 g, 5.79 mmol), HOBT (932 mg, 6.95 mmol) and EDCI (2.22 g, 11.6 mmol) in 15 mL of DMF was added triethylamine (5.86 g, 57.9mmol) and NH4C1 (1.55 g, 28.9 mmol). Then the mixture was stirred at room temperature for 16 h. The solution was concentrated in vacuo to remove DMF and the residue was suspended in saturated NaHCO3. Finally the 2-amino-6-chloronicotinamide (800 mg, yield: 81percent) was obtained by filtration without further purification. ‘H-NMR (DMSO-d6, 400 MHz) 7.95 (d, J = 8.4 Hz, 1H), 7.62 (s, 2H), 7.39 (s, 2H), 6.59 (d, J = 8.4 Hz, 1H). MS (M+H): 172 / 174. |
78% | With thionyl chloride In 1,2-dichloro-ethane; N,N-dimethyl-formamide | Example 140B 2-Amino-6-chloro-nicotinamide To a mixture of Example 140A (11.9 g, 69.2 mmol) in 1,2-dichloroethane (100 mL) was added thionyl chloride (30 mL, 411 mmol) and DMF (catalytic). The mixture was refluxed for 4 h then evaporated. The residue was taken in ether (200 mL) and ammonia was bubbled through for 15 min. The mixture was stirred overnight at rt then washed with water (100 mL) and brine (100 ml). The ether was evaporated off to yield 9.2 g of product (78percent). MS (DCI/NH3) m/z 172 (M+1)+. |
78% | Stage #1: With thionyl chloride In 1,2-dichloro-ethane for 4 h; Heating / reflux Stage #2: With ammonia In diethyl ether at 20℃; |
Example 140B 2-Amino-6-chloro-nicotinamide To a mixture of Example 140A (11.9 g, 69.2 mmol) in 1,2-dichloroethane (100 mL) was added thionyl chloride (30 mL, 411 mmol) and DMF (catalytic). The mixture was refluxed for 4 h then evaporated. The residue was taken in ether (200 mL) and ammonia was bubbled through for 15 min. The mixture was stirred overnight at rt then washed with water (100 mL) and brine (100 ml). The ether was evaporated off to yield 9.2 g of product (78percent). MS (DCI/NH3) m/z 172 (M+1)+. |
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