Structure of 4316-94-3
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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. : | 4316-94-3 |
Formula : | C4H3ClN4O2 |
M.W : | 174.55 |
SMILES Code : | C1=NC(=C([N+]([O-])=O)C(=N1)N)Cl |
MDL No. : | MFCD00127772 |
InChI Key : | BWLOHIMQWHFSQF-UHFFFAOYSA-N |
Pubchem ID : | 101229 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 40.27 |
TPSA ? Topological Polar Surface Area: Calculated from |
97.62 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.57 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.53 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.63 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-1.08 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-1.07 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.12 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.22 |
Solubility | 1.04 mg/ml ; 0.00597 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.19 |
Solubility | 0.113 mg/ml ; 0.000647 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.29 |
Solubility | 9.01 mg/ml ; 0.0516 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 |
-6.28 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 |
2.0 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) |
2.02 |
* 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 |
---|---|---|
87.6% | With tris-(dibenzylideneacetone)dipalladium(0); potassium carbonate; (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl; In acetonitrile; at 25℃; for 3.5h;Inert atmosphere; | General procedure: 6-Chloro-5-nitropyrimidine-4-amine (0.5mmol), amine (1.5mmol), Pd2(dba)3 (0.01mmol), R-BINAP (0.03mmol) and potassium carbonate (0.7mmol) were dissolved in acetonitrile (5mL). The solution was stirred at room temperature for 3.5h under an argon atmosphere. The resulting reaction mixture was treated with saturated brines (50mL) and extracted with acetonitrile (3×25mL), and dried with anhydrous Na2SO4. The anhydrous Na2SO4 was removed by filtration and the filtrate was concentrated. The residue was washed with ethyl acetate (3×2mL) and diethyl ether (3×2mL), filtered and dried under vacuum. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92.2% | With tris-(dibenzylideneacetone)dipalladium(0); potassium carbonate; (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl; In acetonitrile; at 25℃; for 3.5h;Inert atmosphere; | General procedure: 6-Chloro-5-nitropyrimidine-4-amine (0.5mmol), amine (1.5mmol), Pd2(dba)3 (0.01mmol), R-BINAP (0.03mmol) and potassium carbonate (0.7mmol) were dissolved in acetonitrile (5mL). The solution was stirred at room temperature for 3.5h under an argon atmosphere. The resulting reaction mixture was treated with saturated brines (50mL) and extracted with acetonitrile (3×25mL), and dried with anhydrous Na2SO4. The anhydrous Na2SO4 was removed by filtration and the filtrate was concentrated. The residue was washed with ethyl acetate (3×2mL) and diethyl ether (3×2mL), filtered and dried under vacuum. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91.2% | With tris-(dibenzylideneacetone)dipalladium(0); potassium carbonate; (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl; In acetonitrile; at 25℃; for 3.5h;Inert atmosphere; | General procedure: 6-Chloro-5-nitropyrimidine-4-amine (0.5mmol), amine (1.5mmol), Pd2(dba)3 (0.01mmol), R-BINAP (0.03mmol) and potassium carbonate (0.7mmol) were dissolved in acetonitrile (5mL). The solution was stirred at room temperature for 3.5h under an argon atmosphere. The resulting reaction mixture was treated with saturated brines (50mL) and extracted with acetonitrile (3×25mL), and dried with anhydrous Na2SO4. The anhydrous Na2SO4 was removed by filtration and the filtrate was concentrated. The residue was washed with ethyl acetate (3×2mL) and diethyl ether (3×2mL), filtered and dried under vacuum. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98.9% | With tris-(dibenzylideneacetone)dipalladium(0); potassium carbonate; (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl; In acetonitrile; at 25℃; for 3.5h;Inert atmosphere; | General procedure: 6-Chloro-5-nitropyrimidine-4-amine (0.5mmol), amine (1.5mmol), Pd2(dba)3 (0.01mmol), R-BINAP (0.03mmol) and potassium carbonate (0.7mmol) were dissolved in acetonitrile (5mL). The solution was stirred at room temperature for 3.5h under an argon atmosphere. The resulting reaction mixture was treated with saturated brines (50mL) and extracted with acetonitrile (3×25mL), and dried with anhydrous Na2SO4. The anhydrous Na2SO4 was removed by filtration and the filtrate was concentrated. The residue was washed with ethyl acetate (3×2mL) and diethyl ether (3×2mL), filtered and dried under vacuum. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With water; iron;hydrogenchloride; In ethanol; at 85℃;Industry scale; | 6-ChJoropyrimidine-4,5-diamine[00162] Iron dust (1000 g, 17.9 mol) was added to a solution of the crude 6-chloro-5- nitropyrimidin-4-amine (500 g, 2.87 mol) in ethanol (5000 mL) and water (1000 mL). A catalytic amount of concentrated hydrochloric acid (10 mL) was slowly added to the reaction mixture over a period of 20 minutes. During the course of the addition the reaction temperature was observed to increase to 85 C without external heating and the reaction mixture's color changed from yellow-brown to dark red. After the reaction mixture had cooled down to a temperature of 50 C, the slurry was filtered through a Celite pad, which was then washed with ethanol (3 x 250 mL). The resulting filtrate was concentrated under reduced pressure to give a yellow solid. This solid was then washed with hexane and dried under reduced pressure to give the title compound as a brown solid. (253 g, overall yield over two steps: 37.1% yield). NMR (400 MHz, DMSO-d6): 6 7.61 (s, 1H), 6.71 (broad s, 2H), 4.94 (broad s, 2H). MS (EI) for C4H5C1N4: 145 (MU+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With ammonium hydroxide; sodium hydrogencarbonate; In tetrahydrofuran; at 55℃; | To a solution of the compound 4,6-dichloro-5-nitropyrimidine (9.7 g, 50 mmol) in tetrahydrofuran (100 mL) was added aqueous ammonia (100 mL) and sodium bicarbonate (4.6 g, 55 mmol), heated to 55 C and stirred overnight. The reaction was cooled to room temperature and the organic solvent was removed under reduced pressure. The residue was filtered and separated by flash column chromatography (dichloromethane: methanol = 100: 1) to give the title compound A: 6-chloro-5-nitropyrimidine- 4-amine (8.1 g, yield 93%). |
With ammonium hydroxide; In methanol; diethyl ether; water; for 2.0h;Industry scale; | 6-Chloro-5-nitropyrimidin-4-amine[00161] A solution of 28% aqueous ammonium hydroxide (670 mL, 5.35 mol, 1.04 equiv) was added in a drop-wise fashion to a rapidly stirred solution of the 4,6-dichloro-5- nitropyrimidine solid (1000 g, 5.16 mol, 1.00 equiv) in diethyl ether (4000 mL) and methanol (670 mL). The addition was carried out over a period of 2 hours. Upon completion of addition, the resulting yellow solid was filtered off, washed with water and hexane, and dried under reduced pressure to give the title compound as a yellow solid (yield: 675 g). This crude solid was used in the next step without any further purification. NMR (400 MHz, DMSO- d6): delta 8.97 (s, 1H), 7.91 (broad s, 2H). MS (EI) for C4H3CIN4O2: 175 (MH+). |