Structure of 63069-50-1
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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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Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 63069-50-1 |
Formula : | C7H5FN2 |
M.W : | 136.13 |
SMILES Code : | C1=C(C=CC(=C1F)N)C#N |
MDL No. : | MFCD00055559 |
InChI Key : | RLMBRRQWBTWGMB-UHFFFAOYSA-N |
Pubchem ID : | 2756431 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P301+P312-P302+P352-P304+P340-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 35.52 |
TPSA ? Topological Polar Surface Area: Calculated from |
49.81 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.24 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.16 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.71 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.22 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.5 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.37 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.86 |
Solubility | 1.88 mg/ml ; 0.0138 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.8 |
Solubility | 2.15 mg/ml ; 0.0158 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.37 |
Solubility | 0.578 mg/ml ; 0.00425 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) |
Yes |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.31 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) |
1.45 |
* 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 |
---|---|---|
88% | With N-chloro-succinimide; In acetonitrile; at 85℃; for 5.0h; | 4-Amino-3-chloro-5-fluorobenzonitrile A mixture of 4-amino-3-fluorobenzonitrile (1 equiv.) and N-chlorosuccinimide (1.5 equiv.) in acetonitrile (0.24 M) was stirred at 85 C. for 5 h. The solvent was removed by concentration and the residue was partitioned between ethyl acetate and 5% NaOH. The organic phase was washed with 5% NaOH and brine. Then the organic phase was dried over MgSO4 and dried in vacuum to afford 4-amino-3-chloro-5-fluorobenzonitrile (88%) as a beige solid. 1H NMR (400 MHz, CDCl3) delta ppm: 7.41 (t, J=6 Hz, 1H), 7.24 (dd, J=1.8, 10.2 Hz, 1H), 4.66 (s, 2H). |
With N-chloro-succinimide; In acetonitrile; at 86℃; for 6.0h; | INTERMEDIATE 74-Amino-3-chloro-5-fluorobenzonitrile A solution of 4-amino-3-fluorobenzonitrile (25.13 g, 185 mmol) and NCS (24.65 g, 185 mmol) in acetonitrile (500 mL) was stirred at 86 C (reflux) for 5 h. LCMS showed -17% of starting material remained. Additional NCS (0.2 eq) was added and the reaction was stirred for 1 h. The reaction was partly concentrated and the residue was partitioned between 5% NaOH (100 mL) and EtOAc. The aqueous layer was back extracted with EtOAc. The organic extracts were dried over Na2S04 and concentrated to a pink solid. The NMR spectrum showed some of the succinimate side product still remained. The crude product was washed with H20 and air dried to give the desired product as a beige solid. This product was used in the next step without any futher purification. MS (m/z) 171.1 (M+H+). | |
With N-chloro-succinimide; In acetonitrile; at 86℃; for 6.0h; | 4-Amino-3-chloro-5-fluorobenzonitrileA solution of 4-amino-3-fluorobenzonitrile (25.13 g, 185 mmol) and NCS (24.65 g, 185 mmol) in acetonitrile (500 mL) was stirred at 86 C (reflux) for 5 h. LCMS showed -17% of starting material remained. Additional NCS (0.2 eq) was added and the reaction was stirred for 1 h. The reaction was partly concentrated and the residue was partitioned between 5% NaOH (100 mL) and EtOAc. The aqueous layer was back extracted with EtOAc. The organic extracts were dried over Na2S04 and concentrated to a pink solid. The NMR spectrum showed some of the succinimate side product still remained. The crude product was washed with H20 and air dried to give the desired product as a beige solid. This product was used in the next step without any futher purification. MS (m/z) 171.1 (M+H+). |
With N-chloro-succinimide; acetic acid; at 70℃; for 16.0h; | 1.13. Synthesis of 4-amino-3-chloro-5-fluoro-benzonitrile (Int.21) A mixture of 4-amino-3-fluorobenzonitrile (184 mmol) and NCS (276 mmol) in AcOH (300 mL) was stirred at 70 C. for approximately 16 h. The mixture was concentrated. H2O was added to the residue and the solid product was filtered off and washed (sat. NaHCO3 and H2O). To eliminate H2O, THF was added and removed under reduced pressure to yield the desired product. | |
With N-chloro-succinimide; acetic acid; at 70℃; for 16.0h; | 1.13. Synthesis of 4-amino-3-chloro-5-fluoro-benzonitrile (mt. 21) j00260j A mixture of 4-amino-3-fluorobenzonitrile (184 mmol) and NCS (276 mmol) in AcOH (300 mL) was stirred at 70C for approximately 16 h. The mixture was concentrated. H20 was added to the residue and the solid product was filtered off and washed (sat. NaHCO3 and H20). To eliminate H20, THF was added and removed under reduced pressure to yield the desired product. | |
With N-chloro-succinimide; acetic acid; at 70℃; for 0.16h; | A mixture of 4-amino-3-fluorobenzonitrile (184 mmol) and NCS (276 mmol) in AcOH (300 mE) was stirred at 70 C. for approximately 16 h. The mixture was concentrated. H20 was added to the residue and the solid product was filtered oil and washed (sat. NaHCO3 and H20). To eliminate H20, THF was added and removed under reduced pressure to yield the desired product. | |
With N-chloro-succinimide; In acetic acid; at 70℃; for 16.0h; | 3.123. Compound 111: (lR,2R)-N-[6-(2-chloro-4-cyano-6-fluoro-N-methyl-anilino)-l-methyl- 3.123.1. Step i): 4-amino-3-chloro-5-fluoro-benzonitrile A mixture of 4-amino-3-fluorobenzonitrile (184 mmol) and NCS (276 mmol) in AcOH (300 mL) is stirred at 70C for approximately 16 h. The mixture is concentrated. H20 is added to the residue and the solid product is filtered off and washed (sat. NaHCC>3 and H20). To eliminate H20, THF is added and removed under reduced pressure to yield the desired product (Int. 21). 3.123.2. Step ii): 4-[[6-[bis[(4-methoxyphenyl)methyl]amino]-4-(methylamino)-5-nitro-2- pyridyl]amino]-3-chloro-5-fluoro-benzonitrtte |
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