Structure of 3430-22-6
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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. : | 3430-22-6 |
Formula : | C6H6BrN |
M.W : | 172.02 |
SMILES Code : | C1=CN=CC(=C1C)Br |
MDL No. : | MFCD00082592 |
InChI Key : | GSQZOLXWFQQJHJ-UHFFFAOYSA-N |
Pubchem ID : | 817630 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.17 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 36.9 |
TPSA ? Topological Polar Surface Area: Calculated from |
12.89 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.83 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.91 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.15 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.58 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.54 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.0 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.66 |
Solubility | 0.372 mg/ml ; 0.00216 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.8 |
Solubility | 2.7 mg/ml ; 0.0157 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.26 |
Solubility | 0.0948 mg/ml ; 0.000551 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 |
-5.99 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) |
1.19 |
* 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 |
---|---|---|
66% | With triethylamine;1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; In N,N-dimethyl-formamide; at 70 - 80℃; under 2585.81 Torr; for 10h; | 4-Methyl-nicotinic acid methyl ester Triethylamine (45 g, 0.45 mol) was added into the mixture of compound 3-bromo-4-methyl-pyridine (25 g, 0.15 mol), Pd(OAc)2 (3.37 g, 0.015 mol) and dppf (6.19 g, 0.015 mol) in DMF/MeOH (150 mL/150 mL) dropwise. Then the mixture was heated to 70~80 C. under 50 psi of CO for 10 hours. The reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica gel (petroleum ether/ethyl acetate=10:1) to afford 15 g of 4-methyl-nicotinic acid methyl ester as a yellow oil in 66% yield. |
66% | With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; triethylamine; In N,N-dimethyl-formamide; at 70 - 80℃; under 2585.81 Torr; for 10h; | Trieithylamine (45 g, 0.45 mol) was added into the mixture of compound 3-bromo-4-methyl-pyridine (25 g, 0.15 mol), Pd(OAc)2 (3.37 g, 0.015 mol) and dppf (6.19 g, 0.015 mol) in DMF/MeOH (150 mL/150 mL) dropwise. Then the mixture was heated to 70?80 C. under 50 psi of CO for 10 hours. The reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica gel (petroleum ether/ethyl acetate=10:1) to afford 15 g of 4-methyl-nicotinic acid methyl ester as a yellow oil in 66 % yield. |
51% | With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; triethylamine; In N,N-dimethyl-formamide; at 140℃; under 22502.3 Torr;Autoclave; | A metal reactor was charged with 3-bromo-4-methyl-pyridine (200 g, 0.116 mol) and a mixture of DMF/MeOH (1 L/1L). To this was added Et3N (400 g, 0.395 mol), palladium (II) acetate (8 g, 0.036 mol) and 1,1'- bis(diphenylphosphino)ferrocene (16 g, 0.029 mol). The reactor was closed and pressurized with CO gas (3 MPa) and the reaction mixture was stirred and heated overnight at 140 C. The RM was cooled, filtered and concentrated in vacuo. The residue was purified by flash column chromatography over silica gel (gradient eluent: EtO Ac/Petroleum ether from 1/1 to 1/0). The product fractions were collected and the solvent was evaporated to afford the desired intermediate 1 (90 g, 51%). |
51% | With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; triethylamine; In N,N-dimethyl-formamide; at 140℃; under 22502.3 Torr; | Procedure b: A metal reactor was charged with 3-bromo-4-methyl-pyridine (200 g, 0.116 mol) and a mixture of DMF/MeOH (1 L/1L). To this was added Et3N (400 g, 0.395 mol), palladium (II) acetate (8 g, 0.036 mol) and 1 , l'-bis(diphenylphosphino)- ferrocene (16 g, 0.029 mol). The reactor was closed and pressurized with CO gas (3 MPa) and the reaction mixture was stirred and heated overnight at 140 C. The RM was cooled, filtered and concentrated in vacuo. The residue was purified by flash column chromatography over silica gel (gradient eluent: EtO Ac/Petroleum ether from 1/1 to 1/0). The product fractions were collected and the solvent was evaporated to afford the desired intermediate 1(90 g, 51%). |
51% | With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; triethylamine; In N,N-dimethyl-formamide; at 140℃; under 22502.3 Torr; | Procedure b: A metal reactor was charged with 3-bromo-4-methyl-pyridine (200 g, 0.1 16 mol) and a mixture of DMF/MeOH (1 L/1L). To this was added Et3N (400 g, 0.395 mol), palladium (II) acetate (8 g, 0.036 mol) and 1 , -bis(diphenylphosphino)ferrocene (16 g, 0.029 mol). The reactor was closed and pressurized with CO gas (3 MP a) and the reaction mixture was stirred and heated overnight at 140 C. The RM was cooled, filtered and concentrated in vacuo. The residue was purified by flash column chromatography over silica gel (gradient eluent: EtO Ac/Petroleum ether from 1/1 to 1/0). The product fractions were collected and the solvent was evaporated to afford the desired intermediate 1 (90 g, 51%). |
51% | With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; triethylamine; In N,N-dimethyl-formamide; at 140℃; under 22502.3 Torr; | A metal reactor was charged with 3-bromo-4-methyl-pyridine (200 g,0.116 mol) and a mixture of DMF/MeOH (1 L/1L). To this was added Et3N (400 g,0.395 mol), palladium (II) acetate (8 g, 0.036 mol) and 1,1?-bis(diphenylphosphino)ferrocene (16 g, 0.029 mol). The reactor was closed and pressurized with CO gas (3 MPa) and the reaction mixture was stirred and heated overnight at 140 C. The RM was cooled, filtered and concentrated in vacuo. The residue was purified by flash column chromatography over silica gel (gradient eluent:EtOAc/Petroleum ether from 1/1 to 1/0). The product fractions were collected and the solvent was evaporated to afford the desired intermediate 1 (90 g, 5 1%). |
51% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; palladium diacetate; triethylamine; In N,N-dimethyl-formamide; at 140℃; | Procedure b: A metal reactor was charged with 3-bromo-4-methyl-pyridine (200 g, 0.116 mol) and a mixture of DMF/MeOH (1 L/1L). To this Et3N (400 g, 0.395 mol), palladium (II) acetate (8 g, 0.036 mol) and 1 , -bis(diphenylphosphino)ferrocene (16 g, 0.029 mol) were added. The reactor was closed and pressurized with CO gas (3 MP a) and the reaction mixture was stirred and heated overnight at 140 C. The RM was cooled, filtered and concentrated in vacuo. The residue was purified by flash column chromatography over silica gel (gradient eluent: EtO Ac/Petroleum ether from 1/1 to 1/0). The product fractions were collected and the solvent was evaporated to afford the desired intermediate 21 (90 g, 51%). |
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