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Structure of 1211580-54-9
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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. : | 1211580-54-9 |
Formula : | C6H4BrF2N |
M.W : | 208.00 |
SMILES Code : | FC(C1=NC=CC(Br)=C1)F |
MDL No. : | MFCD18257229 |
InChI Key : | MNMLGZMORMDPJI-UHFFFAOYSA-N |
Pubchem ID : | 58579539 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H302-H314 |
Precautionary Statements: | P501-P260-P270-P264-P280-P303+P361+P353-P301+P330+P331-P363-P301+P312+P330-P304+P340+P310-P305+P351+P338+P310-P405 |
Class: | 8 |
UN#: | 1759 |
Packing Group: | Ⅱ |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.17 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 37.0 |
TPSA ? Topological Polar Surface Area: Calculated from |
12.89 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.65 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.2 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.3 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.18 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.9 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.44 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.89 |
Solubility | 0.266 mg/ml ; 0.00128 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.1 |
Solubility | 1.63 mg/ml ; 0.00786 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.49 |
Solubility | 0.0673 mg/ml ; 0.000324 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 |
-6.01 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 |
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) |
1.59 |
* 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% | With diethylamino-sulfur trifluoride; at 20℃; for 16h; | [0207] Step 1: 4-Bromo-2-(difluoromethyl)pyridine : To a 4- bromopicolinaldehyde (5.0 g, 26.88 mmol) was added diethylaminosulfur trifluoride (7.03 mL, 53.7 mmol), and the mixture was stirred at rt for 16 h. The reaction was quenched with aq. sodium bicarbonate solution (50 mL) and extracted with ethyl acetate (3 X 100 mL). The combined organic layers were washed with brine (2 X 50 mL), dried over sodium sulfate, filtered, concentrated and purified by column chromatography (100- 200 silica) using 5% ethyl acetate in hexane as eluent to afford 4-bromo-2- (difluoromethyl)pyridine (3.0 g, 14.492 mmol, 54% yield ). lH NMR (400 MHz, CDC13) delta = 8.48 (d, J = 4.9 Hz, 1H), 7.82 (d, J = 1.5 Hz, 1H), 7.66-7.50 (m, 1H), 6.60 (t, 1H). LCMS: 207.9 [M+H]+. |
49.7% | With diethylamino-sulfur trifluoride; In chloroform; at 0 - 20℃; for 12h; | DAST (0.620 mL, 4.69 mmol) was added dropwise to a solution of <strong>[131747-63-2]4-bromopicolinaldehyde</strong> (700 mg, 3.76 mmol) in Chloroform (21 mL) at 0 C. The reaction mixture was stirred at 20 C. for 12 h. The reaction mixture was poured in to saturated NaHCO3 solution (20 mL), and was extracted with DCM (2×20 mL). The DCM layer was dried over anhydrous Na2SO4, filtered and filtrate was evaporated to afford 4-bromo-2-(difluoromethyl)pyridine (400 mg, 1.870 mmol, 49.7% yield) as light yellow solid, LCMS (m/z) 208.0 [M+H]+. |
49.7% | With N,N-diethyltrifluoromethanesulfenamide; In chloroform; at 0 - 20℃; for 12h; | DAST (0.620 mL, 4.69 mmol) was added dropwise to a solution of 4- bromopicolinaldehyde (700 mg, 3.76 mmol) in Chloroform (21 mL) at 0 C. The reaction mixture was stirred at 20 C for 12h. The reaction mixture was poured in to saturated NaHC03 solution (20 mL), and was extracted with DCM (IX 20 mL). The DCM layer was dried over anhydrous Na2S04, filtered and filtrate was evaporated to afford 4-bromo- 2-(difluoromethyl)pyridine (400 mg, 1.870 mmol, 49.7 % yield) as light yellow solid, LCMS (m/z) 208.0 [M+H]+. |
32% | With diethylamino-sulfur trifluoride; In chloroform; at 0 - 20℃;Inert atmosphere; | Example 30i 4-Bromo-2-(difluoromethyl)pyridine Diethylaminosulphur trifluoride (4.08 mL, 33.31 mmol) was added to <strong>[131747-63-2]4-bromopicolinaldehyde</strong> (0.267 M in chloroform) (100 mL, 26.7 mmol) at 0 C. under an atmosphere of argon. The reaction mixture was stirred over night while the temperature was raised to room temperature. The reaction was quenched by addition of aqueous sodium bicarbonate (sat.) and was further diluted with dichloromethane. The solids were filtered off through a pad of Celite. The organic layer was collected and the water phase was extracted with dichloromethane (*3). The organic layers were pooled, dried (Na2SO4), filtered and concentrated. Purification by silica chromatography using 0 to 60% diethyl ether in pentane gave the title compound (1.78 g, 32%). 1H NMR (400 MHz, DMSO-d6) delta ppm 8.59 (d, 1H) 7.98 (d, 1H) 7.90 (dt, 1H) 6.98 (t, 1 H); MS (APCI+) m/z 208, 210 [M+H]+. |
32% | With diethylamino-sulfur trifluoride; In chloroform; at 0 - 20℃;Inert atmosphere; | To a solution of <strong>[131747-63-2]4-bromopicolinaldehyde</strong> (10 g, 53.76 mmol) in CHCI3 (200.0 mL) was added diethylaminosulfur trifluoride (8.5 mL, 64.51 mmol) at 0C under argon. The reaction mixture was stirred overnight while the temperature was raised to room temperature. The reaction was quenched by addition of aqueous NaHC03 and further diluted with CH2CI2. The solids were filtered off through a pad of celite. The organic layer was separated and aqueous phase was extracted with CH2CI2 (3x). The organic phase dried over Na2S04. The suspension was concentrated to dryness and the resulting crude product was purified by Teledyne-Isco flash system by using Hexane/EtOAc, 0 to 20% of ethyl acetate in hexane to provide compound 16 as light yellow liquid (3.5 g, 32% yield). lH NMR (400 MHz, DMSO-d6) delta (ppm): 8.79 (d, 1H), 7.98 (s, 1H), 7.80 (d, 1H), 4.86 (s, 1H). |
800 mg | With diethylamino-sulfur trifluoride; In dichloromethane; at 0 - 20℃;Inert atmosphere; | Description 1284-Bromo-2-(difluoromethyl)pyridine (D128)To a solution of <strong>[131747-63-2]4-bromopicolinaldehyde</strong> (1 g) in DCM (20 mL) stirred under nitrogen atmosphere at 0C was added DAST (1.065 mL). The reaction mixture was stirred at RT overnight. To the mixture was added water, and then extracted with DCM (3 x50 mL). The organic phase was washed with saturated NaHCO3, water, and brine, then dried over MgSO4 and filtered to give the titlecompound (800 mg) as yellow oil. MS (ESI): C6H4BrF2N requires 207; found no mass. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55.90% | With potassium carbonate; In N,N-dimethyl-formamide; at 90℃; for 1h;Inert atmosphere; | General procedure: To a solution of 1Himidazole4carbaldehyde (0.50 g, 5.20 mmol) and 6chloro4methoxynicotinonitrile (1.05 g, 6.24 mmol) in DMF (10 mL) was added K2CO3 (1.08 g, 7.81 mmol) at ambient temperature under a nitrogen atmosphere. The resulting reaction mixture was heated at 90°C for 1 h. The reaction mixture was cooled to ambient temperature and diluted with ice water (30 mL). The resulting precipitate was filtered and was washed with ethanol (2 mL) to obtained Intermediate 11 (0.30 g, 25.00percent).1H NMR (400 MHz, DMSOd6) G ppm 4.13 (s, 3 H), 7.81 (s, 1 H), 8.83 (s, 2 H), 8.95 (d, J = 1.19 Hz, 1 H), 9.87 (s, 1 H). LCMS (MethodL): retention time 0.75 min, [M+H] 229.1. |
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