Structure of 50735-34-7
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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. : | 50735-34-7 |
Formula : | C7H7BrN2O2 |
M.W : | 231.05 |
SMILES Code : | NC1=NC=C(C=C1C(=O)OC)Br |
MDL No. : | MFCD04117787 |
InChI Key : | POWKBBOOIZBIRZ-UHFFFAOYSA-N |
Pubchem ID : | 2763453 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 47.62 |
TPSA ? Topological Polar Surface Area: Calculated from |
65.21 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.6 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.6 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.22 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.91 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.17 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.3 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.52 |
Solubility | 0.7 mg/ml ; 0.00303 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.58 |
Solubility | 0.606 mg/ml ; 0.00262 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.6 |
Solubility | 0.578 mg/ml ; 0.0025 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) |
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 |
-6.57 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 |
0.0 |
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) |
1.76 |
* 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 |
---|---|---|
99% | With bromine; sodium hydrogencarbonate In dichloromethane at 0 - 20℃; for 1 h; | To a stirred solution of 2-amino-nicotinic acid methyl ester (2 g, 13.15 mmol) and sodium bicarbonate (2.2 g, 26.31 mmol) in DCM (30 mL) is added a solution of bromine (1.01 mL in DCM (20 mL) drop wise at 0° C. The reaction mixture is stirred at room temperature for 1 hour. The reaction mixture is quenched with sodium bisulfite solution (50 mL) and extracted with DCM (2*40 mL). The combined organic layers are washed with brine (40 mL), dried over sodium sulphate, filtered, and evaporated under reduced pressure to give the title compound as a yellow solid (3 g, 99percent). LCMS m/z (79Br/81Br) 231/233 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | at 80℃; for 18 h; Inert atmosphere | To a solution of 2-amino-5-bromonicotinic acid 22 (1.0 g, 4.6 mmol)in MeOH (10 mL) was added sulphuric acid (2.0 mL, 36.8 mmol)dropwise and the mixture was stirred at 80 °C for 18 h. After completionmonitored by TLC, the solvent was removed under reduced pressure.The residue was neutralised with sat. NaHCO3 (aq.) and extracted withethyl acetate (3×20 mL). The combined organic layers were driedover MgSO4 and concentrated in vacuo to afford the product 23 as awhite powder (1.0 g, 94percent) without further purification. m.p.148–149 °C; Rf (CH2Cl2/MeOH 20:1): 0.55; 1H NMR (400 MHz, d6-DMSO): δ 8.24 (1H, d, J=2.4 Hz), 8.21 (1H, d, J=2.4 Hz), 6.68–6.19(2H, br.s), 3.89 (3H, s); 13C NMR (100 MHz, d6-DMSO): δ 166.6, 158.0,154.4, 142.0, 107.5, 106.1, 52.4. HRMS (ESI+) Calc. for C7H7N2O2Br [M+H]+ 230.9764/232.9743, found 230.9765/232.9745. IR (neat,cm−1): v 3425, 3131, 2918, 1704, 1620, 1223, 796, 526. |
63% | Stage #1: for 0.25 h; Cooling with ice Stage #2: at 80℃; for 8 h; Inert atmosphere |
Compound 1 (27.40 g, 126.88 mmol) obtained in Step 1 of Example 1 was placed in a well-dried 1000 mL three-neck round bottom flask and placed in a water bath containing ice water. 250 mL of methanol was added and stirred for 15 minutes. Sulfuric acid (125.80 mL, 2360.00 mmol) was slowly added dropwise thereto. The mixture was stirred for 8 hours at a temperature of 80 ° C under a stream of nitrogen. The product was poured into 1500 mL of ice water and neutralized with NaHCO 3 until the pH reached 7. Extraction with dichloromethane followed by column separation with 100percent dichloromethane. The resulting solid was dried to give compound 2 (18.5 g, 63percent yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36% | at 75℃; for 48 h; | 2. To a suspension of 2-amino-5-bromonicotinic acid hydrobromide (18.8 g, 60.0 mmol) in 150 mL of methanol was added cone, sulfuric acid (6 mL). The mixture was heated at 75 °C for 2 days, evaporated, diluted with water (100 mL), basified with solid sodium bicarbonate to pH 7-8, and extracted with ethyl acetate (3 x 100 mL). The extracts were washed with brine (50 mL), dried over sodium sulfate and filtered. The filtrate was dried in vacuo and the residue was purified by flash chromatography eluted with ethyl acetate/hexanes (1/4) to afford methyl 2-amino-5- bromonicotinate as a white solid in 36percent yield (5.0 g). 1H NMR (400 MHz, CDC13): δ 8.26 (d, J= 2.8 Hz, 1H), 8.23 (d, J= 2.8 Hz, 1H), 3.92 (s, 3H). |
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