Structure of 367-30-6
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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. : | 367-30-6 |
Formula : | C6H5F2N |
M.W : | 129.11 |
SMILES Code : | C1=C(F)C=CC(=C1N)F |
MDL No. : | MFCD00007651 |
InChI Key : | YNOOQIUSYGWMSS-UHFFFAOYSA-N |
Pubchem ID : | 67775 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302+H312+H332-H317-H227 |
Precautionary Statements: | P264-P270-P271-P272-P280-P301+P312+P330-P302+P352+P312-P304+P340+P312-P333+P313-P370+P378-P403+P235-P501 |
Num. heavy atoms | 9 |
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 | 30.76 |
TPSA ? Topological Polar Surface Area: Calculated from |
26.02 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.47 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.54 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.4 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.34 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.99 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.95 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.1 |
Solubility | 1.02 mg/ml ; 0.00787 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.7 |
Solubility | 2.6 mg/ml ; 0.0202 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.56 |
Solubility | 0.357 mg/ml ; 0.00277 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 |
-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 |
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) |
1.0 |
* 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 |
---|---|---|
100% | In dichloromethane; at 20.0℃; | Example 1 Synthesis of N-(2,5-difluorophenyl)acetamide 11 To a solution of 2,5-difluoroaniline 10 (30.72 g, 238 mmol) in 100 ml of dichloromethane was added acetic anhydride (29.15 g, 285 mmol) at room temperature. The resulting mixture was stirred at room temperature overnight. The volatile solvent was evaporated, and water (200 ml) was added. A white solid was collected by filtration and dried in vacuum, giving the desired product 11 as a white solid, 40 g (100%). 1H NMR (300 MHZ, CDCl3) δ 8.16 (m, 1H), 7.42 (brs, 1H), 7.01 (m, 1H), 6.72 (m, 1H), 2.22 (s, 3H). |
92.8% | In dichloromethane; at 20.0℃; for 16.0h; | To a solution of compound 3.1 (10.0 g, 77.46 mmol, 1 equiv) in dichloromethane (35 mL) was added AC2O (9.47 g, 92.75 mmol, 8.69 mL, 1.20 equiv) in portions at 20 C. After addition was complete, the reaction mixture was stirred at 20 C for 16 hr. LC-MS showed compound 1 consumed, and the main product was compound 3.2 (r.t. = 0.626 min, [M+H]+ = 171.8). The reaction mixture was concentrated under reduced pressure. Then water (80 mL) was added to the residue and an off-white solid was collected by filtration and dried under vacuum to give compound 3.2 (12.3 g, 71.87 mmol, 92.8% yield). NMR (400 MHz, CDCb) d 8.23 - 8.12 (m, 1H), 7.46 (br s, 1H), 7.03 (dt, J = 4.8, 9.8 Hz, 1H), 6.72 (br t, J = 8.2 Hz, 1H), 2.24 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76.5% | In N,N-dimethyl-formamide; at 120℃; for 10h; | Step 1) Synthesis of 5-fluorobenzo [d] thiazole-2-thiol 2, 5-Difluoroaniline (1.00 g, 7.75 mmol) and potassium ethylxanthate (2.73 g, 17.05 mmol) were added into N, N-dimethylformamide (50 mL) in turn, the mixture was heated at 120 ? for 10 h. After the reaction is complete, the mixture was cooled to rt and diluted with water (100 mL) . The resulting mixture was adjusted with hydrochloric acid (1 M) to pH 4 to 5. Some solid precipitated, the mixture was filtered by suction. The solid was dried at 50 ? under a vacuum to give the title compound as a white solid (1.11 g, 76.5%) .MS (ESI, pos. ion) m/z: 185.00 [M+H] +; and1H NMR (DMSO-d6, 600 MHz) ? (ppm) : 13.98 (s, 1H) , 7.55 (d, J = 8.2 Hz, 1H) , 7.36~7.31 (m, 2H) . |
67% | In N,N-dimethyl-formamide; at 120℃; for 0.25h;microwave; | A mixture of 2,5-difluoro-phenylamine (129 mg, 1 mmol) and potassium o-ethyl dithiocarbonate (352 mg, 2.2 mmol) in DMF (5 mL) was heated to 120C for 15 min in microwave. The reaction mixture was cooled, diluted with 10 mL of ice water, and acidified with 3 mL of HCI solution (1 mol/L). Then the mixture was extracted with EtOAc (3 x 50 mL), washed with brine and dried over Na2SO/i. The dried organic layers were concentrated to give 5- fluorobenzo[d]thiazole-2-thiol (120 mg, 0.67 mmol, 67%). ESI-MS (M+l): 185 calc. for |
40% | In N,N-dimethyl-formamide; for 4h;Inert atmosphere; Heating; | General procedure: GP3-1: A solution of 2-halo substituted aniline (1.0 eq), potassium ethyl xanthate (1.2 eq or 2.2 eq,typically 2.2 eq) in 10 volume of anhydrous DMF was heated at 100 0Cor 120 0C for 4 hours under nitrogen. TLC monitored the progress ofreaction. After completion, the reaction mixture was cooled to room temperature,diluted with water (10 volume) and neutralized by 1 M HCl solution to pH 5. Theformed precipitate was collected by filtration, rinsed with water, firstlydried by rotavapor, and then dried by oil pump to afford 2-mercaptobenzothiazole.GP3-2: 2-mercaptobenzothiazole in 10 volume ofanhydrous DCM, was added by sulfuryl chloride (SO2Cl2, 1volume) under ice-cooled condition. The mixture was stirred at rt for 1 hour,which was monitored by TLC. After consumption of starting material, the mixturewas diluted by 30 volume of ether, following quenching carefully by addingwater. Stirring was kept for 1 hour to make sure the SO2Cl2was totally consumed and product was released. Organic layer was collected,neutralized by saturated NaHCO3, dried over Na2SO4and purified by silica gel chromatograph to give the pure product, which wasfinally characterized by LC-MS and NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With acetic anhydride; In benzene; | REFERENCE EXAMPLE 14 Preparation of 2,5-difluoro-4-nitroacetanilide STR43 20.5 g of 2,5-difluoroaniline was dissolved in 68 ml of benzene, and 17.8 g of acetic anhydride was dropwise added. Fifteen hours later, benzene was distilled off, and the residue was washed with ethyl ether to obtain 25.6 g of 2,5-difluoroacetanilide as white crystals. |
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