Structure of 393-53-3
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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. : | 393-53-3 |
Formula : | C6H4FNO2 |
M.W : | 141.10 |
SMILES Code : | C1=CN=CC(=C1C(=O)O)F |
MDL No. : | MFCD03789251 |
Boiling Point : | No data available |
InChI Key : | POLXLLIQWDBJMD-UHFFFAOYSA-N |
Pubchem ID : | 345361 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 31.15 |
TPSA ? Topological Polar Surface Area: Calculated from |
50.19 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.73 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.48 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.34 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.69 |
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 |
0.61 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.4 |
Solubility | 5.68 mg/ml ; 0.0403 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.1 |
Solubility | 11.1 mg/ml ; 0.0788 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.65 |
Solubility | 3.15 mg/ml ; 0.0223 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 |
-6.82 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 |
0.56 |
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) |
1.27 |
* 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 |
---|---|---|
24% | Example 117: 3-l(3-thienylmethyl)aminol-4-pyridinecarboxylic acid hydrochloride To a mixture of 3-fluoro-4-pyridinecarboxylic acid (200 mg, 1.417 mmol) and N-ethyl-N-(1-methylethyl)-2-propanamine (619 p1, 3.54 mmol) was added <strong>[27757-86-4](3-thienylmethyl)amine</strong> (198 mg, 1 .701mmol). The reaction mixture was heated using a microwave 160C for 4hr then diluted with DMSO (4ml) and purified by MDAP (High pH modifier, Method E) to give the free base compound as a whitesolid (83 mg). This was dissolved in 1 ,4-Dioxane (3 ml) then 2N HCI in ether (178 p1, 0.356 mmol)was added and the resulting solution concentrated under reduced pressure to give the title compoundas a yellow solid (92 mg, 24%)LCMS (Method B): Rt = 0.55 mins, MH+ = 235.1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | In 1,4-dioxane; water; at 140℃; for 14.0h; | 3-Fluoroisonicotinic acid (3.00 g, 21.3 mmol) was dissolved in dioxane (6 mL) and 30% aqueous methylamine solution (22.0 g, 213 mmol) was added. The reaction solution was heated to 140C and stirred for 14 hours. Conc. hydrochloric acid (12 N, 3 mL) was added and the pH was adjusted to 3, filtered and the filter cake was dried to give 3-(methylamino)isonicotinic acid (3.00 g, as a yellow solid) with a yield of 93%. 1H NMR: (400 MHz, DMSO-d6) delta 8.46(br, 1H), 7.89(s, 1H), 7.69(d, J = 5.2 Hz, 1H), 7.50(d, J = 5.2 Hz, 1H), 2.80(s, 3H). |
93% | In 1,4-dioxane; water; at 140℃; for 14.0h; | 3-Fluoroisonicotinic acid (3.00 g, 21.3 mmol) was dissolved in dioxane (6 mL), and then 30% methylamine aqueous solution (22.0 g, 213 mmol) was added. The reaction solution was heated to 140 C. and then stirred for 14 hours. Concentrated hydrochloric acid (12N, 3 mL) was added to adjust the pH value to pH=3, followed by filtration. The filter cake was dried to give 3-(methylamino)isonicotinic acid (3.00 g, yellow solid) with a yield of 93%. 1H NMR: (400 MHz, DMSO-d6) delta8.46 (s, 1H), 7.89 (s, 1H), 7.69 (d, J=4.8 Hz, 1H), 7.50 (d, J=4.8 Hz, 1H), 2.80 (s, 3H). |
42% | In 1,4-dioxane; water; at 125℃; for 9.5h;Microwave irradiation; | Example 153: 3-(methylamino)-4-pyridinecarboxylic acid Methylamine (0.321 mL,3.90 mmol, 40% solution in water) was added to a 3-fluoro-4- pyridinecarboxylic acid (250 mg, 1 .772 mmol) and 1 ,4-Dioxane (0.3 ml) and the mixture heated using a microwave to 125 C for 1.5 hr then 2 hr and finally an additional 6 hr. The mixture was allowed tocoolthen concentrated by evaporation. Water (10 ml) was added then the mixture acidifed to pH 3 using 37% HCI. The resulting bright yellow precipitate was filtered then washed with water (10 ml) to give the title compound as a yellow solid, 114 mg (42%).1H NMR (400 MHz, DMSO-S6) 8.2oppm (1H, 5), 7.84ppm (1H, d), 7.Ssppm (1H, d), 2.93ppm (3H, 5). |
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