Structure of 1441723-24-5
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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. : | 1441723-24-5 |
Formula : | C8H7FN2O |
M.W : | 166.15 |
SMILES Code : | N#CC1=CC(OC)=C(N)C=C1F |
MDL No. : | MFCD26407017 |
InChI Key : | PJOVJLSGRCXXOL-UHFFFAOYSA-N |
Pubchem ID : | 71743885 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 42.01 |
TPSA ? Topological Polar Surface Area: Calculated from |
59.04 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.56 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.03 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.72 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.94 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.5 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.35 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.82 |
Solubility | 2.5 mg/ml ; 0.015 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.86 |
Solubility | 2.29 mg/ml ; 0.0138 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.52 |
Solubility | 0.498 mg/ml ; 0.003 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 |
-6.58 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 |
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) |
1.62 |
* 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 |
---|---|---|
With trifluoroacetic acid; In butan-1-ol; at 75.0℃; for 2.0h;Sealed tube; | Example 3: 2-Fluoro-5-methoxy-4-(4-(methylamino)-5- (trifLuoromethyl)pyrimidin-2-ylamino)benzonitrile To a mixture of <strong>[1441723-24-5]4-amino-2-fluoro-5-methoxybenzonitrile</strong> (66 mg, 0.40 mmol) and 2-chloro-N-methyl-5-(trifluoromethyl)pyrimidin-4-amine (0.10 g, 0.47 mmol) in 1- butanol (2 mL) was added TFA (0.05 mL, 0.07 mmol). The reaction was stirred in a sealed tube at 75 C for 2 h. The reaction was concentrated and the product was isolated by reverse-phase HPLC to give 2-fluoro-5-methoxy-4-(4-(methylamino)-5- (trifluoromethyl)pyrimidin-2-ylamino)benzonitrile. 1H NMR (400 MHz, DMSO) ? 8.57 (d, J = 13.4, 2H), 8.34 (s, 1H), 8.29 (d, J = 6.1, 1H), 7.56 - 7.42 (m, 3H), 3.93 (s, 3H), 2.95 (s, 3H); LRRK2 Ki = 0.022. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With tris-(dibenzylideneacetone)dipalladium(0); DavePhos; In N,N-dimethyl-formamide; at 100.0℃; for 6.0h; | Step 3: 4-Amino-2-fluoro-5-methoxybenzonitrile To a pressure tube was added 4-bromo-5-fluoro-2-methoxyaniline (0.24 g, 1.1 mmol), zinc cyanide (0.10 g, 0.87 mmol), Pd2(dba)3 (100 mg, 0.11 mmol), DavePhos (86 mg, 0.22 mmol) and DMF (3 mL). The reaction was sealed and stirred at 100 C for 6 hours. The reaction was diluted with water and extracted with EtOAc. The combined organic extracts were washed with brine, dried over sodium sulfate, filtered and concentrated. The crude product was purified by flash chromatography to give 4-amino- 2-fluoro-5-methoxybenzonitrile (0.18 g, 77%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine; at 480.0℃; for 4.0h;Inert atmosphere; Sealed tube; | General procedure: In a sealed vial, i-(benzenesulfonyl)-6-chloro-indole-3-sulfonyl chloride XII-19 (i92 mg, 0.49 mmol) was dissolved in pyridine (4 mL) under argon. 2,i,3-benzoxadiazol-5-amine(i35 mg, i mmol) was added and stirred at room temperature overnight. The reaction mixture was evaporated to dryness then the residue was taken into DCM. The organic phase was washed with HCI i N and brine, dried over Mg504 and evaporated. The dark oil residue solidified on standing and was then triturated in ACN/water (8/2), sonicated and filtered, washed with water and dried under vacuum to provide i70 mg of ii(benzenesulfonyl)-N-(2,i ,3-benzoxadiazol-5-yl)-6-chloro-indole-3-sulfonamide 1-201 a as a yellow solid.Yield: 7i%.Basic LCMS Method i (ES-): 487 (M-H)-, iOO % purity.1H NMR (400 MHz, DMSO-d6)oe ii.52(s, iH), 8.99(s, iH), 8.i6-8.iO (m, 2H), 7.98(d, J= i .8 Hz, i H), 7.9i (dd, J = 9.i, 3.2 Hz, 2H), 7.63 (t, J = 7.5 Hz, i H), 7.56 - 7.5i (m, 2H),7.43 - 7.36 (m, 2H), 7.25 (dd, J = 9.6, i .9 Hz, i H). |
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