Structure of 1240480-36-7
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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. : | 1240480-36-7 |
Formula : | C8H11ClFNO |
M.W : | 191.63 |
SMILES Code : | FC1=CC([C@H](N)CO)=CC=C1.[H]Cl |
MDL No. : | MFCD12758113 |
InChI Key : | VJMNCZRJJLXISS-DDWIOCJRSA-N |
Pubchem ID : | 68088895 |
GHS Pictogram: |
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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 | 0.25 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 47.01 |
TPSA ? Topological Polar Surface Area: Calculated from |
46.25 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
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 |
1.68 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.4 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.16 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.92 |
Solubility | 2.33 mg/ml ; 0.0122 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.59 |
Solubility | 4.91 mg/ml ; 0.0256 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.18 |
Solubility | 1.26 mg/ml ; 0.00659 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 |
-6.74 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) |
1.76 |
* 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 |
---|---|---|
Boc-protected amino alcohol (A)A mixture of the amino alcohol hydrochloride (192.22 mmol) and di-f-butyl dicarbonate (262.63 mmol, 1.37 eq) was suspended in f-BuOH (250 mL, 6.25 volumes) and then treated with aqueous 2 N NaOH (120 mL, 240 mmol). The contents were warmed to 75 C (immediate effervescence was observed) for 4 h. The internal temp was then reduced to 50 C, and the contents were added to water (2 L) with vigorous stirring. After 15 min, a pure, white solid (A) precipitated, and the contents were cooled to 5 C, prior to filtration. The collected solid was washed with water (0.5 L) and dried under vacuum at 35 C for 18 h (90-99% yield).Example 1 was prepared following the general synthesis of A-E starting with (S)-2- amino-2-(3-fluoro-phenyl)-ethanol. LC-MS [366 (M+1 )] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | With hydrogenchloride; In methanol; at 20.0℃; for 1.0h; | General procedure: Step 4 To a solution of 60 (3.0 g, 8.0 mmol) in MeOH (100 mL) was added 3N HCl/MeOH (8.0 mL, 24 mmol). After stirring at RT for 1 h, the mixture was concentrated in vacuo and diluted with EtOAc (30 mL). The solid was filtered and washed with EtOAc (20 mL) to afford 880 mg (57%) of 62a as a white solid. 1H NMR (500 MHz, CD3OD) δ 7.50 (m, 1H), 7.32-7.28 (m, 2H), 7.19 (m, 1H), 7.41 (m, 1H), 3.93 (m, 1H), 3.82 (m, 1H). LCMS (ESI) m/z: 156.1 [M+11]+. |
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