Structure of 870281-86-0
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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. : | 870281-86-0 |
Formula : | C17H16FN3O |
M.W : | 297.33 |
SMILES Code : | O=C1N(C2=CC=CC=C2)C([C@@H](N)CC)=NC3=C1C(F)=CC=C3 |
MDL No. : | MFCD22124614 |
InChI Key : | BNMGOWXQUZHWIO-ZDUSSCGKSA-N |
Pubchem ID : | 59841052 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 22 |
Num. arom. heavy atoms | 16 |
Fraction Csp3 | 0.18 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 84.59 |
TPSA ? Topological Polar Surface Area: Calculated from |
60.91 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.71 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.55 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.03 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.18 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.14 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.92 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.63 |
Solubility | 0.0697 mg/ml ; 0.000234 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.48 |
Solubility | 0.0993 mg/ml ; 0.000334 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-5.68 |
Solubility | 0.000624 mg/ml ; 0.0000021 mol/l |
Class? Solubility class: Log S scale |
Moderately 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) |
Yes |
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 |
-6.3 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<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
3.34 |
* 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 |
---|---|---|
3.1 g | With triethylamine In <i>tert</i>-butyl alcohol at 30 - 85℃; for 24 h; | (S)-2-(1 -aminopropyl)-5-fluoro-3-phenylquinazolin-4(3H)-one prepared in example 26 (4.2 g) and t-Butanol (21 mL) were charged into a 100 mL round bottom flask. Triethylamine (3.91 mL) and 6-Chloropurine (2.5 g) were added at 30 00. The resultant reaction mixture was heated to85°C and stirred for 24 hours. The reaction mixture was evaporated completely under reduced pressure at 40°C. The resultant residue was diluted with water (100 mL) and stirred for 30 minutes. The precipitate was filtered and the solid was washed with water (30 mL) and n-Hexane (50 mL) and dried for 1 hour under vacuum. The crude was purified by chromatographyusing Si02 (1 00:200) (solvent MeOH: DCM: TEA:: 5: 94: 1). The eluted fractions were evaporated completely under vacuum. The isolated product was diluted in dichloromethane (100 mL) and the organic layer was washed with brine solution (2x25 mL). The organic layer dried over sodium sulphate (10 g) and evaporated under reduced pressure to yield 3.1 g of Idelalisib as pale yellow solid.Purity: 97.87percent by HPLC; chiral purity: 98.77percent by H PLC |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62.5 g | With N-ethyl-N,N-diisopropylamine In <i>tert</i>-butyl alcohol at 85 - 90℃; | Example 6:Preparation of 5-fluoro-3-phenyl-2-[(15)-l-(7H-purin-6-ylamino)propyl]- 4(3H)-quinazolinone [idelalisib] A mixture of 2-(l-aminopropyl)-5-fluoro-3-phenyl-3H-quinazolin-4-one (50 g, 0.17 mole) and 6-bromopurine (37.5 g, 0.18 mole) was taken in tert-butanol (500 mL). To this solution, 43.4 g DIPEA [Ν,Ν,-diisopropylethylamine] was added and the reaction mixture was stirred at 85 °C- 90 °C for 20 to 25 hours. After completion of the reaction, the reaction mixture was concentrated by distillation under vacuum and the residue was dissolved in methanol (500 mL). This solution was slowly added to water (5000 mL) and stirred for next 40 to 60 minutes. The solid was filtered then sucked dried. Finally, the solid was dried at 50 °C- 55 °C under vacuum for 4 to 5 hours to get 5-fluoro-3-phenyl-2-[(15)-l-(7H-purin-6-ylamino)propyl]-4(3H)- quinazolinone (idelalisib) (62.5 g, 89percent molar). |
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