Structure of 630384-36-0
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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. : | 630384-36-0 |
Formula : | C11H11IO2 |
M.W : | 302.11 |
SMILES Code : | O=C(C1(C2=CC=C(I)C=C2)CC1)OC |
MDL No. : | MFCD15523646 |
InChI Key : | AFNUSZPFMBSKAE-UHFFFAOYSA-N |
Pubchem ID : | 58841088 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H319 |
Precautionary Statements: | P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.36 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 62.41 |
TPSA ? Topological Polar Surface Area: Calculated from |
26.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.79 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.71 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.43 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.01 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.68 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.92 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.54 |
Solubility | 0.0872 mg/ml ; 0.000289 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.92 |
Solubility | 0.367 mg/ml ; 0.00121 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.23 |
Solubility | 0.0178 mg/ml ; 0.0000589 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) |
Yes |
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 |
-6.22 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 |
1.0 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) |
1.95 |
* 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 |
---|---|---|
73.9% | In tetrahydrofuran; at -78 - 0℃; for 1.0h; | Part A.1- (4-Iodo-phenyl)-cyclopropanecarboxylic acid methyl ester (0.96 g, 3.17 mmol) was stirred in THF (15 mL)at-78 C underN2. MeMgCl (3.0M in THF, 4.2 mL, 4.0 eq) was added dropwise, and the reaction was stirred for 1 h during which period the temperature was raisedfrom-78 C to0 C. It was quenched by the addition of sat'dNH4Cl, and extracted with EtOAc (2 x). The organics were washed withH20 and brine, dried overMgSO4, filtered, and concentrated to dryness. The residue was purified by FCC (silica gel, hexanes, then hexanes:CH2Cl2=1 :1 to 0: 1) to give 2- [l- (4-iodo-phenyl)-cyclopropyl]-propan-2-ol (0.71 g, <Desc/Clms Page number 396>yield: 73.9%). LC/MS(ESI+) 303.4 (M+H) +,tR=2. 57 min (10- 90% CH3CN/H2O in a 4-min run). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With water; potassium carbonate;palladium diacetate; In DMF (N,N-dimethyl-formamide); at 20℃; under 760.051 Torr; | Part A. 4-Iodophenylcyclopropyl acid, methyl ester (1.40 g, 4.63 mmol) was dissolved in DMF/H2O (1:2, v/v, 5 mL total) and K2CO3 (1.28 g, 9.26 mmol, 2 eq) and was added to a slurry of Pd(OAc)2 (2.08 g, 9.26 mmol, 2 eq) under CO atmosphere (1 atm). After overnight at rt, the mixture was quenched by diluting with EtOAc and H2O. The organic layer was washed with H2O (2*). The combined aqueous layers were acidified with conc. HCl, extracted with CH2Cl2 (3*), dried over MgSO4, filtered, and concentrated under vacuum overnight to give 4-(1-methoxycarbonyl-cyclopropyl)-benzoic acid (0.987 g, yield: 97%). 1H NMR (acetone-d6) delta 7.95 (d, J=8.1 Hz, 2H), 7.46 (d, J=8.1 Hz, 2H), 3.55 (s, 3H), 1.55 (m, 2H), 1.22 (m, 2H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With chloro-trimethyl-silane; at 0 - 20℃; | To a solution of compound LII-3 (0.86 g, 3 mmol) in methanol (15 mL) was added dropwise chloro-trimethyl-silane (0.33g, 3 mmol) at 0 C. After addition, the mixture was stirred overnight at room temperature and then the solvent was evaporated under vacuum to yield compound LII-4 (0.9 g, yield 100%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In N,N-dimethyl-formamide; at 20℃;Inert atmosphere; | To a mixture of compound LII-4 (0.604 g, 2 mmol) and compound LII-6 (0.4 g, 4 mmol) in DMF (10 mL) and TEA (2 mL) was added Cul (0.04 g, 0.2 mmol) and Pd(PPh3)2Cl2 (0.14 g, 0.2 mmol). The mixture was purged with nitrogen for 5 minutes and stirred under N2 at room temperature overnight. The mixture was diluted with water (20 mL) and extracted with EtOAc (30 mL x 3). The combined organic layers were washed with brine, dried over Na2S04, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (PE: EA = 20: 1) to afford compound LII-7 (0.48 g, yield: 88%). |
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