Structure of 1224157-88-3
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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. : | 1224157-88-3 |
Formula : | C12H14O4 |
M.W : | 222.24 |
SMILES Code : | O=C(OC(C)(C)C)C1=CC=C(O)C(C=O)=C1 |
MDL No. : | MFCD22370351 |
InChI Key : | LBSSNJFKFJEHIA-UHFFFAOYSA-N |
Pubchem ID : | 73553873 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 16 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.33 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 59.59 |
TPSA ? Topological Polar Surface Area: Calculated from |
63.6 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.04 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.73 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.16 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.58 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.18 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.94 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.32 |
Solubility | 1.06 mg/ml ; 0.00477 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.68 |
Solubility | 0.462 mg/ml ; 0.00208 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.68 |
Solubility | 0.466 mg/ml ; 0.0021 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 |
-6.43 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<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.81 |
* 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 |
---|---|---|
18%; 62% | With sodium periodate; In water; acetonitrile; at 20.0℃; for 48.0h; | To a stirred solution of the compound 5a (2.00 g, 8.93 mmol) and ethyl acrylate (7 mL, excess) in acetonitrile (10 mL) was added a solution of NaIO4 (6.00 g, 28.00 mmol) in water (20 mL) drop wise at 0 C and the reaction mixture was stirred at ambient temperature for 48 h. Acetonitrile was evaporated under reduced pressure, residue was diluted with water (30 mL) and extracted with ethyl acetate (3 × 50 mL). The organic extract was combined, washed with brine (50 mL) and dried over anhydrous Na2SO4. Solvent was removed under reduced pressure and product was chromatographed on silica gel.Elution with petroleum ether / ethyl acetate (85:15) first gave the minor aldehyde 8a as a colorless solid (0.183 g, 18%); mp 85 - 87 oC. [Rf = 0.5 petroleum ether/EtOAc (90:10)]. IR numax: 3390, 1663 cm-1. 1H NMR (400 MHz, CD3COCD3): delta 11.35 (s, 1H), 10.13 (s, 1H), 8.40 (d, J = 2.0 Hz, 1H), 8.14 (dd, J1 = 8.7 Hz, J2 = 2.0 Hz, 1H), 7.06 (d, J = 8.7 Hz, 1H), 1.59 (s, 9H). 13C NMR (100 MHz, CD3COCD3): delta 197.9, 165.3, 164.8, 138.2, 136.3, 125.0, 121.4, 118.2, 81.7, 28.3. HRMS (ESI): m/z [M + K]+ calcd for C12H14KO4: 261.0524; found: 261.0525. The above data is in agreement with those reported in literature[13]. Continued elution with petroleum ether/ethyl acetate (70:30) gave the desired adduct 9a as a colorless solid (1.77 g, 62%); mp 104 - 106 C. [Rf = 0.5 petroleum ether/EtOAc (70:30)]. IR max: 1732, 1712 cm-1. 1H NMR (400 MHz, CDCl3): delta 7.06 (dd, J1 = 6.4 Hz, J2 = 1.8 Hz, 1H), 4.15 (q, J = 7.1 Hz, 2H), 3.86 (dd, J1 = 6.4 Hz, J2 = 2.2 Hz, 1H), 3.21-3.15 (m, 2H), 3.11 (part of an AB system, JAB = 6.2 Hz, 1H), 2.93 (part of an AB system, JAB = 6.2 Hz, 1H), 2.44 (partly merged ddd, J1 = 13.3 Hz, J2 = 10.5 Hz, J3 = 2.6 Hz, 1H ), 2.02 (ddd, J1 = 13.3 Hz, J2 = 5.2 Hz, J3 = 2.9 Hz, 1H), 1.50 (s, 9H), 1.26 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3): delta 203.2, 172.1, 162.5, 140.4, 135.4, 81.9, 61.7, 57.3, 53.2, 51.2, 40.6, 37.8, 28.2, 25.8, 14.2. HRMS (ESI): m/z [M + Na]+ calcd for C17H22NaO6: 345.1309; found: 345.1306.Crystal data of 9a: Crystal data of compound 9a: C17H22O6, M = 322.36, triclinic, space group P-1 ( 2), a = 6.636 (4) A, b = 9.419 (6) A, c = 13.627 (8) A, = 92.616 (10), = 99.969(12), = 93.654(9), V = 835.8 (9) A3, Dc = 1.281 g/ cm3, Z = 2, F(000) = 344.00, Size: 0.45 x 0.20 x 0.09 mm3, Wavelength = 0.71070 A, GoF = 0.885, Absorption coefficient = 0.965 cm-1, Total/unique reflections = 8828 / 2929 [R(int) = 0.0950], T = 100 K, 2 range = 5.0 to 50.0, Final R [I > 2s(I)]: R1 = 0.0567, wR2 = 0.1604, R (all data): R1 = 0.0854, wR2 = 0.1604. Crystallographic data has been deposited with Cambridge Crystallographic data Centre, CCDC no. 1004667. Copy of the data can be obtained, free of charge, on application to CCDC. E-mail. Depositccdc.cam.ac.UK |
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