Structure of 719310-31-3
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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. : | 719310-31-3 |
Formula : | C13H16BrNO3 |
M.W : | 314.18 |
SMILES Code : | O=C(N1C2=CC(Br)=CC=C2OCC1)OC(C)(C)C |
MDL No. : | MFCD11865220 |
InChI Key : | JOFHRALTEXLLIC-UHFFFAOYSA-N |
Pubchem ID : | 56776935 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 18 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.46 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 76.6 |
TPSA ? Topological Polar Surface Area: Calculated from |
38.77 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.38 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.11 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.2 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.61 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.49 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.96 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.8 |
Solubility | 0.0503 mg/ml ; 0.00016 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.59 |
Solubility | 0.0803 mg/ml ; 0.000255 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.76 |
Solubility | 0.0547 mg/ml ; 0.000174 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) |
Yes |
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) |
Yes |
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 |
-6.01 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) |
3.02 |
* 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 |
---|---|---|
65% | With dmap; triethylamine; In tetrahydrofuran; at 20℃; | A mixture of the product 6-bromo-3,4-dihydro-2H-benzo[£][l,4]oxazine (1.37 g, 6.4 mmol), Boc20 (1.676 g, 7.68 mmol), Et3N (970 mg, 9.6 mmol), DMAP (78 mg, 0.64 mmol) in THF (27 mL) was stirred at room temperature overnight. The reaction mixture was diluted with water (200 mL) and extracted with ethyl acetate (100 mL). The organic layer was washed with water (50 mL) and brine, dried over Na2S04 and concentrated to give compound 0601-182 (1.3 g, 65%) as a yellow oil. LCMS: 258 [M-55]+. 1H NMR (400 MHz, OMSO-de) delta 1.49 (s, 9H), 3.78 (t, J= 4.8 Hz, 2H), 4.21 (t, J= 4.4 Hz, 2H), 6.83 (d, J = 4.4 Hz, 1H), 7.12 (dd, J; = 2.0 Hz, J2 = 8.4 Hz, 2H), 8.01 (s, 1H). |
65% | With dmap; triethylamine; In tetrahydrofuran; at 20℃; | A mixture of the product <strong>[105655-01-4]6-bromo-3,4-dihydro-2H-benzo[b][1,4]oxazine</strong> (1.37 g, 6.4 mmol), Boc2O (1.676 g, 7.68 mmol), Et3N (970 mg, 9.6 mmol), DMAP (78 mg, 0.64 mmol) in THF (27 mL) was stirred at room temperature overnight. The reaction mixture was diluted with water (200 mL) and extracted with ethyl acetate (100 mL). The organic layer was washed with water (50 mL) and brine, dried over Na2SO4 and concentrated to give compound 0601-182 (1.3 g, 65%) as a yellow oil. LCMS: 258 [M-55]+. 1H NMR (400 MHz, DMSO-d6) delta 1.49 (s, 9H), 3.78 (t, J=4.8 Hz, 2H), 4.21 (t, J=4.4 Hz, 2H), 6.83 (d, J=4.4 Hz, 1H), 7.12 (dd, J1=2.0 Hz, J2=8.4 Hz, 2H), 8.01 (s, 1H). |
65% | With dmap; triethylamine; In tetrahydrofuran; at 20℃; | The product 6-bromo-3,4-dihydro--2H- benzo [b] [1,4] oxazine (1.37g, 6.4mmol), Boc2O (1.676g, 7.68mmol), Et3N (970mg, 9.6mmol), DMAP (78mg, 0.64mmol) a mixture of in THF (27mL), and stirred at room temperature overnight. The reaction mixture was diluted with water (200 mL), and extracted with ethyl acetate (100 mL). The organic layer was washed with water (50 mL) and brine, dried and concentrated in Na2SO4, to give the compound 0601-182 as a yellow oil (1.3g, 65%). |
60% | With triethylamine;dmap; In tetrahydrofuran;Heating / reflux; | INTERMEDIATE 25; 6-Bromo-2,3-dihvdrobenzo[l,41oxazine-4-carboxylic acid fe/t-butyl ester; A mixture of Intermediate 13 (4.0 g, 18.6 mmol), di-fert-butyl dicarbonate (4.9 g, 22.4 mmol), 4-(dimethylamino)pyridine (50 mg, catalytic) and triethylamine (2.6 mL, 18.6 mmol) in THF (50 mL) was heated to reflux overnight. After cooling to r.t. the reaction mixture was concentrated in vacuo. The crude material was purified by column chromatography (SiO2, linear gradient elution: 0-100% EtOAc in heptane) to give the title compound as an off-white solid (3.5g, 60%). deltaH (DMSO-d6) 1.56 (9H, s), 3.80-3.89 (2H, m), 4.19-4.26 (2H, m), 6.77 (IH, d, J 8.9 Hz), 7.08 (IH, dd, J8.7, 2.4 Hz), 8.02 (IH, s). |
With dmap; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 15 - 25℃; for 48h;Inert atmosphere; | Step 1: To a solution of <strong>[105655-01-4]6-bromo-3,4-dihydro-2H-benzo[b][1,4]oxazine</strong> (12-a) (1.00 g, 4.67 mmol) in CH2Cl2 (30 mL) was added di-tert-butyl dicarbonate ((Boc)2O) (1.63 mL, 7.01 mmol), DIPEA (1.63 ml, 9.34 mmol) and DMAP (57 mg, 0.47 mmol) at rt. The resulting mixture was stirred at rt for 2 days under a nitrogen atmosphere. To the reaction mixture was added water (20 mL) and the mixture was stirred for 5 min. The organic layer was separated and the aqueous layer was extracted with CH2Cl2 (× 2). The combined organic extracts were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column using 0-100% EtOAc/hexanes to afford tert-butyl 6-bromo-2H-benzo[b][1,4]oxazine-4(3H)-carboxylate.1H NMR (400 MHz, CDCl3) G 8.01 (br s, 1H), 7.06 (dd, J = 8.8 Hz, J = 2.2 Hz, 1H), 6.74 (d, J = 8.8 Hz, 1H), 4.24-4.18 (m, 2H), 3.86-3.81 (m, 2H), 1.55 (s, 9H). |
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