Structure of 88982-82-5
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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. : | 88982-82-5 |
Formula : | C4H2BrNO2S |
M.W : | 208.03 |
SMILES Code : | O=C(C1=NC(Br)=CS1)O |
MDL No. : | MFCD09701413 |
InChI Key : | AYUAEJPYEJEHJN-UHFFFAOYSA-N |
Pubchem ID : | 15122065 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 36.77 |
TPSA ? Topological Polar Surface Area: Calculated from |
78.43 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.12 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.84 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.6 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.1 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.27 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.39 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.63 |
Solubility | 0.483 mg/ml ; 0.00232 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.11 |
Solubility | 0.162 mg/ml ; 0.000781 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.53 |
Solubility | 6.2 mg/ml ; 0.0298 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 |
No |
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 |
-6.26 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 |
0.56 |
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) |
2.52 |
* 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 |
---|---|---|
To a suspension of 4-bromothiazole-2-carboxylic acid (CAS 88982-82-5) (0.1 12 g, 0.538 mmol) in DCM (5.38 mL) and DMF (8.34 mu, 0.108 mmol) was added oxalyl chloride (0.059 mL, 0.67 mmol) and this was stirred at room temperature. After 30 minutes the reaction was concentrated. The solid was dissolved in DCM (5.38 mL), and methyl 2-(2- aminophenyl)acetate hydrochloride (CAS 35613-44-6) (0.089 g, 0.538 mmol) and DIPEA (0.188 mL, 1 .077 mmol) were added and the reaction was stirred at room temperature. After 5 minutes the reaction was partially concentrated and then purified directly by flash chromatography (0-50% EtOAc: Heptanes) to provide the title compound. MS (ESI-) m/z 353.1 , 355.1 (M-H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | To asolution of isobutyl chloroformate (10.0 µL, 0.08 mmol) in THF (4.0 mL) at -40 C, a mixture of 4-bromo-1,3-thiazole 2-carboxylic acid 11(16.0 mg, 0.08 mmol) and N-methylmorpholine(17.0 µL, 0.15 mmol) in THF (1.00 mL) was added slowly. The resulting mixture was stirred at - 5 C for 30 minutes and a solution of 2-amino 6-bromopyridine (65.0 mg, 0.58 mmol) in THF (2.00 mL) was added. This solution was vigorously stirred at room temperature overnight and then concentrated under reduced pressure, extracted with water/ethyl acetate. Thecombined organic fractions was dried over Na2SO4, concentrated under reduced pressure and purified by column chromatography on silica gel (hexane/ethyl acetate = 10:1) to afford 4-bromo-N-(6-fluoropyridin-2-yl)thiazole-2-carboxamide6bg (10.0 mg, 43%) as a white solid:1H-NMR (400MHz, CDCl3) δ 9.48(s, 1H), 8.17-8.15 (d, J = 8 Hz, 1H),7.89-7.83 (dd, J = 16, 8 Hz, 1H),7.571-7.569 (d, J = 0.8 Hz, 1H)6.75-6.73 (dd, J = 8, 1.6 Hz, 1H).13C-NMR (100 MHz, CDCl3) δ 162.7, 160.9, 156.4, 148.6, 143.44, 143.37,126.3, 124.4, 110.66, 110.62, 105.55, 105.20. LC/MS (ESI-) 299.9 (M-H)+. | |
43% | To 4.0 mL of tetrahydrofuran (THF) is added isobutyl chloroformate (10.0 [mu] L, 0.08 mmol) were added and cooled to -40 [deg.] C.To 1.0 mL of tetrahydrofuran (THF) was added 4-bromothiazole-2-carboxylic acid(16.0 mg, 0.08 mmol) and N-methylmorpholine (17.0 [mu] L, 0.15 mmol)Was slowly added dropwise to the reaction solution, followed by stirring at -5 DEG C for 30 minutes.To 2.0 mL of tetrahydrofuran (THF) was added2-Amino-6-fluoropyridine (65.0 mg, 0.58 mmol)Was added, and the mixture was stirred at room temperature for 12 hours. After completion of the reaction, water was added, and the mixture was extracted with ethyl acetate, and the organic layer was separated by distillation under reduced pressure. The organic layer was dried over anhydrous Na2SO4 and purified by column chromatography to obtain 10.0 mg(Yield: 43%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,2-dimethoxyethane; water; at 100℃; for 24h;Inert atmosphere; | General procedure: 4-Bromothiazole-2-carboxylic acid (compound 1, 1 eq) and boronic acid derivatives (compound 2a-g, 1.5 eq) were suspended in dimethoxy ethane (DME)/H2O (16 volume, 3:1). Then, Pd(PPh3)4 (0.05 eq) and K2CO3 (1.5 eq) were added to the suspension. The obtained mixture was heated to about 100 C and stirred for about 24 h under nitrogen atmosphere. The solution was cooled to room temperature and acidified with concentrated hydrochloric acid. Then, the precipitate was filtered and washed with water. The obtained wet cake was redissolved in dichloromethane. The organic phase was washed with saturated sodium bicarbonate (NaHCO3) aqueous solution for 30 min. Then, the aqueous phase was acidified again with concentrated hydrochloric acid, and the precipitate was filtered to obtained compounds 3a-g. |
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