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Type | HazMat fee for 500 gram (Estimated) |
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Structure of 5349-17-7
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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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Search for reports by entering the product batch number.
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Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
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CAS No. : | 5349-17-7 |
Formula : | C7H7Br2NO |
M.W : | 280.94 |
SMILES Code : | O=C(C1=CC=NC=C1)CBr.[H]Br |
MDL No. : | MFCD02681893 |
InChI Key : | RGALBQILADNMKA-UHFFFAOYSA-N |
Pubchem ID : | 2776239 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H302-H314 |
Precautionary Statements: | P260-P264-P270-P280-P301+P330+P331-P303+P361+P353-P304+P340-P305+P351+P338-P310-P363-P405-P501 |
Class: | 8 |
UN#: | 3261 |
Packing Group: | Ⅲ |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 52.34 |
TPSA ? Topological Polar Surface Area: Calculated from |
29.96 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.06 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.62 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.08 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.2 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.59 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.15 |
Solubility | 0.198 mg/ml ; 0.000706 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.32 |
Solubility | 1.35 mg/ml ; 0.00481 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.23 |
Solubility | 0.164 mg/ml ; 0.000582 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 |
-6.55 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) |
1.63 |
* 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 |
---|---|---|
With potassium tert-butylate; In 1,4-dioxane; for 16h; | t-BuOK (44 mg, 400 mumol) was added to a stirred solution of 4-mercaptomethyl piperidine-1-carboxylic acid tert-butyl ester (Preparation 1, 50 mg, 216 mumol) and 2-bromo-l- pyridin-4-ylethanone hydrobromide (121 mg, 432 mumol) in anhydrous dioxane (3 mL). After 16 h, the reaction mixture was diluted with EtOAc (70 mL), before being washed with H2O (15 mL) and brine (15 mL). After drying (MgSO4), the organic phase was filtered, concentrated, and purified by column chromatography (IH-EtOAc, 1 : 1) to furnish the title compound: RT = 3.72 min; mlz (ES+) = 351.2 [M+ H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | COMPOUND 3a4-(Pyridin-4-yl)thiazol-2-amine. Synthesis of batch 1. A mixture of 4-(bromoacetyl)pyridine hydrobromide (2) (2.21 g, 7.90 mmol), thiourea (0.60 g, 7.90 mmol) in anhydrous EtOH (10 ml) was stirred in a Biotage microwave at 100 C for 30 min. After colling to room temperature, the solid precipitate was filtered, dried under vacuum.Synthesis of batch 2. A mixture of 4-(bromoacetyl)pyridine hydrobromide (2) (2.54 g, 9.06 mmol), thiourea (0.69 g, 9.06 mmol) in anhydrous EtOH (10 ml) was stirred in a Biotage microwave at 100 C for 30 min. After colling to room temperature, the solid precipitate was filtered, dried under vacuum.Synthesis of batch 3. A mixture of 4-(bromoacetyl)pyridine hydrobromide (2) (2.16 g, 7.73 mmol), thiourea (0.58 g, 7.73 mmol) in anhydrous EtOH (10 ml) was stirred in a Biotage microwave at 100 C for 30 min. After colling to room temperature, the solid precipitate was filtered, dried under vacuum.Batches 1, 2, and 3 were combined, suspended in an aqueous sat. solution of NaHC03 , filtered, dried under vacuum to provide the title compound as a pale pink solid (5.53 g, 31.27 mmol, 95%), 1H NMR (400 MHz, CD3OD) delta 8.49 (d, J= 6.3 Hz, 2H), 7.79 (d, J= 6.3 Hz, 2H), 7.25 (s, 1H). | |
93% | A mixture of 2-bromo-l-pyridin-4-yl-ethanone hydrobromide (10 g, 35.59 mmol) and thiourea (2.71 g, 35.59 mmol) in absolute EtOH (100 mL) was re fluxed overnight. After cooling, the reaction mixture was diluted with water (400 mL), the pH was adjusted to 11 with ammonium hydroxide solution, and it was further stirred for 2h. The resulting precipitate was filtered, washed with water, and dried in vacuo to provide 5.85 g of 4-(2-amino- thiazol-4-yl)-pyridine as a pinkish solid (93% yield): 1H NMR (DMSO-dtf, ppm) delta 7.23 (broad s, 2H), 7.42 (s, 1H), 7.74 (d, 2H), 8.56 (d, 2H); [M+H]+ m/z 178 | |
Example 1-61N- [4-(4-Pyridinyl)- 1 ,3-thiazol-2-yl] benzamide (99). [0314] 4-(4-Pyridinyl)-l,3-thiazol-2-amine (98). A mixture of bromoketone hydrobromide 1 (5.0 g, 17.8 mmol) and thiourea (1.36 g, 17.8 mmol) in EtOH (100 mL) was stirred at reflux temperature for 2 h. The mixture was cooled to 20 0C, diluted with water (50 mL), the pH adjusted to ca. 8 with aqueous NH3 and the mixture stirred at 0 0C for 1 h. The precipitate was filtered, washed with water (5 mL) and ether (5 mL) and dried to give amine 98 (2.70 g, 86%) as a pink powder: mp (EtOH/H2O) 278-282 0C [lit. (Westphal, G. et al, J Prakt. Chemie (Leipzig) 1976, 318, 875) mp (EtOH) 276-277 0C]; 1H NMR delta 8.53 (dd, J= 4.6, 1.6 Hz, 2 H, H-2', H-6'), 7.91 (dd, J= 4.6, 1.6 Hz, 2 H, H-3', H-5'), 7.38 (s, 1 H, H-5), 7.16 (br s, 2 H, NH2); MS m/z 178.3 (MH+, 100%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | Example 1-82 7V-(2,6-Dimethylphenyl)-4-(4-pyridinyl)-l,3-thiazol-2-amine (137). [0347] 7V-(2,6-dimethylphenyl)-4-(4-pyridinyl)-l,3-thiazol-2-amine (137). A mixture of bromoketone hydrobromide 1 (0.30 g, 1.1 mmol) and iV-(2,6- difluorophenyl)thiourea (136) (0.20 g, 1.1 mmol) in EtOH (15 mL) was stirred at reflux temperature for 1 h. The mixture was cooled to 20 0C, diluted with water (50 mL), the pH adjusted to ca. 8 with aqueous NH3 and the mixture stirred at 0 0C for 1 h. The precipitate was filtered, washed with water (5 mL) and dried. The crude solid was purified by column chromatography, eluting with EtOAc, to give amine 137 (0.28 g, 91%) as a white powder: mp (EtO Ac/pet, ether) 208-210 0C; 1U NMR δ 9.34 (s, 1 H, NH), 8.55 (dd, J= 4.6, 1.6 Hz, 2 H, H-2', H-6'), 7.72 (dd, J = <n="153"/>4.6, 1.6 Hz, 2 H, H-3', H-5'), 7.46 (s, 1 H, H-5), 7.12-7.19 (m, 3 H, H-3", H-4", H-5"), 2.23 (s, 6 H, 2 x CH3); 13C NMR δ 168.5, 149.9 (2), 147.9, 141.4, 137.7, 135.7 (2), 128.4 (2), 127.0, 119.8 (2), 106.1, 17.8 (2); MS m/z 282.6 (MH+, 100%). Anal, calcd for Ci6Hi5N3S: C, 68.30; H, 5.37; N, 14.93. Found: C, 68.52; H, 5.47; N, 15.14%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | In neat (no solvent); for 0.0833333h;Microwave irradiation; Heating; | General procedure: Microwave method: Equimolar quantities of 4-(bromomethyl)pyridinehydrobromide (2 mmol) and substituted N-phenylthiourea (2mmol) are mixed and MW irradiated at 120 C with a power of 300 W foran optimal reaction time. After the reaction was completed, the crudemixture was cooled to 50 C before being suspended in water andalkalinized with NH4OH. To get the desired thiazole derivatives (3a-g),the precipitate was filtered and recrystallized from ethanol. |
60% | [0244] 7V-(4-Methoxyphenyl)-4-(4-pyridinyl)-l,3-thiazol-2-amine (27). A mixture of bromoketone hydrobromide 1 (1.26 g, 4.50 mmol) and 4- methoxyphenylthiourea (26) (0.82 g, 4.50 mmol) in EtOH (20 mL) was stirred at reflux temperature for 1 h. The mixture was cooled to 20 0C, diluted with water (50 mL), the pH adjusted to ca. 8 with aqueous NH3 and the mixture stirred at 5 0C for 2 h. The precipitate was filtered, washed with water (5 mL) and dried. The crude solid was purified by column chromatography, eluting with EtOAc, to give amine 27 (0.76 g, 60%) as a cream powder: mp (EtOAc) 178-180 0C; 1H NMR δ 10.13 (br s, 1 H, NH), 8.61 (dd, J= 4.5, 1.6 Hz, 2 H, H-2', H-6'), 7.83 (dd, J= 4.5, 1.6 Hz, 2 H, H-3', H-5'), 7.60 (m, 3 H, H-5, H-3", H-5"), 6.95 (ddd, J= 6.8, 3.5, 2.2 Hz, 2 H, H-2", H-6"), 3.74 (s, 3 H, OCH3); 13C NMR δ 164.1, 154.2, 150.0 (2), 147.6, 141.0, 134.4, 119.8 (2), 118.7 (2), 114.2 (2), 106.6, 55.1; MS m/z 284.5 (MH+, 100%). Anal, calcd for Ci5Hi3N3OS: C, 63.58; H, 4.62; N, 14.83. Found: C, 63.45; H, 4.65; N, 14.82%. |
A149148 [6221-13-2]
2-Bromo-1-(pyridin-4-yl)ethanone
Reason: Free-Salt