Structure of 51376-06-8
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CAS No. : | 51376-06-8 |
Formula : | C6H3BrN2O |
M.W : | 199.00 |
SMILES Code : | BrC2=CC1=NON=C1C=C2 |
MDL No. : | MFCD02682026 |
InChI Key : | ZWDFFESFCIACQC-UHFFFAOYSA-N |
Pubchem ID : | 2776298 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 39.5 |
TPSA ? Topological Polar Surface Area: Calculated from |
38.92 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.11 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.87 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.99 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.76 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.15 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.97 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.92 |
Solubility | 0.24 mg/ml ; 0.00121 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.31 |
Solubility | 0.977 mg/ml ; 0.00491 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.4 |
Solubility | 0.0794 mg/ml ; 0.000399 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) |
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 |
-6.19 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 |
0.55 |
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<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.46 |
* 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 caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In N,N-dimethyl-formamide; at 100℃; for 17h; | 5-bromo-2,1,3-benzoxadiazol (0.56 g), cesium carbonate (1.1 g), 2,2'- bis(diphenylphosphino)-1,r-binapthyl(0.14 g) and Tris -(dibenzylideneacetone) dipalladium(O) (0.1 g) were added to a solution of (5R)-3-(3-fluoro-4-piperazin-1- ylphenyl)-5-(lH-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-2-one(0.98 g) (obtained from Step b) in dry dimethylformamide (15 mL) and the reaction mixture was heated at 100 C for about 17 hours. The reaction mixture was filtered, the solvent was removed by evaporation and the crude product thus obtained was purified by column chromatography using 2 % methanol in dichloromethane to yield the title product (0.17 g).Melting point: 153-173 C; EIMS (m/z): 465.17; 1HNMR(DMSO): delta 8.17 (s, 1H), 7.90-7.87 (d, 1H), 7.74 (t, 2H), 7.44 (dd, 1H), 7.13 (m, 2H), 6.89 (s, 1H), 5.15-5.10 (m, 1H), 4.83 (d, 2H), 4.21 (t, 1H), 3.89-3.84 (t, 1H), 3.48 (m, 4H), 3.14 (m, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With triphenylphosphine; In toluene; at 110℃; for 4h; | Triphenylphosphine (1.1 mmol) was dissolved in dry toluene (3 mL) and stirred at 110C under argon atmosphere; then, 6-bromobenzo[c][1,2,5]oxadiazole 1-oxide (1 mmol) in toluene (0.5 mL) was added dropwise over 1 hour and the resulting mixture was stirred for 3 hours [4]. After completion, the solvent was evaporated in vacuo, and the crude was purified through flash column chromatography (cyclohexane - diethyl ether 98:2), to afford the desired product as a pale pink solid. Yield: 60%. TLC (cyclohexane - diethyl ether 98:2): Rf = 0.5. Mp: 74C. 1H-NMR (300 MHz, DMSO) 8.49 (s, 1H, H4), 8.04 (d, J = 9.4 Hz, 1H, H7), 7.69 (dd, J = 9.4, 1.6 Hz, 1H, H6). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In N,N-dimethyl-formamide; at 100℃; for 17h; | Cesium carbonate (0.23 g), 2,2'-bis(diphenylphosphino)-1,1'-binapthyl (0.06 g), 5- bromo-2,1,3-benzoxadiazol (0.12 g) and Tris -(dibenzylideneacetone) dipalladium(O) (0.1 EPO <DP n="55"/>g) were added to a solution of N-[(5S)-3-(3,5-difluoro-4-piperazin-1-ylphenyl)-2-oxo- l,3-oxazolidin-5-yl]methyl}acetamide (0.21 g) (which can be prepared according to Example 32(i) in U.S. Patent No. 5,547,950 at page 25) in dry dimethyl formamide (10 mL) and the reaction mixture was heated at 100 C for 17 hours. The reaction mixture was filtered and the solvent was evaporated. The crude product thus obtained was purified by column chromatography using 2 % methanol in dichloromethane as eluent to yield the title compound (0.025 g).Melting point: 207-213 C; EMS (m/z): 388;1HNMR(CDCl3): delta 7.91 (m, 2H), 7.62 (m, 2H), 7.52 (t, 1H), 7.35 (dd, 1H), 6.10 (t, 1H), 4.84 (m, 1H), 4.12 (t, 1H), 3.87 (t, 1H), 3.71 (m,2H), 2.02 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In N,N-dimethyl-formamide; at 100℃; for 17h; | Cesium carbonate (0.46 g), <strong>[51376-06-8]5-bromo-2,1,3-benzoxadiazole</strong> (0.23 g), 2,2'- bis(diphenylphosphino)-1,1'-binapthyl (0.074 g) and tris-(dibenzylideneacetone) dipalladium(O) (0.054 g) were added to a solution of N-[(5S)-3-(3-fluoro-4-piperazin-1- ylphenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide (0.4 g) (which can be prepared according to Example l(k) in WO 93/23384, at page 14) in dry dimethyl formamide (15 mL) and the reaction mixture was heated at 100 C for 17 hours. The reaction mixture was filtered and the solvent was evaporated. The crude product thus obtained was purified by column chromatography using 2 % methanol in dichloromethane and sonicated in ether to yield the title compound (0.12 g).Melting point: 201-222 C; EIMS (m/z): 455;1HNMR(CDCl3): delta 7.71 (d, 1H), 7.48 (dd, 1H), 7.33 (dd, 1H), 7.12 (dd, 1H), 6.98 (t, 1H), 6.79 (s, 1H), 5.99 (t, 1H), 4.76 (m, 1H), 4.02 (t, 1H), 3.85-3.55 (m, 3H), 3.47 (m, 4H), 3.24 (m, 4H), 2.03 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine;bis-triphenylphosphine-palladium(II) chloride; In N,N-dimethyl-formamide; at 100℃; for 3h; | <strong>[51376-06-8]5-bromo-2,1,3-benzoxadiazole</strong> (0.17 g) (which can be prepared according to Org. Proc. Res. Dev., (2003), 7, 436-445 at page 437), triethylamine (0.11 g) and dichlorobistriphenyl-phosphine palladium (II) (0.12 g) were added to a solution of N- ({(5S)-3-[3-fluoro-4-(trimethylstannyl)phenyl]-2-oxo-1,3-oxazolidin-5- yl}methyl)acetamide (0.18 g) (which can be prepared according to Example 8 of WO 01/94342, page 52) in dry dimethyl formamide (15 mL) and the reaction mixture was heated at 100 C for about 3 hours, cooled and diluted with ethyl acetate. The organic layer was washed with water, dried over sodium sulfate and concentrated. The crude product was purified by column chromatography using 2 % methanol in dichloromethane as eluent to yield the title compound (0.14 g). Melting point: 156-165 C; EMS (m/z): 388 (M+H); 1HNMR(CDCB): delta 7.91 (m, 2H), 7.62 (m, 2H), 7.52 (t, 1H), 7.35 (dd, 1H), 6.10 (t, 1H), 4.84 (m, 1H), 4.12 (t, 1H), 3.87 (t, 1H), 3.71 (m,2H), 2.02 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine;bis-triphenylphosphine-palladium(II) chloride; In N,N-dimethyl-formamide; at 100℃; for 3h; | Triethylamine (0.12 g), <strong>[51376-06-8]5-bromo-2,1,3-benzoxadiazole</strong> (0.19 g) and dichlorobistriphenylphosphine palladium(II) (0.13 g) were added to a solution of N-({(5S)- 3 - [3 , 5 -difluoro-4-(trimethylstannyl)phenyl] -2-oxo- 1 ,3 -oxazolidin-5 -yl } methyl)acetamide (0.21 g) (which can be prepared according to Example 8 of WO 01/94342, at page 52) in dry dimethyl formamide (15 mL) and the reaction mixture was heated at 100 C for about 3 hours. The reaction mixture was filtered and diluted with ethyl acetate. The organic layer was washed with water, dried over sodium sulfate and concentrated. The crude EPO <DP n="44"/>product was purified by column chromatography using 2 % methanol in dichloromethane as eluent to yield the title compound (0.035 g).Melting point: 165-168 C; EMS (m/z): 388;1HNMR(CDC13): delta 7.92 (m, 2H), 7.48 (dd, 1H), 7.32 (dd, 2H), 5.98 (t, 1H), 4.85 (m, 1H), 4.09 (t, 1H), 3.84 (m, 1H), 3.72 (m, 2H), 2.03 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In N,N-dimethyl-formamide; at 100℃; for 17h; | <strong>[51376-06-8]5-bromo-2,1,3-benzoxadiazole</strong> (0.4 g), cesium carbonate (0.79 g), 2,2'- bis(diphenylphosphino)-1,1 '-binapthyl (0.1 g) and tris-(dibenzylideneacetone) dipalladium(O) (0.74 g were added) to (5R)-3-(3-fluoro-4-piperazin-1-ylphenyl)-5-(2H- l,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-2-one (0.7 g) (obtained from Step b) in dry dimethylformamide (15 mL) and the reaction mixture was heated at 100 C for about 17 hours. The reaction mixture was filtered, the solvent was evaporated and the crude product thus obtained was purified by column chromatography using 2 % methanol in dichloromethane to yield the title product (0.2g). Melting point: 215-220 C; EIMS (m/z): 465.21;1HNMR(DMSO): delta 7.91-7.83 (m,3H), 7.73 (d, 1H), 7.43 (dd, 1H), 7.13 (d, 2H), 6.89 (s, 1H), 5.18 (m, 1H), 4.86 (d, 2H), 4.22 (t, 1H), 3.91-3.86 (m, 1H), 3.48 (m, 4H), 3.14 (m, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In N,N-dimethyl-formamide; at 100℃; for 17h; | <strong>[51376-06-8]5-bromo-2,1,3-benzoxadiazole</strong> (0.61 g), cesium carbonate (1.2 g), 2,2'- bis(diphenylphosphino)-1,1' -binapthyl (0.51 g) and Tris -(dibenzylideneacetone) dipalladium(O) (0.11 g) were added to a solution (5R)-3-[3-fluoro-4-(piperidin-4- yloxy)phenyl]-5-(lH-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-2-one (1 g) (obtained from Step b) in dry dimethylformamide (10 mL) and the reaction mixture was heated at 100 C for about 17 hours. The reaction mixture was filtered and the solvent was evaporated. The crude product thus obtained was purified by column chromatography using 1 % methanol in dichloromethane to yield the title product (0.15g).Melting point: 148-150C; EIMS (m/z): 480.02;1HNMR(DMSO): delta 7.85 (d, 3H), 7.68 (d, 1H), 7.46 (dd, 1H), 7.28 (t, 1H), 7.15 (d, 1H), 6.85 (s, 1H), 5.2 (m, 1H), 4.86-4.85 (d, 2HO, 4.6 (m, 1HO, 4.22 (t, 1H), 3.9 (m, 1H), 3.72- 3.68 (m, 2H), 3.47-3.46 (d, 1H), 2.04 (m, 2H), 1.76 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In N,N-dimethyl-formamide; at 100℃; for 17h; | 5-bromo-2,1,3-benzoxadiazol (0.75 g), cesium carbonate (1.47 g), 2,2'- bis(diphenylphosphino)-1,1' -binapthyl (0.18 g) and Tris -(dibenzylideneacetone) dipalladium(O) (0.13 g) were added to a solution of (5S)-3-(3-fluoro-4-piperazin-1- ylphenyl)-5-[(isoxazol-3-ylamino)methyl]-1 ,3-oxazolidin-2-one (1.36 g) (obtained from Step b) in dry dimethylformamide(10 mL) and the reaction mixture was heated at 100 C for about 17 hours. The reaction mixture was filtered and the solvent was evaporated. The crude product thus obtained was purified by column chromatography using 1 % methanol in dichloromethane to yield the title product (0.1 g). Melting point: 213-215 C; EMS (m/z): 480.26, M+Na 502.22; EPO <DP n="49"/>1HNMR(DMSO): delta 8.38 (s, 1H), 7.88 (d, 1H), 7.72 (d, 1H), 7.53 (dd, 1H), 7.15 (m, 2H), 6.89 (s, 1H), 6.54 (t, 1H), 6.0 (s, 1H), 4.86 (m, 1H), 4.13 (t, 1H), 3.79 (t, 1H), 3.53 (m, 4H), 3.15 (m, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In N,N-dimethyl-formamide; at 100℃; for 17h; | 5-bromo-2,1,3-benzoxadiazol (2.74 g) (which can be prepared according to Org. Proc. Res. Dev., (2003), 7, 436-445), cesium carbonate (5.38 g), 2,2'- bis(diphenylphosphino)-1,1'-binapthyl (0.68 g) and tris-(dibenzylideneacetone) dipalladium(O) (0.5 g) were added to a solution of (5S)-3-[3-fluoro-4-(piperidin-4- yloxy)phenyl]-5-[(isoxazol-3-ylamino)methyl]-1,3-oxazolidin-2-one (5 g) (obtained from Step b) in dry dimethylformamide (15 mL) and the reaction mixture was heated at 100 C for about 17 hours. The reaction mixture was filtered and the solvent was evaporated. The crude product thus obtained was purified by column chromatography using 1 % methanol in dichloromethane to yield the title product (0.4g). Melting point: 134-140 C; EIMS (m/z): 495.25;1HNMR(DMSO): delta 8.41 (s, 1H), 7.88 (d, 1H), (d, 1H), 7.6 (dd, 1H), 7.32 (t, 1H), 7.25 (d, 1H), 6.88 (s, 1H), 6.56 (t, 1H), 6.03 (s, 1H), 4.8 (m, 1H), 4.63-4.62 (m, 1H), 4.17 (t, 1H), 3.81 (m, 4H), 3.49-3.43 (m, 3H), 2.07 (m, 2H), 1.8 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In N,N-dimethyl-formamide; at 100℃; for 17h; | <strong>[51376-06-8]5-bromo-2,1,3-benzoxadiazole</strong> (0.71 g), cesium carbonate (1.4 g), 2,2'- bis(diphenylphosphino)-1,r-binapthyl (0.17 g) and Tris-(dibenzylideneacetone) dipalladium(O) (0.13g) were added to a solution of (5S)-3-[3-fluoro-4-(piperidin-4- yloxy)phenyl]-5-[(isoxazol-3-ylamino)methyl]-1,3-oxazolidin-2-one (1.3 g) (obtained from Step b) in dry dimethylformamide (15 mL) and the reaction mixture was heated at 100 C for about 17 hours. The reaction mixture was filtered and the solvent was evaporated. The crude product thus obtained was purified by column chromatography using 1 % methanol in dichloromethane to yield the title product (0.07g).Melting point: 75-100 C; EIMS (m/z): 534.21; 1HNMR(DMSO): delta 8.16 (s, 1H), 7.66 (d, 1H), 7.48 (dd, 1H), 7.3 (m, 2H), 7.17 (d, 1H), 7.08-7.05 (t, 1H), 6.75 (s, 1H), 4.99 (m, 1H), 4.53 (m, 3H), 4.14-4.11 (t, 1H), 3.95 (t, 1H), 3.61 (m, 2H), 3.3 (m, 2H), 2.04 (m, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In N,N-dimethyl-formamide; at 100℃; for 17h; | <strong>[51376-06-8]5-bromo-2,1,3-benzoxadiazole</strong> (0.52 g), cesium carbonate (1.01 g), 2,2'- bis(diphenylphosphino)-1,1' -binapthyl (0.13 g) and tris-(dibenzylideneacetone) dipalladium(O) (0.09 g) were added to a solution of (5R)-3-(3-fluoro-4-piperazin-1- ylphenyl)-5-[(isoxazol-3-yloxy)methyl]-1,3-oxazolidin-2-one (0.91 g) (obtained from Step b) in dry dimethylformamide (15 mL) and heated at 100 C for about 17 hours. The reaction mixture was filtered and the solvent was evaporated. The crude product thus obtained was purified by column chromatography using 80 % ethyl acetate in hexane to yield the title product (0.03g).Melting point: 125-143 C; EIMS (m/z): 481.25; 1HNMR(DMSO): delta 8.69 (s, 1H), 7.88 (d, 1H), 7.73 (d, 1H), 7.53 (dd, 1H), 7.24 (d, 1H), 7.15 (t, 1H), 6.89 (s, 1H), 6.39 (s, 1H), 4.99 (m, 1H), 4.47 (m, 2H), 4.18 (t, 1H), 3.91 (t, 1H), 3.53 (m, 4H), 3.15 (m, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 80℃; for 48h; | <strong>[51376-06-8]5-bromo-2,1,3-benzoxadiazole</strong> (0.14 g) and diisopropyl ethylamine (1.16 mL) were added to a solution of tert-butyl 4-(4-{(5S)-5-[(acetyl amino)methyl]-2-oxo-1,3- EPO <DP n="54"/>oxazolidin-3-yl}-2-fluorophenoxy)piperidine-1-carboxylate (0.3 g) (which can be prepared according to Example 7 in Biorg. Med. Chem. Lett., 11 (2001), 1829-1832 at page 1830) in acetonitrile and the reaction mixture was heated at 80 C for about 48 hours. The reaction mixture was filtered and the solvent was evaporated. The crude product thus obtained was purified by preparative thin layer chromatography using 5 % methanol in dichloromethane to yield the title product (0.03 g).Melting point: 96-100 C; EIMS (m/z): 470.13;1HNMR(CDCl3): delta 7.6 (dd, 1H), 7.47 (dd, 1H), 7.30 (d, 1H), 7.06 (m, 2H), 6.73 (dd, 1H), 5.94 (6s, 1H), 4.76 (m, 1H), 4.49 (m, 1H), 4.03 (t, 1H), 3.76-3.44 (m, 6H, 3.28 (m, 1H), 2.03 (m, 7H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
523 mg (1.65 eq. ) bis (PINACOLATO) diboran, 552 mg (4.5 eq. ) potassium acetate and 51 mg (0.01 eq. ) PDCL (DPPF)-CH2CI2 are added to a solution of 373 mg 5-bromo-benzo [1,2, 5] oxa- DIAZOLE in 8 mL DMF and heated to 80C under continuous stirring for 6 hours. 662 mg (5 eq. ) sodium carbonate in 3.3 mL water are added together with 500 mg (1 eq. ) 2-bromo- N, N-dimethylaniline and 51 mg (0.01 eq. ) PDCL (dppf)-CH2CI2 to the reaction mixture, which is stirred for another 18 hours at 80C, cooled to room temperature and extracted with ethyl acetate and water. The combined organic phases are washed with brine, dried over magnesium sulfate and evaporated. The residue is column chromatographed (hexane, then HEXANE/ETHYL acetate 8: 1) to yield the desired product as an orange resin. MS (ES+): 240 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
500 mg (2.5 MMOL) 5-bromo-benzo [1,2, 5] oxadiazole and 313 mg (0.1 eq. ) tetrakis- (triphenylphosphine) palladium are stirred for 30 minutes at room temperature in 10 mL 1,2- dimethoxyethane. 533 mg (2 eq. ) sodium carbonate are dissolved in 1.8 mL water and added to the reaction mixture, followed by 663 mg (1.6 eq. ) 4- (dimethylamino) phenylboronic acid. After stirring at REFLUX FOR 18H, the reaction mixture is cooled to room temperature and extracted with ethyl acetate and water. The organic phases are combined, dried with magnesium sulfate, filtered and evaporated. The residue is column chromatographed (hexane, then HEXANE/ETHYL acetate 8: 1 then 5: 1) to yield the desired product as a yellow solid. MS (ES+): 240 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | In N,N-dimethyl-formamide; at 140℃; for 24h;Inert atmosphere; | To a stirred solution of 5-bromobenzo[c][l, 2, and 5] oxadiazole (2.0 g, 10.050 mmol) in DMF (50 mL) was added CuCN (1.79 g, 230.10 mmol) at RT under an inert atmosphere. The reaction mixture was then heated at 140 0C for 24 h., cooled to RT, diluted with water (10 mL) and stirred for 10 min. The precipitated solid was filtered off and the filtrate was concentrated in vacuo to obtain the crude product. The crude material was purified via silica gel column chromatography to afford benzo[c][l,2,5]oxadiazole-5- carbonitrile (0.7 g, 48 %) as a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With triethyl phosphite; In ethanol; at 60℃; for 1h;Inert atmosphere; | To a stirred solution of 5-bromobenzo[c][l,2,5]oxadiazole 1-oxide (6.0 g, 28.436 mmol) in ethanol (60 mL) was added triethyl phosphite (6.2 mL, 34.123 mmol) at RT under an inert atmosphere. The reaction mixture was then heated at 60 0C for 1 h., cooled to RT, diluted with hexane (100 mL) and stirred for 10 min. The precipitated solid was filtered off and the filtrate was concentrated in vacuo to obtain the crude product. The crude material was purified via silica gel column chromatography to afford 5- , bromobenzo[c][l,2,5] oxadiazole (4.0 g, 71%) as a light yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11% | Example 49: 5-(2,1,3-benzoxadiazol-5-yl)-/V-cyclopentyl-2-methylpyrimidin-4-amine:; In a flask under argon were placed 200 mg (1.00 mmles, 1.0 eq.) of 5-bromo-2,1,3- benzoxadiazole, 326 mg (1.10 mmoles, 1.10 eq.) of bis(pinacolato)diboron, 986 mg (3.32 mmoles, 3.30 eq.) of AcOK, and 8 mg (0.01 mmoles, 0.01 eq.) of PdCI2(dppf). 3.5 mL of anhydrous DMF were added and the mixture was stirred at 800C for 6h. It was cooled to RT and 170 mg (0.66 mmoles, 0.66 eq.) of 5-bromo-Lambda/-cyclopentyl-2-methylpyrimidin-4-amine, 8 mg (0.01 mmoles, 0.01 eq.) of PdCI2(dppf) were added followed by a solution of 352 mg (3.32 mmoles, 3.30 eq.) of Na2CO3 in 1.41 mL of water. The mixture was heated at 800C for 15h. The experiment was allowed to cool to RT. The solution was partitioned between 35 mL of water and 15 mL of AcOEt. The aqueous phase was extracted two more times with 15 mL of AcOEt. The combined organic layers were washed once with 15 mL of brine, dried over Na2SO4, filtered and evaporated to dryness. The crude compound was purified by flash chromatography on silica gel. The crude compound was then recrystallized in 1 mL of hot MeOH. The solution was cooled to RT, evaporated to the half and left overnight in the fridge. EPO <DP n="79"/>The solid was filtered off, washed with 2 ml. of Et2O and dried under high vacuum to give 34 mg of a yellow solid. Yield : 11 % M.P. : 165-167C LC-MS : Tr = 3.61 min. (100 %) (ES-MS: m/z 296.2 (M+H)) [Column : Nucleosil C-18HD, 4x70 mm, 3mum, gradient CH3CN/H2O/TFA 0.05% : 20-100% CH3CN (6 min.), 100% CH3CN (1.5 min.), flow : 1 mL/min].1H-NMR (CDCI3, 400 MHz) delta : 1.34-1.45 (m, 2H) ; 1.62-1.74 (m, 4H) ; 2.08-2.17 (m, 2H) ; 2.59 (s, 3H) ; 4.52 (quint, J = 7.0 Hz, 1H) ; 4.80 (d, J = 7.0 Hz, 1H) ; 7.42 (d, J = 9.5 Hz, 1H) ; 7.84 (s, 1H) ; 7.96 (d, J = 9.5 Hz, 1H) ; 8.04 (s, 1H).13C-NMR (CDCI3, 100 MHz) delta : 23.9 ; 26.1 ; 32.9 ; 52.2 ; 114.2 ; 115.5 ; 117.7 ; 132.9 ; 138.7 ; 148.4 ; 149.3 ; 153.9 ; 158.4 ; 168.1. |
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