Structure of 146394-99-2
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CAS No. : | 146394-99-2 |
Formula : | C9H18N2O2 |
M.W : | 186.25 |
SMILES Code : | O=C(OC(C)(C)C)NC/C=C/CN |
MDL No. : | MFCD09752966 |
InChI Key : | BWNIUPOJWUXWMX-SNAWJCMRSA-N |
Pubchem ID : | 18947920 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.67 |
Num. rotatable bonds | 6 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 52.12 |
TPSA ? Topological Polar Surface Area: Calculated from |
64.35 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.27 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.3 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.03 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.84 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.37 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.96 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.79 |
Solubility | 30.4 mg/ml ; 0.163 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.21 |
Solubility | 11.4 mg/ml ; 0.0611 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.37 |
Solubility | 7.89 mg/ml ; 0.0424 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 |
-7.22 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 |
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) |
2.69 |
* 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 triethylamine; In methanol; at 20℃;Heating / reflux; | (E)-l,4-diaminobut-2-ene dihydrochloride (8.0 g, 50mrnol) was suspended in 10% TEA/ MeOH solution (120ml). To the above suspension TEA (14ml) was added. A solution of di-tert-butyldicarbonate (3.7g, 16.8mmol) in methanol (10ml) was added drop- wise to the vigorously stirred mixture. The reaction mixture was refluxed for 3 h, and stirred at room temperature overnight. After the removal of the precipitate, the filtrate was evaporated to dryness. The crude residue was purified by column chromatography with CH2Cl2-MeOH (20:1) to give 1.5g of the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride;dmap; In dichloromethane; at 20℃; | To a solution of <strong>[146394-99-2](4-amino-but-2-enyl)-carbamic acid tert-butyl ester</strong> (1.Og, 5.36mmol) in dry CH2Cl2 (40 ml) was added 6,6-bis-(4-fluorophenyl)-hexanoic acid (1.62g, 5.36mmol) under nitrogen. To the reaction was added EDC (2.04g, 10.72mmol) and DMAP (cat) and the reaction mixture stirred under nitrogen at room temperature overnight. The reaction was then concentrated under reduced pressure. The residue dissolved in ethyl acetate: water (10:1) (150ml). The organic was washed with water (30ml, 2x) and 10% NaOH (30 ml) and dried over MgSO4 and evaporated to dryness. The resulting residue was purified by column chromatography using CH2C12:CH3OH (15:1) to give the desired product in 70% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With N-ethyl-N,N-diisopropylamine; In ethanol; at 120℃;Sealed tube; | To a suspension of 4-chloro-3-methoxy-5-nitrobenzamide (1.50 g, 6.50 mmol) in EtOH (25 mL) was added (E)-tert-buty (4-aminobut-2-en-l-yl)carbamate (1.45 g, 7.81 mmol) and DIEA (3.41 mL, 19.5 mmol). The reaction was heated to 120 C in a sealed tube overnight and allowed to cool to RT. The resulting orange precipitate was collected by filtration and washed with EtOH to provide the title compound (2.1 g, 5.5 mmol, 85 % yield). LCMS (LCMS Method D): Rt = 0.96 min, [M+H]+ = 439.2 |
85% | With di-tert-butyl diisopropylphosphoramide; In ethanol; at 120℃;Sealed tube; | To a suspension of 4-chloro-3-methoxy-5-nitrobenzamide (1.50 g, 6.50 mmol) in EtOH(25 mL) was added (E)-tett-butyl (4-aminobut-2-en-1-yl)carbamate (1.45 g, 7.81 mmol) andDIEA (3.41 mL, 19.5 mmol). The reaction was heated to 120 C in a sealed tube overnightand allowed to cool to RT. The resulting orange precipitate was collected by filtration andwashed with EtOH to provide the title compound (2.1 g, 5.5 mmol, 85 % yield). LCMS (LCMSMethod D): Rt = 0.96 mi [M+H] = 439.2 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With potassium carbonate; In dimethyl sulfoxide; at 20℃; | A mixture of 4-fluoro-3-nitrobenzamide (10.0 g, 54.3 mmol), (E)-tert-buty (4- aminobut-2-en-l-yl)carbamate (10.62 g, 57.0 mmol) and K2CO3 (15.01 g, 109 mmol) in DMSO (200 mL) was stirred at RT overnight. The reaction was poured into water (2000 mL) and stirred for 30 min. The resulting solid was collected by filtration to yield the title compound (18.3 g, 52.2 mmol, 96 % yield). LCMS (LCMS Method A): Rt = 1.38 min, [2M+H]+ = 700.5 |
96% | With potassium carbonate; In dimethyl sulfoxide; at 20℃; | A mixture of 4-fluoro-3-nitrobenzamide (10.0 g, 54.3 mmol), (£)-fert-butyl (4- aminobut-2-en-l-yl)carbamate (10.62 g, 57.0 mmol) and K2CO3 (15.01 g, 109 mmol) in DMSO (200 mL) was stirred at RT overnight. The reaction was poured into water (2000 mL) and stirred for 30 min. The resulting solid was collected by filtration to yield the title compound ( 18.3 g, 52.2 mmol, 96 % yield). LCMS (LCMS Method A): Rt = 1.38 min, [2M+H]+ = 700.5 |
96% | With potassium carbonate; In dimethyl sulfoxide; at 20℃; | A mixture of 4-fluoro-3-nitrobenzamide (10.0 g, 54.3 mmol), <strong>[146394-99-2](E)-tert-butyl (4-aminobut-2-en-1-yl)carbamate</strong> (10.62 g, 57.0 mmcl) and K2C03 (15.01 g, 109 mmcl) in DMSO(200 mL) was stirred at RT overnight. The reaction was poured into water (2000 mL) and stirred for 30 mm. The resulting solid was collected by filtration to yield the title compound (18.3 g, 52.2 mmol, 96 % yield). LCMS (LCMS Method A): Rt = 1.38 mi [2M+H] = 700.5 |
96% | With potassium carbonate; In dimethyl sulfoxide; at 20℃; | A mixture of 4-fluoro-3-nitrobenzamide (10.0 g, 54.3 mmol), (E)-tert-butyl (4- aminobut-2-en-1-yl)carbamate (10.62 g, 57.0 mmol) and K2CO3(15.01 g, 109 mmol) in DMSO (200 mL) was stirred at room temperature overnight. The reaction was poured into water (2000 mL) and stirred for 30 min. The resulting solid was collected by filtration to yield the title compound (18.3 g, 52.2 mmol, 96% yield). LCMS [2M+H]+= 700.5 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With N-ethyl-N,N-diisopropylamine; In ethanol; at 120℃;Sealed tube; | To a suspension of 4-chloro-3-methoxy-5-nitrobenzamide (1.50 g, 6.50 mmol) in EtOH (25 mL) was added (B-tert-buty (4-aminobut-2-en-l-yl)carbamate (1.454 g, 7.81 mmol) and DIEA (3.4 mL, 20 mmol). The reaction was stirred at 120 C in a sealed tube overnight and allowed to cool to RT. The resulting orange solid was collected by filtration and washed with EtOH to afford the title compound (2.10 g, 5.52 mmol, 85 % yield). *H NMR (400 MHz, DMSO-t) delta ppm 8.19 (d, J=1.77 Hz, 1 H) 8.03 (br. s., 1 H) 7.76 (t, J=6.08 Hz, 1 H) 7.55 (d, J=1.52 Hz, 1 H) 7.34 (br. s., 1 H) 6.95 (t, J=5.45 Hz, 1 H) 5.53 (br. s., 2 H) 4.09 (br. s., 2 H) 3.88 (s, 3 H) 3.48 (br. s., 2 H) 1.35 (s, 9 H); LCMS (LCMS Method D): Rt = 0.89 min, [M-t- Bu+H]+ = 325.1 |
85% | With N-ethyl-N,N-diisopropylamine; In ethanol; at 120℃;Sealed tube; | To a suspension of 4-chloro-3-methoxy-5-nitrobenzamide (1.50 g, 6.50 mmol) in EtOH (25 mL) was added (E)-tett-butyl (4-aminobut-2-en-1-yl)carbamate (1.454 g, 7.81 mmol) and DIPEA (3.4 mL, 20 mmol). The reaction was stirred at 120 C in a sealed tube overnight andallowed to cool to RT. The resulting orange solid was collected by filtration and washed with EtOH to afford the title compound (2.10 g, 5.52 mmol, 85 % yield). 1H NMR (400 MHz, DMSOd6) ppm 8.19 Cd, J=l.77 Hz, 1 H) 8.03 (br. s., 1 H) 7.76 Ct, J=6.08 Hz, 1 H) 7.55 Cd, J=1.52 Hz, 1 H) 7.34 (br. s., 1 H) 6.95 Ct, J=5.45 Hz, 1 H) 5.53 (br. s., 2 H) 4.09 (br. s., 2 H) 3.88 Cs, 3 H) 3.48 (br. s., 2 H) 1.35 Cs, 9 H). LCMS (LCMS Method D): Rt = 0.89 mi [M-t-Bu+H] =325.1 |
85% | With N-ethyl-N,N-diisopropylamine; In ethanol; at 120℃;Sealed tube; | To a suspension of 4-chloro-3-methoxy-5-nitrobenzamide (1.50 g, 6.50 mmol) in EtOH (25 mL) was added (£)-tert-butyl (4-aminobut-2-en-l-yl)carbamate (1.454 g, 7.81 mmol) and DIEA (3.4 mL, 20 mmol). The reaction was stirred at 120 C in a sealed tube overnight and allowed to cool to RT. The resulting orange solid was collected by filtration and washed with EtOH to afford the title compound (2.10 g, 5.52 mmol, 85 % yield). NMR (400 MHz, DMSO-tfc) delta ppm 8.19 (d, J=1.77 Hz, 1 H) 8.03 (br. s., 1 H) 7.76 (t, J=6.08 Hz, 1 H) 7.55 (d, J=1.52 Hz, 1 H) 7.34 (br. s., 1 H) 6.95 (t, J=5.45 Hz, 1 H) 5.53 (br. s., 2 H) 4.09 (br. s., 2 H) 3.88 (s, 3 H) 3.48 (br. s., 2 H) 1.35 (s, 9 H); LCMS (LCMS Method D): Rt = 0.89 min, [M-i-Bu+H]+ = 325.1 |
85% | With N-ethyl-N,N-diisopropylamine; In ethanol; at 120℃;Sealed tube; | To a suspension of 4-chloro-3-methoxy-5-nitrobenzamide (1.50 g, 6.50 mmol) in EtOH (25 mL) was added (E)-tett-butyl (4-aminobut-2-en-1-yl)carbamate (1.454 g, 7.81 mmol) and DIEA (3.4 mL, 20 mmol). The reaction was stirred at 120 C in a sealed tube overnight and allowed to cool to RT. The resulting orange solid was collected by filtration and washed withEtOH to afford the title compound (2.10 g, 5.52 mmol, 85 % yield). 1H NMR (400 MHz, DMSO-d6) ppm 8.19 Cd, J=1.77 Hz, 1 H) 8.03 (br. s., 1 H) 7.76 Ct, J=6.08 Hz, 1 H) 7.55 Cd, J=1.52 Hz, 1 H) 7.34 Cbr. 5., 1 H) 6.95 Ct, J=5.45 Hz, 1 H) 5.53 Cbr. 5., 2 H) 4.09 Cbr. 5., 2 H)3.88 Cs, 3 H) 3.48 Cbr. s., 2 H) 1.35 Cs, 9 H); LCMS CLCMS Method D): Rt = 0.89 mi [M-tBu+H] = 325.1 |
85% | With N-ethyl-N,N-diisopropylamine; In ethanol; at 120℃;Sealed tube; | To a suspension of 4-chloro-3-methoxy-5-nitrobenzamide (1.50 g, 6.50 mmol) in EtOH (25 mL) was added <strong>[146394-99-2](E)-tert-butyl (4-aminobut-2-en-1-yl)carbamate</strong> (1.454 g, 7.81 mmol) and DIEA (3.4 mL, 20 mmol). The reaction was stirred at 120 C in a sealed tube overnight and allowed to cool to room temperature. The resulting orange solid was collected by filtration and washed with EtOH to afford the title compound (2.10 g, 5.52 mmol, 85% yield). 1H NMR (400 MHz, DMSO-d6) delta ppm 8.19 (d, J=1.77 Hz, 1 H) 8.03 (br. s., 1 H) 7.76 (t, J=6.08 Hz, 1 H) 7.55 (d, J=1.52 Hz, 1 H) 7.34 (br. s., 1 H) 6.95 (t, J=5.45 Hz, 1 H) 5.53 (br. s., 2 H) 4.09 (br. s., 2 H) 3.88 (s, 3 H) 3.48 (br. s., 2 H) 1.35 (s, 9 H). LCMS (m/z): 325.1 [M-t-Bu + H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With N-ethyl-N,N-diisopropylamine; In isopropyl alcohol; at 25℃; for 96.0h; | To a solution of <strong>[146394-99-2]tert-butyl (E)-(4-aminobut-2-en-1-yl)carbamate</strong> (2.2 g, 11.81 mmol) and DIEA (4.37 mL, 25.00 mmol) in isopropanol (30 mL) at 25 C was added 1-bromo-2- fluoro-3-nitrobenzene (2.5 g, 11.36 mmol). The reaction mixture was then stirred at 25 C for 4 days. The reaction mixture was concentrated. The resulting material was partitioned between water and EtOAc. The aqueous layer was separated and extracted with EtOAc (1x). The combined organic layers were then washed with brine, dried with magnesium sulfate, and concentrated to obtain the tert-butyl (E)-(4-((2-bromo-6-nitrophenyl)amino)but- 2-en-1-yl)carbamate (4.6 g, 12 mmol, 100% yield) as a yellow solid. The isolated material was used without any further purification. LCMS (m/z): 332.0 ([M + H]+- t-butyl). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In dimethyl sulfoxide; at 100℃;Sealed tube; | To a vial was added 3-(3-((tert-butyldimethylsilyl)oxy)propoxy)-4-chloro-5-nitrobenzamide (1.004 g, 2.58 mmol), <strong>[146394-99-2]tert-butyl (E)-(4-aminobut-2-en-1-yl)carbamate</strong> (Ark Pharm, cat No.AK308564: 0.481 g, 2.58 mmol), DMSO (12.91 ml), and DIPEA (2.254 ml, 12.91 mmol). The mixture was sealed, then heated at 100 C. overnight with stirring. After cooling to rt, the mixture was diluted with water and extracted with CHCl3/IPA (3:1). The combined organic extracts were dried over MgSO4, filtered, and concentrated in vacuo to provide the desired product as a brown oil. LC-MS calculated for C25H43N4O7Si (M+Na)+: m/z=561.3; found 561.3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In dimethyl sulfoxide; at 70℃; for 12.0h; | To a solution of 4-fluoro-3-methoxy-5-nitrobenzamide (300.0 mg, 1.401 mmol), <strong>[146394-99-2]tert-butyl (E)-(4-aminobut-2-en-1-yl)carbamate</strong> (391 mg, 2.101 mmol) in dry DMSO (2335 mul) was added K2CO3 (387 mg, 2.80 mmol). The resulting solution was heated at 70 C. for 12 h. The mixture was concentrated under reduced pressure, and then extracted with DCM and water. The combined organic layers were dried, filtered, and concentrated in vacuo. The crude residue was purified by flash chromatography on a silica gel column to afford the desired product. LC-MS calculated for C17H24N4NaO6 (M+Na)+: m/z=403.2; found 403.2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In dimethyl sulfoxide; at 20℃; for 1.0h; | To a solution of 4-fluoro-3-methyl-5-nitrobenzamide (0.400 g, 2.019 mmol) and <strong>[146394-99-2]tert-butyl (E)-(4-aminobut-2-en-1-yl)carbamate</strong> (0.376 g, 2.019 mmol) (Ark Pharm, cat No.AK308564) in dry DMSO (2.019 ml) was added K2CO3 (0.614 g, 4.44 mmol). The resulting yellow solution was stirred at room temperature for 1 h. The reaction mixture was diluted with water (15 mL) dropwise. The precipitated solid was filtered and then washed with water (10 mL). The resulting solid residue was dried to provide the desired product as a yellow solid. LC-MS calculated for C17H24N4NaO5 (M+Na)+: m/z=387.2; found 387.2. | |
With potassium carbonate; In dimethyl sulfoxide; at 20℃; for 1.0h; | To a solution of 4-fluoro-3-methyl-5-nitrobenzamide (0.400 g, 2.019 mmol) and <strong>[146394-99-2]tert-butyl (E)-(4-aminobut-2-en-1-yl)carbamate</strong> (0.376 g, 2.019 mmol) (Ark Pharm, cat No.AK308564) in dry DMSO (2.019 mL) was added K2CO3 (0.614 g, 4.44 mmol).;The resulting yellow solution was stirred at room temperature for 1 h. The reaction mixture was diluted with water (15 mL) dropwise. The precipitated solid was filtered and then washed with water (10 mL). The resulting solid residue was dried to provide the desired product as a yellow solid. LC-MS calculated for C17H24N4NaO5 (M+Na)+: m/z=387.2; found 387.2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In ethanol; at 80 - 120℃;Sealed tube; | To a vial was added <strong>[146394-99-2]tert-butyl (E)-(4-aminobut-2-en-1-yl)carbamate</strong> (Ark Pharm, cat No.AK308564: 0.140 g, 0.752 mmol), 7-chloro-6-nitrobenzofuran-4-carboxamide (Example 2, Step 5, 0.181 g, 0.752 mmol), a stir bar, EtOH (3.76 mL), and DIPEA (0.656 mL, 3.76 mmol). The resulting mixture was sealed and heated at 80 C. overnight, then 120 C. for 8 h. After cooling to rt, the mixture was concentrated and used directly in the next step. LC-MS calculated for C18H22N4O6Na (M+Na)+: m/z=413.2; found 413.2. |