Structure of 99071-54-2
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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. : | 99071-54-2 |
Formula : | C10H10N2 |
M.W : | 158.20 |
SMILES Code : | NCC1=CC=C2N=CC=CC2=C1 |
MDL No. : | MFCD02853688 |
InChI Key : | RZIPENSSTUBRAA-UHFFFAOYSA-N |
Pubchem ID : | 1514384 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.1 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 49.42 |
TPSA ? Topological Polar Surface Area: Calculated from |
38.91 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.57 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.06 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.54 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.22 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.07 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.49 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.04 |
Solubility | 1.45 mg/ml ; 0.00913 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.47 |
Solubility | 5.38 mg/ml ; 0.034 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.73 |
Solubility | 0.0293 mg/ml ; 0.000185 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 |
-6.51 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) |
1.0 |
* 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 |
---|---|---|
In ammonium hydroxide; | Similar to that described in ZH. OBSHCHKHIM OR (ENGLAUSFS 1325-1326) 1959, the crude 6-chloromethyl-quinoline (4.9 g) was carefully dissolved in NH4OH (700 mL) and stirred overnight at RT (the solution became orange). The mixture was filtered and the ammonia was evaporated on rotavap (bath at 34 C.). The solution was saturated with K2CO3. The yellow oil was removed and the aqueous phase was extracted with CHCl3. The organic phase was dried with K2CO3, filtered and evaporated to give quinolin-6-yl-methylamine. | |
With ammonium hydroxide; at 20℃; | Similar to that described in ZH. OBSHCHKHIM OR (ENGLAUSFS 1325-1326) 1959, the crude 6-chloromethyl-quinoline (4.9 g) was carefully dissolved in NH4OH (700 mL) and stirred overnight at RT (the solution became orange). The mixture was filtered and the ammonia was evaporated on rotavap (bath at 34 C.). The solution was saturated with K2CO3. The yellow oil was removed and the aqueous phase was extracted with CHCl3. The organic phase was dried with K2CO3, filtered and evaporated to give quinolin-6-yl-methylamine. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With triethylamine; at 130℃; for 5.0h;Microwave irradiation; | Example 52 (£)-2-(1 -(1 -(Quinolin-6-ylmethyl)-1 H-[1 ,2,3]triazolo[4,5-b]pyrazin-6-yl)ethylidene)hydrazinecarboxamide6-Bromo-N2-(quinolin-6-ylmethyl)pyrazine-2,3-diamine (52.1 )A mixture of <strong>[99071-54-2]quinolin-6-ylmethanamine</strong> (3.6g, 22.76mmol), 3,5-dibromopyrazin-2-amine (5.75 g, 22.76 mmol) and triethyl amine (4.61 g, 45.5 mmol) was heated in a microwave to130 0C for 5h. The reaction mixture was diluted with CH2CI2 and water and the organic layer was separated, washed with aqueous NH4CI, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography with EA:Hexanes to provide 6- bromo-N2-(quinolin-6-ylmethyl)pyrazine-2,3-diamine (6.93 g, 92%). LCMS (method A): [MH]+ = 330, tR = 4.89 min. |
92% | With triethylamine; at 130℃; for 5.0h;Microwave irradiation; | A mixture of <strong>[99071-54-2]quinolin-6-ylmethanamine</strong> (3.6g, 22.76mmol), 3,5-dibromopyrazin-2-amine (5.75 g, 22.76 mmol) and triethyl amine (4.61 g, 45.5 mmol) was heated with microwave irradiation at 130 0C for 5 h. The reaction mixture was diluted with CH2CI2 and water and the organic layer was separated, washed with aqueous NH4CI, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography withEtOAc:hexanes to provide 6.93 g (92%) of the title compound. LCMS (method A): [MH]+ = 330, tR = 4.89 min. |
59% | With N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one; at 180℃; for 12.0h;Sealed tube; | 2-Amino-3,5-dibromopyrazine (a, 6.1 g, 24.1 mmol),<strong>[99071-54-2]quinolin-6-ylmethanamine</strong> (b1, 3.8 g,24.1 mmol) and DIPEA (8.6 ml, 52.1 mmol) were dissolved in NMP (20 ml), thenthe mixture was stirred overnight at 180C in a sealed tube. After removal ofsolvents, the residue was purified by flash column chromatography to afford6-bromo-N2-(quinolin-6-ylmethyl)pyrazine-2,3-diamineas a yellow solid (c1, 4.7 g, 59%yield). LC-MS (ESI): [M+H]+=330. 1H NMR (400 MHz, DMSO-d6) delta 8.85 (dd, J1=4.4Hz, J2=1.6 Hz, 1H), 8.33(d, J=8.4 Hz, 1H), 7.99 (d, J=8.8 Hz, 1H)7.87(s, 1H), 7.73 (dd, J1=8.8Hz, J2=2.0 Hz, 1H), 7.50(dd, J1=8.4 Hz, J2=4.4 Hz, 1H), 7.21 (s, 1H),7.16 (t, J=5.6 Hz, 1H), 6.25 (s, 2H), 4.69 (d, J=5.6 Hz, 2H). |
59% | With N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one; at 130℃;Inert atmosphere; | 3,5-Dibromopyrazin-2-amine (6.1 g, 24 mmol), 6-quinolinemethyleneamine (3.8 g, 24 mmol) And N,N-diisopropylethylamine (DIPEA) (8.6 mL, 48 mmol) were added to NMP (20 mL) The reaction was carried out overnight at 130 C under argon. The reaction mixture was evaporated to remove DIPEA. The residue was poured into water (100 mL) and extracted with dichloromethane (30 mL x 3). The organic phase was washed with water and washed with brine. After drying, flash column chromatography gave 4.7 g of tan product. Yield: 59%. |
49% | With N-ethyl-N,N-diisopropylamine; at 130℃; for 5.0h; | Method 3 6-bromo-N2-(quinolin-6-ylmethyl)pyrazine-2,3-diamine: A mixture of <strong>[99071-54-2]quinolin-6-ylmethanamine</strong> (13 g, 82 mmol), 3,5-dibromopyrazin-2-amine (21 g, 82 mmol) and di-isopropylethylamine (16 mL, 89 mmol) was heated to 130 C. for five hours. The reaction was diluted with dichloromethane:ethanol (9:1) and the resulting suspension was filtered. The precipitate was washed sequentially with water and ether and air dried to afford 6-bromo-N2-(quinolin-6-ylmethyl)pyrazine-2,3-diamine (13 g, 49%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; triphenylphosphine; In tetrahydrofuran; | Step 227c. 6-(aminomethyl)quinoline 6-(azidomethyl)quinoline (320 mg) and triphenylphosphine (880 mg) were dissolved in 7 mL THF. The reaction mixture was treated with 0.5 mL of H2 O and refluxed for 7 hours. The reaction mixture was cooled and partitioned between Et2 O and 1N HCl. The aqueous portion was then treated with 1N NaOH until basic and extracted into EtOAc. The organic portion was dried over Na2 SO4 and concentrated under reduced pressure to give the title compound (70 mg) as a brown oil. MS(CI) m/e 159 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; | a (R)-N5 -[Amino(nitroimino)methyl]-N-[(6-quinolinyl)methyl]-N2 -(diphenylacetyl)-ornithinamide Prepared analogously to Example 87a) from (R)-N5 -[amino(nitroimino)methyl]-N2 -(diphenylacetyl)-ornithine, 6-quinoline-methanamine (prepared from 6-methylquinoline via 6-quinoline-carboxaldehyde [selenium dioxide] and reductive amination thereof [ammonium acetate/sodium cyanoborohydride]) and TBTU in a yield of 40% of theory. Colourless crystals, mp. 222-224 C. IR (KBr): 1637.5 cm-1 (amide-C=O) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | With hydrazine hydrate; In methanol; for 3.0h;Reflux; | Quinolin-6-ylmethanamine (intermediate D) To a solution of 2-(quinolin-6-ylmethyl)isoindoline-1 ,3-dione (2Og, 69.4 mmol) in MeOH (100 mL), was added hydrazine hydrate (3.47 g, 69.4 mmol). The solution was heated to reflux for 3h, then cooled to rt, filtered through celite. The filtrate was concentrated in vacuo and EtOAc was added to dilute the residue, filtered and concentrated in vacuo to afford 6-bromo- N2-(quinolin-6-ylmethyl)pyrazine-2,3-diamine (5g) in 41 % yield 41 %. LCMS (method B): [MH]+ = 159, tR = 0.93 min. |
41% | With hydrazine hydrate; In methanol; for 3.0h;Reflux; | To a solution of 2-(quinolin-6-ylmethyl)isoindoline-1 ,3-dione (2Og, 69.4 mmol) in MeOH (100 mL) was added hydrazine monohydrate (3.47 g, 69.4 mmol). The solution was heated at reflux for 3 h, then cooled to rt and filtered through celite. The filtrate was concentrated in vacuo. EtOAc then was added to the residue and the resulting solution was filtered and concentrated in vacuo to afford 5 g (41 %) of the title compound. LCMS (method B): [MH]+ = 159, tR = 0.93 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With hydrogen;Raney-Ni; In methanol; ammonia; at 20℃; under 760.051 Torr; for 16.0h; | Step 5: Quinolin-6-ylmethanamine To a solution of quinoline-6-carbonitrile (96 g, 0.62 mol) in saturated ammonia in methanol (1 lit.), Raney-Ni (10 g) was added and the mixture was stirred at 1 atm of H2 at RT for 16 h. The reaction mixture was filtered and the filtrate was concentrated under vacuum to afford the title compound as a brown oil (80 g, 82%). 1H-NMR (delta ppm, DMSO-d6, 400 MHz): delta 8.83 (dd, J=4.2, 1.7 Hz, 1H), 8.29 (d, J=8.3 Hz, 1H), 7.95 (d, J=8.6 Hz, 1H), 7.85 (s, 1H), 7.75 (dd J=8.7, 1.8 Hz, 1H), 7.49 (dd, J=8.2, 4.2 Hz, 1H), 3.90 (s, 2H). |
82% | With ammonia; hydrogen; In methanol; at 20℃; under 760.051 Torr; for 16.0h; | To a solution of quinoline-6-carbonitrile (96 g, 0.62 mol) in saturated ammonia in methanol (1 lit.), Raney-Ni (10 g) was added and the mixture was stirred at 1 atm of H2 at RT for 16h. The reaction mixture was filtered and the filtrate was concentrated under vacuum to afford the title compound as a brown oil (80 g, 82%). 'H-NMR (delta ppm, DMSO-d6, 400 MHz): delta 8.83 (dd, J = 4.2, 1.7 Hz, 1H), 8.29 (d, J = 8.3 Hz, 1H), 7.95 (d, J = 8.6 Hz, 1H), 7.85 (s, 1H), 7.75 (dd J = 8.7,1.8 Hz, 1H), 7.49 (dd, 7 = 8.2,4.2 Hz, 1H), 3.90 (s, 2H). |
82% | With ammonia; hydrogen; In methanol; at 20℃; under 760.051 Torr; for 16.0h; | Step 5: Quinolin-6-ylmefhanamine: To a solution of quinoline-6-carbonitrile (96 g, 0.62 mol) in saturated ammonia in methanol (1 lit.), Raney-Ni (lOg) was added and the mixture was stirred at 1 atm of H2 at RT for 16h. The reaction mixture was filtered and the filtrate was concentrated under vacuum to afford the title compound as a brown oil (80 g, 82%). 'H-NMR (delta ppm, DMSO-d6, 400 MHz): delta 8.83 (dd, J = 4.2, 1.7 Hz, 1H), 8.29 (d, J = 8.3 Hz, 1H), 7.95 (d, J = 8.6 Hz, 1H), 7.85 (s, 1H), 7.75 (dd J = 8.7,1.8 Hz, 1H), 7.49 (dd, J = 8.2,4.2 Hz, 1H), 3.90 (s, 2H). |
82% | With ammonia; hydrogen; In methanol; at 20℃; under 760.051 Torr; for 16.0h; | Step 5: Quinolin-6-ylmethanamine To a solution of quinoline-6-carbonitrile (96 g, 0.62 mol) in saturated ammonia in methanol (1 lit.), Raney-Ni (10 g) was added and the mixture was stirred at 1 atm of H2 at RT for 16 h. The reaction mixture was filtered and the filtrate was concentrated under vacuum to afford the title compound as a brown oil (80 g, 82%). 1H-NMR (delta ppm, DMSO-d6, 400 MHz): delta 8.83 (dd, J=4.2, 1.7 Hz, 1H), 8.29 (d, J=8.3 Hz, 1H), 7.95 (d, J=8.6 Hz, 1H), 7.85 (s, 1H), 7.75 (dd J=8.7, 1.8 Hz, 1H), 7.49 (dd, J=8.2, 4.2 Hz, 1H), 3.90 (s, 2H). |
79% | With ammonia; hydrogen; In methanol; under 22502.3 Torr; | The intermediateA-2 (4.7 g, 30.5 mmol) was dissolvedin NH3-MeOH (7 mol/L, 50 ml), H-cube machine (30 bar, 25,1 ml/min, Raney Ni) was used and the crude product was further purified byflash column chromatography to afford the title compound as a white solid (3.8 g, 79% yield). LC-MS (ESI): [M+H]+=159.1H NMR (400 MHz, DMSO-d6)delta 8.84 (dd, J1=4.0Hz, J2=1.2 Hz, 1H), 8.28 (d, J=8.0Hz, 1H), 7.96 (d, J=8.4 Hz, 1H), 7.88 (s, 1H), 7.76 (d, J= 8.4Hz, 1H), 7.48 (dd, J1=8.0Hz, J2=4.0 Hz, 1H), 3.97 (s, 2H). |
79% | With ammonia; hydrogen; In methanol; at 25℃; under 22502.3 Torr; | 6-Cyanoquinoline A-2 (4.7 g, 30 mmol) was dissolved in a methanolic ammonia solution (7 mol / L, 50 mL) Hydrogenation reduction was performed using a hydrogenation instrument H-cube (30 bar, 25 C, flow rate 1 mL / min, Raney Ni) The crude product was obtained and isolated in reverse phase to give 3.8 g of quinoline-6-methyleneamine A, yield: 79% |
A446799 [114223-89-1]
Quinolin-6-ylmethanamine hydrochloride
Reason: Free-Salt