Structure of 1190320-08-1
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CAS No. : | 1190320-08-1 |
Formula : | C8H6FN3 |
M.W : | 163.15 |
SMILES Code : | NC1=NC=NC2=CC=C(F)C=C12 |
MDL No. : | MFCD12024574 |
InChI Key : | ARIXAZJLBIBWSR-UHFFFAOYSA-N |
Pubchem ID : | 46835706 |
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 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 43.9 |
TPSA ? Topological Polar Surface Area: Calculated from |
51.8 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.44 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.38 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.78 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.5 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.63 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.55 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.34 |
Solubility | 0.75 mg/ml ; 0.0046 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.07 |
Solubility | 1.39 mg/ml ; 0.00849 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.24 |
Solubility | 0.0941 mg/ml ; 0.000577 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 |
-6.32 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) |
1.51 |
* 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 |
---|---|---|
80% | at 200.0℃; for 1.0h;Microwave irradiation; Sealed vial; | General procedure: Method A: Benzonitriles were suspended in formamide (40 equiv) and InCl3 (1 equiv), or not, in a sealed vial and were irradiated at 400 W under microwaves. The residue was cooled to room temperature, filtrated, washed with water and dried. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With tris-(dibenzylideneacetone)dipalladium(0); palladium diacetate; caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; XPhos; In 1,4-dioxane; at 100.0℃; for 2.0h;Inert atmosphere; | To a solution of 100 mg (321 pmol) 6-bromo-8-methyl-2H-spiro[cyclohexane-1 3- imidazo[1,5-a]pyridine]-1,5-dione (GAS-No: 1849592-70-6; PGT Int. AppI. (2015), WO 2015200481) and 57.7 mg (353 pmol) <strong>[1190320-08-1]6-fluoroquinazolin-4-amine</strong> (GAS-No: 1190320-08-1) in 12 mL 1 ,4-dioxane was added 314 mg cesium carbonate and the mixture was degassed and purged with argon several times. 19.9 mg 4,5-bis(diphenylphosphino)-9,9-dim ethylxanthene, 16.4 mg 2-(dicyclohexyl-phosphino)-2,4,6-triisopropylbiphenyl, 7.7 mg palladium(ll)acetate and 31.5 mg tris(dibenzylideneacetone)dipalladium(0) were added and the mixture was stirred at 1000 for 2 hours. The m ixture was concentrated and the residue purified by flash chromatography (Biotage SNAP Ultra cartridge silica 25 g, ethanol:dichloromethane) and crystallization from ethanol to give 73 mg (55%) of the titlecompound.LG-MS: m/z = 394.3[M÷H].1HNMR (400 MHz, DMSO-d6), 6 [ppm]= 1.24 (1H), 1.51 (2H), 1.59-1.81 (5H), 2.52 (3H*),3.02(2H), 7.85(1H), 7.95 (1H), 8.12(1H), 8.62 (1H), 8.79(1H), 9.33 (1H), 10.25(1H)*: at least partially hidden by solvent or water signal |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
31% | With tris-(dibenzylideneacetone)dipalladium(0); palladium diacetate; caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; XPhos; In 1,4-dioxane; at 105.0℃; for 2.0h;Inert atmosphere; | To a solution of 6?-bromo-8?-methyl-2?H-spiro[cyclopentane-1 ,3?-imidazo[l ,5-a]pyridine]-1 ?5?- dione (GAS 1849592-55-7; PGT Int. AppI. (2015), WO 2015200481, 100 mg, 337 pmol) and <strong>[1190320-08-1]6-fluoroquinazolin-4-amine</strong> (GAS 1190320-08-1, 60.4 mg, 370 pmol) in 1,4-dioxane (12 mL)was added cesium carbonate (329 mg, 1 .01 mmol) and the mixture was degassed and purged with argon several times. 4, 5-Bis(diphenylphosphino)-9,9-dimethylxanthene (20.8 mg, 36.0 pmol), 2-(dicyclohexyl-phosphino)-2,4,6-triisopropylbiphenyl (17.2 mg, 36.0 pmol), palladium(ll)acetate (8.08 mg, 36.0 pmol) and tris(dibenzylideneacetone)dipalladium(0) (33.0 mg, 36.0 pmol) were added and the mixture was stirred at 1050 for2 hours. The reaction mixture was diluted with a mixture of dichloromethane/methanol, anorganic salts were filtered off and the filtrate was concentrated. The residue was purified by preperative TLG (ethanol: dichloromethane) and the obtained material was taken up in dichloromethane/methanol and stirred at RT. The solid was isolated by centrifugation and dried to give 42 mg (31% yield) of the title compound.LG-MS: m/z = 380.1 [M÷H].1H-NMR (400 MHz, DMSO-d6) 6 [ppm]= 1.717 (4.64), 1.731 (5.23), 1.748 (4.64), 1.762(4.15), 1 .844 (5.33), 1.855 (5.53), 1 .874 (4.44), 1 .993 (6.32), 2.331 (3.36), 2.336 (1 .38),2.518 (16.00), 2.523 (10.67), 2.673 (3.06), 2.678 (1.38), 2.805 (2.96), 2.825 (5.53), 2.842(5.04), 2.857 (5.23), 2.877 (2.47), 3.297 (1 .09), 3.368 (1.68), 5.758 (2.57), 7.811(2.07),7.818 (2.37), 7.834 (4.44), 7.840 (4.94), 7.855 (3.16), 7.862 (3.36), 7.922 (5.04), 7.935(5.33), 7.944 (3.85), 7.957 (3.36), 8.141 (4.54), 8.147 (4.74), 8.164 (4.64), 8.170 (4.44), 8.546 (0.59), 8.606 (10.77), 8.776 (12.74), 9.352 (1.88), 10.042 (1.98). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
3% | With tris-(dibenzylideneacetone)dipalladium(0); palladium diacetate; caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; XPhos; In 1,4-dioxane; at 100.0℃; for 2.0h;Inert atmosphere; | To a solution of (cis)-6?-bromo-4-hydroxy-8?-methyl-4-(trifluoromethyl)-2?H-spiro[cyclohexane- 1,3?-imidazo[1,5-a]pyridine]-1?,5?-dione (prepared according to example 127b, 100 mg, 253 pmol) and <strong>[1190320-08-1]6-fluoroquinazolin-4-amine</strong> (GAS 1190320-08-1, 45.4 mg, 278 pmol) in 1,4-dioxane (10 mL) was added cesium carbonate (247 mg, 759 pmol) and the mixture was degassed and purged with argon several times. 4,5-Bis(diphenylphosphino)-9,9- dimethylxanthene (15.7 mg, 27.1 pmol), 2-(dicyclohexyl-phosphino)-2,4,6- triisopropylbiphenyl (12.9 mg, 27.1 pmol), palladium(ll)acetate (6.08 mg, 27.1 pmol) and tris(dibenzylideneacetone)dipalladium(0) (24.8 mg, 27.1 pmol) were added and the mixturewas stirred at 1 00cC for 2 hours. The mixture was concentrated and the residue purified by flash chromatography (Biotage SNAP cartridge silica 25 g, ethanol: dichloromethane). The isolated product was taken up in ethanol and stirred at RT. The solid was filtered off under vacuo, taken up in dichloromethane/ethanol again and stirred at RT. The solid was filtered off under vacuo and dried to give 4 mg (3% yield) of the title compound.LG-MS: m/z = 478.5 [M÷H].1H-NMR (400 MHz, DMSO-d6) 6 [ppm]= 1.232 (2.49), 1.360 (1.55), 1.427 (6.02), 1.458(6.11), 1.818 (5.42), 1.853 (6.88), 1.937 (4.47), 1 .964 (6.11), 1.997 (2.92), 2.326 (5.33),2.381 (8.86), 2.668 (5.33), 3.440 (3.78), 3.466 (5.68), 3.499 (3.18), 5.758 (6.37), 5.991(3.10), 6.008 (12.99), 7.830 (2.41), 7.852 (4.73), 7.868 (3.18), 7.935 (5.33), 7.949 (5.42),7.958 (4.22), 7.971 (3.27), 8.030 (2.92), 8.150 (4.47), 8.168 (4.73), 8.615 (1.55), 8.643(15.66), 8.797 (16.00), 9.351 (10.67), 10.469 (9.81), 10.605 (1.72). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | With tris-(dibenzylideneacetone)dipalladium(0); palladium diacetate; caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; XPhos; In 1,4-dioxane; at 100.0℃; for 2.0h;Inert atmosphere; | To a solution of 6?-bromo-8?-methyl-2?H-spiro[cyclobutane-1 ,3?-imidazo[l ,5-a]pyridine]-1 ?5?- dione (prepared according to example 146a, 100 mg, 353 pmol) and 6-fluoroquinazolin-4- amine (GAS 1190320-08-1, 63.4 mg, 389 pmol) in 1 ,4-dioxane (7.0 mL) was added cesium carbonate (345 mg, 1 .06 mmol) and the mixture was degassed and purged with argon several times. 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (21 .9 mg, 37.8 pmol), 2-(dicyclohexyl-phosphino)-2,4, 6-triisopropylbiphenyl (18.0 mg, 37.8 pmol), palladium(ll)acetate (8.48 mg, 37.8 pmol) and tris(dibenzylideneacetone)dipalladium(0) (34.6 mg, 37.8 pmol) were added and the mixture was stirred at 100cC for 2 hours. The mixture was concentrated and the residue purified by flash chromatography (Biotage SNAP cartridge silica 25 g, ethanol: dichloromethane). The isolated product was taken up inmethanol and stirred at RT. The solid was filtered off under vacuo and dried to give 66.0 mg (49 % yield) of the title compound.LG-MS: m/z = 366.5 [M÷H].1H-NMR (400 MHz, DMSO-d6) 6 [ppm]= 1.929 (0.53), 1.951 (0.59), 2.146 (0.57), 2.159 (0.57), 2.172 (0.53), 2.327 (1.55), 2.331 (1.49), 2.342 (0.77), 2.364 (1.28), 2.377 (1.06),2.388 (0.80), 2.401 (0.69), 2.470 (16.00), 2.665 (0.86), 2.669 (1.12), 2.673 (0.84), 3.404 (0.65), 3.429 (1.24), 3.456 (1.12), 3.482 (0.55), 7.825 (0.49), 7.832 (0.57), 7.848 (1.06), 7.855 (1.16), 7.869 (0.77), 7.875 (0.82), 7.935 (1.35), 7.948 (1.39), 7.958 (1.00), 7.972(0.86), 8.179 (1.08), 8.186 (1.14), 8.203 (1.12), 8.210 (1.06), 8.610 (4.59), 8.789 (4.79), 9.399 (2.65), 10.207 (2.41). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
37% | With tris-(dibenzylideneacetone)dipalladium(0); palladium diacetate; caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; XPhos; In 1,4-dioxane; at 100.0℃; for 2.0h;Inert atmosphere; | To a solution of 6-bromo-8-methyl-2H-spiro[imidazo[1 ,5-a]pyridine-3,3?-thietane]-l ,5-dione(prepared according to example 173a, 100 mg, 332 pmol) and <strong>[1190320-08-1]6-fluoroquinazolin-4-amine</strong>(GAS 1190320-08-1, 59.6 mg, 365 pmol) in 1 ,4-dioxane (6.6 mL) was added cesiumcarbonate (325 mg, 996 pmol) and the mixture was degassed and purged with argon severaltimes. 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (20.6 mg, 35.5 pmol), 2-(dicyclohexyl-phosphino)-2,4, 6-triisopropylbiphenyl (16.9 mg, 35.5 pmol),palladium(ll)acetate (7.98 mg, 35.5 pmol) and tris(dibenzylideneacetone)dipalladium(0) (32.5 mg, 35.5 pmol) were added and the mixture was stirred at 100cC for 2 hours. The mixture was concentrated and the residue purified by flash chromatography (Biotage SNAP cartridge silica 25 g, ethanol: dichloromethane). The isolated product was taken up in ethanol and stirred at RT. The solid was filtered off under vacuo and dried to give 50.0 mg (37%yield) of the title compound.LC-MS: m/z = 384.2 [M÷H].1H-NMR (400 MHz, DMSO-d6) 6 [ppm]= 1.035 (0.41), 1.052 (0.83), 1.070 (0.44), 2.323(0.59), 2.327 (0.82), 2.332 (0.68), 2.454 (16.00), 2.522 (1.84), 2.665 (0.57), 2.669 (0.77),2.673 (0.58), 3.308 (4.03), 4.688 (4.06), 4.714 (4.09), 5.758 (0.40), 7.832 (0.61), 7.839(0.72), 7.855 (1.31), 7.861 (1.44), 7.877 (0.95), 7.883 (1.06), 7.941 (1.74), 7.955 (1.77),7.964 (1.24), 7.977 (1.13), 8.215 (1.30), 8.222 (1.37), 8.239 (1.34), 8.246 (1.31), 8.609 (5.84), 8.796 (6.05), 9.413 (3.39), 10.774 (3.27). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With tris-(dibenzylideneacetone)dipalladium(0); palladium diacetate; caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; XPhos; In 1,4-dioxane; at 100.0℃; for 2.0h;Inert atmosphere; | To a solution of (cis)-6?-bromo-4-hydroxy-8?-methyl-4-(pentafluoroethyl)-2? Hspiro[cyclohexane-1 ,3?-imidazo[l ,5-a]pyridine]-1 ?,S?-dione (prepared according to example191 b, 100 mg, 225 pmol) and <strong>[1190320-08-1]6-fluoroquinazolin-4-amine</strong> (GAS 1190320-08-1, 40.3 mg,247 pmol) in 1 ,4-dioxane (9 mL) was added cesium carbonate (220 mg, 674 pmol) and the mixture was degassed and purged with argon several times. 4,5-Bis(diphenylphosphino)-9,9- dimethylxanthene (13.9 mg, 24.0 pmol), 2-(dicyclohexyl-phosphino)-2,4,6- triisopropylbiphenyl (11 .5 mg, 24.0 pmol), palladium(ll)acetate (5.40 mg, 24.0 pmol) andtris(dibenzylideneacetone)dipalladium(0) (22.0 mg, 24.0 pmol) were added and the mixture was stirred at 1000 for 2 hours. The mixture was filtered, concentrated and the residue purified by flash chromatography (Biotage SNAP cartridge silica 25 g, ethanol:dichloromethane). The isolated product was taken up in ethanol and stirred at RT. The solid was filtered off under vacuo and dried to give 68 mg (55% yield) of the title compound.LG-MS: m/z = 528.1 [M÷H].1H-NMR (400 MHz, DMSO-d6) 6 [ppm]= 1.231 (0.92), 1.440 (3.58), 1.471 (3.62), 1.905(2.66), 1 .934 (4.08), 1.973 (2.48), 2.001 (3.07), 2.034 (1.24), 2.332 (1 .88), 2.336 (0.83),2.371 (0.69), 2.518 (12.61), 2.523 (7.43), 2.539 (0.96), 2.673 (1.97), 2.678 (0.87), 3.458(1.60), 3.468 (1.83), 3.490 (3.16), 3.502 (2.98), 3.523 (1.79), 3.534 (1.38), 6.115 (10.54),7.823 (1 .51), 7.829 (1.79), 7.845 (2.93), 7.852 (3.35), 7.867 (2.29), 7.873 (2.57), 7.934(4.03), 7.948 (4.08), 7.957 (2.98), 7.971 (2.70), 8.130 (3.07), 8.137 (3.26), 8.154 (3.21), 8.161 (3.12), 8.634 (14.72), 8.795 (16.00), 9.351 (7.79), 10.487 (7.06). |
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