Structure of 98276-57-4
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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. : | 98276-57-4 |
Formula : | C7H8N2O |
M.W : | 136.15 |
SMILES Code : | O=CC1=CC=C(N)C=C1N |
MDL No. : | MFCD02094162 |
InChI Key : | VMFJRVFZHAPENO-UHFFFAOYSA-N |
Pubchem ID : | 11147748 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 40.64 |
TPSA ? Topological Polar Surface Area: Calculated from |
69.11 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.68 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.57 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.68 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.18 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.55 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.53 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.42 |
Solubility | 5.16 mg/ml ; 0.0379 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.59 |
Solubility | 3.47 mg/ml ; 0.0255 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.6 |
Solubility | 3.44 mg/ml ; 0.0253 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 |
No |
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 |
-6.73 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 |
2.0 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 |
---|---|---|
With hydrogen; In ethyl acetate; at 30℃; under 750.075 Torr; for 18.0h;Schlenk technique;Catalytic behavior; | General procedure: The substrate (0.5 mmol), NiPd/MIL-101 catalyst (0.023g, Pd 0.2 mol%), and ethyl acetate (4 mL) were added to a Schlenk tube, and the mixture was vigorously stirred with an affixed hydrogenation balloon at room temperature. Following the reaction, the solid catalyst was removed from the solution by filtration and washed with ethyl acetate. The product yields were determined by gas chromatography-mass spectrometry (GC/MS, Shimadzu GCMS- QP5050A) with a 0.25 mm × 30 mDB-WAX capillary column. Parameters were as follows: initialoven temperature, 100 C, 1 min; ramp, 20 C/min; final temperature, 280 C; final time, 5 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; In ethanol; water; at 60℃; for 16.0h; | Reference Example 65 2-methyl-1,2,3,4-tetrahydrobenzo[b][1,6] naphthyridin-7-amine A solution of <strong>[98276-57-4]2,4-diaminobenzaldehyde</strong> (1.00 g, 7.34 mmol), 1-methyl-4-piperidinone (1.08 ml, 8.81 mmol) and 4N aqueous sodium hydroxide solution (11 ml) in ethanol (70 ml) was stirred at 60C for 16 hrs, and the solvent was evaporated under reduced pressure.. The residue was dissolved in ethyl acetate, washed with aqueous potassium carbonate solution and saturated brine, and dried over anhydrous sodium sulfate.. The obtained crude product was purified by NH-silica gel chromatography (elute solvent; ethyl acetate) and treated with ethyl acetate - isopropyl ether (1:5) to give the title compound (666 mg) as a powder.1H-NMR (DMSO-d6) delta: 2.37 (3H, s), 2.71 (2H, t, J = 6.0 Hz), 2.96 (2H, t, J = 6.0 Hz), 3.56 (2H, s), 5.58 (2H, br), 6.80 (1H, d, J = 2.1 Hz), 6.87 (1H, dd, J = 2.1, 8.4 Hz), 7.48 (1H, d, J = 8.4 Hz), 7.64 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With nitrogen; In water; acetic acid; ethyl acetate; | Method 1 2,4-Diaminobenzaldehyde To a nitrogen purged 5 liter 4-neck flask fitted with a condenser, mechanical stirrer, addition funnel, and temperature probe, was added 325 mesh iron dust, which can be obtained from Aldrich, Milwaukee, Wis. (220 g, 3.9 mol, 8 equiv), water (800 mL), and glacial acetic acid (5 mL). Over the next hour, some frothing occurred and the temperature rose to 28 C. In a separate container, 2,4-dinitrobenzaldehyde (97 g, 0.49 mol, 1 equiv) was dissolved in 1:1 glacial acetic acid/ethyl acetate (800 mL). 2,4-Dinitrobenzaldehyde can be purchased from Aldrich, Milwaukee, Wis. About 5 mL of the 2,4-dinitrobenzaldehyde solution was added dropwise to the iron mixture, which led to a dissipation of the frothing. The reaction mixture was warmed to 35 C. with a steam bath. Without further heating, the remaining dinitrobenzaldehyde solution was added at such a rate as to maintain the temperature below 50 C. The addition was completed after 6 hours. The reaction mixture was diluted with water (1 L) and diatomaceous earth (BNL Fine Chemicals and Reagents, Meriden, Conn.) was added (100 g). The reaction mixture was stirred an additional 3 hours at which point the temperature had dropped to 25 C. The solids were removed by filtration. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (3*400 mL). The extracts were then used to wash the solids from the initial filtration. The organic layers were combined and washed with water (400 mL) and saturated aqueous NaHCO3 (3*400 mL). The combined organic layers were dried over MgSO4 and Darco G-60 (activated charcoal; BNL Fine Chemicals and Reagents, Meriden, Conn.) (10 g). After filtration to remove the drying agents, the organic layers were concentrated in vacuo to a slurry and diluted with 1 L of hexanes. The precipitated solids were collected by suction filtration and dried in air to give 2,4-diaminobenzaldehyde (48 g, 71%) as a light yellow solid. 1H NMR (acetone-d6) delta5.48 (brs, 2H), 5.94 (d, 1H, J=1.9 Hz), 6.08 (dd, 1H, J=2.0, 8.6 Hz), 6.75 (br s, 2H), 7.20 (d, 1H, J=8.6 Hz), 9.51 (s, 1H). |
71% | With nitrogen; In water; acetic acid; ethyl acetate; | 2,4-Diaminobenzaldehyde To a nitrogen purged 5 liter 4-neck flask fitted with a condenser, mechanical stirrer, addition funnel, and temperature probe, was added 325 mesh iron dust, which can be obtained from Aldrich, Milwaukee, Wis. (220 g, 3.9 mol, 8 equiv), water (800 mL), and glacial acetic acid (5 mL). Over the next hour, some frothing occurred and the temperature rose to 28 C. In a separate container, 2,4-dinitrobenzaldehyde (97 g, 0.49 mol, 1 equiv) was dissolved in 1:1 glacial acetic acid/ethyl acetate (800 mL). 2,4-Dinitrobenzaldehyde can be purchased from Aldrich, Milwaukee, Wis. About 5 mL of the 2,4-dinitrobenzaldehyde solution was added dropwise to the iron mixture, which led to a dissipation of the frothing. The reaction mixture was warmed to 35 C with a steam bath. Without further heating, the remaining dinitrobenzaldehyde solution was added at such a rate as to maintain the temperature below 50 C. The addition was completed after 6 hours. The reaction mixture was diluted with water (1 L) and diatomaceous earth (BNL Fine Chemicals and Reagents, Meriden, Conn.) was added (100 g). The reaction mixture was stirred an additional 3 hours at which point the temperature had dropped to 25 C. The solids were removed by filtration. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (3*400 mL). The extracts were then used to wash the solids from the initial filtration. The organic layers were combined and washed with water (400 mL) and saturated aqueous NaHCO3 (3*400 mL). The combined organic layers were dried over MgSO4 and Darco G-60 (activated charcoal; BNL Fine Chemicals and Reagents, Meriden, Conn.) (10 g). After filtration to remove the drying agents, the organic layers were concentrated in vacuo to a slurry and diluted with 1 L of hexanes. The precipitated solids were collected by suction filtration and dried in air to give 2,4-diaminobenzaldehyde (48 g, 71%) as a light yellow solid. 1H NMR (acetone-d6) delta5.48 (br s, 2H), 5.94 (d, 1H, J=1.9 Hz), 6.08 (dd, 1H, J=2.0, 8.6 Hz), 6.75 (br s, 2H), 7.20 (d, 1H, J=8.6 Hz), 9.51 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | With sodium hydroxide; nitrogen; In tetrahydrofuran; dichloromethane; | Preparation 6 4'-Trifluoromethyl-biphenyl-2-carboxylic acid (3-amino-4-formyl-phenyl)-amide To a nitrogen purged 12 liter 3-neck flask fitted with a mechanical stirrer and temperature probe was added THF (4.3 L) and <strong>[98276-57-4]2,4-diaminobenzaldehyde</strong> (50 g, 0.37 mol, 1 equiv). After cooling the solution to -70 C. (dry ice/acetone bath), poly(4-vinylpyridine), which can be obtained form Aldrich, Milwaukee, Wis., 25% cross-linked, (210 g) was added. A solution of 4'-trifluoromethyl-biphenyl-2-carbonyl chloride (105 g, 0.37 mol, 1 equiv) in THF (1 L) was added at such a rate as to maintain the temperature below -60 C. The light orange reaction mixture was allowed to warm to room temperature over 4 hours to give a dark red reaction mixture. (HPLC analysis showed an 18:1 mixture of mono- (retention time (rt)=4.8 min) to di- (rt=3.1 min) acylated products along with 5% residual starting material (rt=18.8 min), (Zorbax SIL (150 mm) from Agilent Technologies, Palo Alto, Calif. 2 mL/min 90:10 hexanes/isopropanol, 0.1% diethylamine, 250 nm, 40 C.). The reaction was quenched with 1 N NaOH (450 mL) and allowed to stir overnight at 25 C. The reaction mixture was filtered and the solids were washed with ethyl acetate (5*200 mL) and the combined organic layers were concentrated in vacuo to give a brown oil. The oil was dissolved in CH2Cl2 (1.5 L) and silica gel (EM Science, Gibbstown, N.J., 230-400 mesh or 0.04-0.06 mm particle size) (410 g) and Darco G-60 (10 g, BNL Fine Chemicals and Reagents) were added. The slurry was stirred for 15 minutes and filtered. The silica was washed with CH2Cl2 (5*200 mL). The combined organic layers were concentrated in vacuo and the methylene chloride was displaced with 1:1 hexanes/diisopropylether. The precipitated product was collected by suction filtration and dried in air to give 4'-trifluoromethyl-biphenyl-2-carboxylic acid (3-amino-4-formyl-phenyl)-amide (40 g, 30%, 43:1 mono:bis acylated by HPLC) as a light yellow solid. MS (APCI) 385 (M+1)+; 383 (M-1)- 1H NMR (DMSO-d6) delta6.65 (dd, 1H, J=1.7, 8.7 Hz), 7.15 (br s, 2H), 7.25 (s, 1H), 7.38 (d, 1H, J=8.7 Hz), 7.46-7.68 (m, 6H), 7.74 (d, 2H, J=8.3 Hz), 9.57 (s, 1H), 10.51 (s, 1H). |
30% | With sodium hydroxide; nitrogen; In tetrahydrofuran; dichloromethane; | 4'-Trifluoromethyl-biphenyl-2-carboxylic acid (3-amino-4-formyl-phenyl)-amide To a nitrogen purged 12 liter 3-neck flask fitted with a mechanical stirrer and temperature probe was added THF (4.3 L) and <strong>[98276-57-4]2,4-diaminobenzaldehyde</strong> (50 g, 0.37 mol, 1 equiv). After cooling the solution to -70 C. (dry ice/acetone bath), poly(4-vinylpyridine), which can be obtained from Aldrich, Milwaukee, Wis., 25% cross-linked, (210 g) was added. A solution of 4'-trifluoromethyl-biphenyl-2-carbonyl chloride (105 g, 0.37 mol, 1 equiv) in THF (1 L) was added at such a rate as to maintain the temperature below -60 C. The light orange reaction mixture was allowed to warm to room temperature over 4 hours to give a dark red reaction mixture. (HPLC analysis showed an 18:1 mixture of mono- (retention time (rt)=4.8 min) to di- (rt=3.1 min) acylated products along with 5% residual starting material (rt=18.8 min), (Zorbax SlL (150 mm) from Agilent Technologies, Palo Alto, Calif. 2 mL/min 90:10 hexanes/isopropanol, 0.1% diethylamine, 250 nm, 40 C.). The reaction was quenched with 1 N NaOH (450 mL) and allowed to stir overnight at 25 C. The reaction mixture was filtered and the solids were washed with ethyl acetate (5*200 mL) and the combined organic layers were concentrated in vacuo to give a brown oil. The oil was dissolved in CH2Cl2 (1.5 L) and silica gel (EM Science, Gibbstown, N.J., 230-400 mesh or 0.04-0.06 mm particle size) (410 g) and Darco G-60 (10 g, BNL Fine Chemicals and Reagents) were added. The slurry was stirred for 15 minutes and filtered. The silica was washed with CH2Cl2 (5*200 mL). The combined organic layers were concentrated in vacuo and the methylene chloride was displaced with 1:1 hexanes/diisopropylether. The precipitated product was collected by suction filtration and dried in air to give 4'-trifluoromethyl-biphenyl-2-carboxylic acid (3-amino-4-formyl-phenyl)-amide (40 g, 30%, 43:1 mono:bis acylated by HPLC) as a light yellow solid. MS (APCI) 385 (M+1)+; 383 (M-1)- 1H NMR (DMSO-d6) delta6.65 (dd, 1H, J=1.7, 8.7 Hz), 7.15 (br s, 2H), 7.25 (s, 1H), 7.38 (d, 1H, J=8.7 Hz), 7.46-7.68 (m, 6H), 7.74 (d, 2H, J=8.3 Hz), 9.57 (s, 1H), 10.51 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Specific examples of formula (A) compounds are: ... calcium di-2,4-diaminobenzoate ammonium 2,4-diaminobenzoate trimethylammonium 2,4-diamineobenzoate tri-(2-hydroxyethyl)ammonium 2,4-diaminobenzoate 2,4-diaminobenzaldehyde 2,4-diaminobenzenesulfonic acid potassium 2,4-diaminobenzenesulfonate N,N-diisopropyl-p-phenylenediamine ... |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; In N,N-dimethyl-formamide; at 20℃; | To <strong>[98276-57-4]2,4-diaminobenzaldehyde</strong> (11.5 mg), NHS-dPEG4 biotin (QuantaBiodesign, cat No. 10200, 50mg) and DMAP (10.4 mg) was added 1.OmL DMF. The reaction mixture was stirred at room temperature until the reaction was complete, monitored by HPLC. The product was isolated by silica gel flash chromatography. MS (ESI+): 610.28 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To 2,2,5,5-tetramethyl-3-pyrrolin-l-oxyl-3-carboxylic acid (55.3mg), HBTU (102mg) and DIEA (105muL) were added 2.0 mL DMF. After stirred at room temperature for 30 minutes, <strong>[98276-57-4]2,4-diaminobenzaldehyde</strong> (40.8 mg) was added. The mixture was stirred at room temperature until the reaction was complete, monitored by HPLC. The title product was isolated by preparative HPLC. MS (ESI+): m/z 303.15 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | With potassium hydroxide; In toluene; for 16.0h;Reflux; | Synthesis method of THK-5075 Synthesis of THK-5075 A mixture of 73 (1.19 g, 8.74 mmol), 74 (1.06 ml, 8.74 mmol), potassium hydroxide (590 mg, 10.5 mmol) and toluene (40 ml) was heated at reflux for 16 hours. The reaction solution was allowed to return to room temperature, and water and an aqueous saturated ammonium chloride solution were added and the solution was extracted with ethyl acetate. Insolubles were removed by filtration with celite. The extraction liquid was washed with water and dried, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: n-hexane/ethyl acetate = 9/1, 2/1) and then recrystallized from ethyl acetate-n-hexane to obtain THK-5075 (737 mg, 35%) as pale yellow crystals. mp 160-161C, 1H NMR (500 MHz,DMSO-d6)delta 5.80 (2H,s), 6.96-7.00 (2H,m), 7.33 (2H,t,J=8.8Hz), 7.63 (1H,d,J=9.6Hz), 7.68 (1H,d,J=8.4Hz), 8.11 (1H,d,J=8.4Hz), 8.24 (2H,dd,J=9.0,5.5Hz) IR (Nujol) 3388, 1619, 1600 cm-1 APCI-MS m/z 239[M+H]+ |
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