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Type | HazMat fee for 500 gram (Estimated) |
Excepted Quantity | USD 0.00 |
Limited Quantity | USD 15-60 |
Inaccessible (Haz class 6.1), Domestic | USD 80+ |
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Accessible (Haz class 3, 4, 5 or 8), International | USD 200+ |
Structure of 95-00-1
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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. : | 95-00-1 |
Formula : | C7H7Cl2N |
M.W : | 176.04 |
SMILES Code : | NCC1=C(Cl)C=C(Cl)C=C1 |
MDL No. : | MFCD00008109 |
InChI Key : | SJUKJZSTBBSGHF-UHFFFAOYSA-N |
Pubchem ID : | 1485 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H314 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Class: | 8 |
UN#: | 2735 |
Packing Group: | Ⅲ |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 44.14 |
TPSA ? Topological Polar Surface Area: Calculated from |
26.02 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.05 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.29 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.3 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.72 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.72 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.42 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.75 |
Solubility | 0.311 mg/ml ; 0.00177 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.47 |
Solubility | 0.591 mg/ml ; 0.00336 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.67 |
Solubility | 0.0375 mg/ml ; 0.000213 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 |
-5.75 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 |
2.0 |
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) |
1.21 |
* 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 |
---|---|---|
at 100℃; for 0.0833333h; | To 2.70 g of the oil, 2,4-dichlorobenzylamine (3.52 g) was added and the mixture was heated for at 100 C. for 5 min.. After cooling, the residue was washed with water (50 ml) and 2-propanol (50 ml) and dried to give the objective compound (3.10 g) as white crystals. 1H-NMR(DMSO-d6, delta ppm): 3.99(3H, s), 5.26(2H, s), 7.24-7.27(2H, m), 7.42 (1H, d, J=8.4 Hz), 7.44(1H, d, J=2.2 Hz), 8.12(1H, dd, J=8. 3 and 1.7 Hz), 8.25(1H, s), 8.35(1H, d, 8.4 Hz), 8.39(1H, d, 1.4 Hz) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Add sodium triacetoxyborohydride (156 mg, 0.73 mmol) to a mixture of 3-fluoro- 4-oxopyrrolidine-l-carboxylic acid tert-butyl ester (100 mg, 0.5 mmol) and 2,4- dichlorobenzylamine (65 muL, 0.5 mmol) in 1,2-dichloroethane (1.5 mL), followed by 2 drops of glacial acetic acid and stir overnight at room temperature. Pour the crude mixture into 2 N sodium hydroxide and extract with ethyl acetate, wash with water, dry (magnesium sulfate), concentrate and chromatograph on silica gel to give 3 -(2,4- dichlorobenzylamino)-4-fluoropyrrolidine-l-carboxylic acid tert-butyl ester (40 mg, 20%). 1H NMR (300 MHz, CDCl3) delta 7.36-7.44 (2H, m), 7.20-7.28 (IH, m), 5.03 (IH, d, J = 54.07 Hz)5 3.21-3.95 (6H, m), 2.99-3.15 (IH, m), 1.45 (9H5 s), MS (ES): m/z = 363 [M+]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
(2) Phosphorous oxychloride(41.45 g) was added to 6-nitro-1H-quinazolin-2,4-dione(3.0 g) and the mixture was stirred under reflux overnight. The reaction solution was concentrated, toluene was added to the residue and it was concentrated again. Chloroform was added to the residue, the precipitate was filtered, and water was added to the filtrate and it was separated. The organic layer was dried and the solvent was concentrated. Acetonitrile(50 mL) was added to the residue and the mixture was cooled to 0C, a solution of 2,4-dichlorobenzylamine(1.06 g) in acetonitrile(20 mL) was added dropwise. After stirring at 0C for 15 minutes, chloroform and water was added to the reaction solution. The organic layer was separated , dried and the solvent was concentrated. Diisopropyl ether was added to the residue, the precipitate was filtered and dried to give (2-chloro-6-nitro-quinazolin-4-yl)-(2,4-dichlorobenzyl)-amine(832 mg) as a yellow powder. APCI-MS(m/e):383/385[M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | To a suspension of 5-Formyl- 2- thiophenecarboxylic acid (2 g, 12.81 mmol) in 50 ml dichloromethane at 0°C, 1-Chlor-N,N,2-trimethylpropinylamin (1.88 g, 14.1 mmol) was added. The mixture was stirred 5 min at 0°C and then was allowed to reach RT and stirred at this temperature for 15 min. To the obtained clear solution, a solution of 2,4-dichlorobenzylamine (2.5 g, 14.1 mmol) and triethylamine (19.2 mmol) in 10 ml dichloromethane were added and the reaction was stirred at RT overnight. The mixture was diluted with dichloromethane and washed with aqueous HCl (0.25 M). The organic layer was dried, filtered off and concentrated under reduced pressure. The obtained residue- 5-Formyl-thiophene-2-carboxylic acid 2,4-dichloro-benzylamide (Intermediate 7)- (3.3g, 82percent) was used in the next step without further purification. 1 H NMR (DMSO-d6, 500 MHz) delta ppm 9.9 (s, 1 H), 9.41 (t, 1 H), 8.07 (d, 1 H), 7.98 (d, 1 H), 7.53 (s, 1 H), 7.49-7.35 (m, 2H), 4.52 (d, 2H). LC/MS (Method 2) Rt = 1.73 min; detected mass: m/z = 360.12 ([M+H]+). | |
82% | Intermediate 7: <strong>[4565-31-5]5-formyl-thiophene-2-carboxylic acid</strong> 2,4-dichlorobenzylamide To a suspension of 5-Formyl- 2- thiophenecarboxylic acid (2 g, 12.81 mmol) in 50 ml dichloromethane at 0°C, 1 -Chlor-N,N,2-trimethylpropinylamin (1 .88 g, 14.1 mmol) was added. The mixture was stirred 5 min at 0°C and then was allowed to reach RT and stirred at this temperature for 15 min. To the obtained clear solution, a solution of 2,4- dichlorobenzylamine (2.5 g, 14.1 mmol) and triethylamine (19.2 mmol) in 10 ml dichloromethane were added and the reaction was stirred at RT overnight. The mixture was diluted with dichloromethane and washed with aqueous HCI (0.25 M). The organic layer was dried, filtered off and concentrated under reduced pressure. The obtained residue- 5-Formyl-thiophene-2-carboxylic acid 2,4-dichloro-benzylamide (Intermediate 7)- (3.3g, 82percent) was used in the next step without further purification. 1 H NMR (DMSO-d6, 500 MHz) delta ppm 9.9 (s, 1 H), 9.41 (t, 1 H), 8.07 (d, 1 H), 7.98 (d, 1 H), 7.53 (s, 1 H), 7.49-7.35 (m, 2H), 4.52 (d, 2H). LC/MS ( Method 2) Rt = 1 .73 min;detected mass: m/z = 360.12 ([M+H]+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In acetonitrile; at 20℃; | General procedure: <strong>[97-08-5]4-Chloro-3-nitrobenzenesulfonyl chloride</strong> (1 equiv.) anddifferent amines (2 equiv.) were added to a 50 mL roundbottomedflask and dissolved in acetonitrile (25 mL). Thecontents were then stirred for 1-2 h at room temperature.Afterward, the solvent was removed under vacuum andthe product was washed with a dilute solution (5 %) ofNaHCO3 and filtered. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 24h; | A mixture of <strong>[34622-39-4](S)-6-oxopiperidine-2-carboxylic acid</strong> (1.00 g, 6.99 mmol), 2,4-dichlorobenzylamine (1.48 g, 8.38 mmol) and 3-[(ethylimino)methylene]amino}-N,N-dimethylpropan-1-aminiumchloride (EDCI) (1.61 g, 8.38 mmol), in CH2Cl2 was stirred at r.t. for 24 h. Solvents were evaporated and the mixture was solved in EtOH (40 mL), then Et2O was added (60 mL). The desired product crystalized over night. It was filtered to give a white solid in 62percent yield (1.30 g, 4.32 mmol). mp (EtOH/Et2O) 142-144 °C; TLC Rf (CH2Cl2/MeOH: 96/4) 0.3; 1H NMR (DMSO[d6], 400 MHz): delta ppm 1.56-1.81(m, 3H, CH2CH2CH2CH), 1.86-1.96 (m, 1H, CH2CH2CH2CH), 2.15 (t, J=6.8 Hz, 2H, CH2CH2CH2CH), 3.95 (dd, J= 5.9, 3.0 Hz, 1H,CH2CH2CH2CH), 4.28 (dd, J = 15.8, 5.6 Hz, 1H, NHCH2), 4.37 (dd, J = 15.8, 5.6 Hz, 1H, NHCH2), 7.38 (d, J = 8.3 Hz, 1H, ArH), 7.42 (dd, J = 8.3, 2.1 Hz, 1H, ArH), 7.57 (br d, J = 2.5 Hz, 1H, NHCH), 7.60 (d,J= 2.1 Hz, 1H, ArH), 8.52 (br t, J = 5.8 Hz, 1H, NHCH2); 13C NMR(DMSO[d6],100 MHz): delta ppm 18.9 (CH2), 26.4 (CH2), 31.7 (CH2), 40.2 (CH2), 55.4 (CH), 127.7 (CH), 128.9 (CH), 130.6 (CH), 132.6 (C), 133.3 (C), 135.9 (C), 170.9 (CH), 172.7 (C). Anal. Calcd for C13H14Cl2N2O2: C, 51.85; H, 4.69; N, 9.30. Found: C, 51.82; H, 4.70; N, 9.29percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
29% | With copper diacetate; palladium diacetate; 1,8-diazabicyclo[5.4.0]undec-7-ene; In 1,4-dioxane; at 95℃; | General procedure: The reaction was performed in a double-chamber system [67,68]. Amine/amines, Pd(OAc)2(0.05 equiv.) and Cu(OAc)2 (0.5 equiv.) were added to the reaction chamber and dissolved in1,4-dioxane (2 mL). In the CO-chamber was Mo(CO)6 (200 mg) dissolved in 1,4-dioxane (2 mL).After capping of the system, 1,8-diazabicyclo[5.4.0]undec-7-ene was added to the CO-chamber.The double-chamber system was positioned in a Dry-Syn heating block and heated to 95 C. Aftercompletion of the reaction, the reaction mixture was filtered through a short silica plug before flashcolumn chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With PdCl2(xantphos); In tetrahydrofuran; at 120℃; for 0.166667h;Sealed tube; | General procedure: Pd(Xantphos)Cl2 (4 mol) and amine/amines (30 mol) were added to an oven-dried, conicalglass vial followed by freshly distilled tetrahydrofuran (400 L). [11C]CO was transferred to the cappedreaction vial and the radioactivity was measured to determine the starting amount of [11C]CO. Thereaction was heated at 120 C for 10 min. When finished, the radioactivity was measured to confirm thatno radioactive material had escaped during heating. The vial was purged with N2 to remove unreacted[11C]CO and, possibly, volatile labelled compounds formed during the reaction. The radioactivity wasmeasured after the purge followed by either analytical HPLC for product selectivity determination orsemi-preparative HPLC purification for 11C-labelled product isolation. Purification was performedusing either column C1 = Phenomenex Kinetex C18 (5 m, 150 10.0 mm) column, C2 = Reprosil-PurBasic C18 (5 m, 150 10.0 mm) column or C3 = Gemini NX C18 (5 m, 250 10.0 mm) columnwith ammonium formate buffer 50 mM (pH 3.5) (A) and acetonitrile (B) as eluents. Run time was20 min with flow 5 mL/min followed by flushing the column with 100% B. After isolation and afinal radioactivity measurement of the 11C-labelled product, an aliquot was analysed to determineradiochemical purity and the identity of the 11C-labelled product was confirmed using the isotopicallyunmodified product as reference. The analytical method was the same for all compounds, 10-90%acetonitrile in 10 min (flow 2 mL/min). Molar activity determinations were based on a calibrationcurve, constructed with isotopically unmodified 20. For full definitions and calculations, see thesupporting materials. |
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