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Structure of 10320-42-0
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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. : | 10320-42-0 |
Formula : | C4H2ClN3O2 |
M.W : | 159.53 |
SMILES Code : | C1=C(C=NC(=N1)Cl)[N+]([O-])=O |
MDL No. : | MFCD04117995 |
InChI Key : | OFCBNMYNAHUDGE-UHFFFAOYSA-N |
Pubchem ID : | 82544 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H302-H315-H317-H318-H335 |
Precautionary Statements: | P261-P264-P270-P271-P272-P280-P301+P312+P330-P302+P352-P304+P340+P312-P305+P351+P338+P310-P333+P313-P403+P233-P405-P501 |
Class: | 9 |
UN#: | 3335 |
Packing Group: | Ⅲ |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 35.86 |
TPSA ? Topological Polar Surface Area: Calculated from |
71.6 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.94 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.99 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.04 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.94 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.41 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.32 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.83 |
Solubility | 2.36 mg/ml ; 0.0148 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.08 |
Solubility | 1.32 mg/ml ; 0.00828 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.64 |
Solubility | 3.67 mg/ml ; 0.023 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 |
-6.57 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 |
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) |
1.93 |
* 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 |
---|---|---|
75% | In methanol; for 1h;Reflux; | Example 40Synthesis of 4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-N-(2-methoxy-5-pyrimidinyl)-6-(4-morpholinyl)-1,3,5-triazin-2-amineThe compound was synthesized according to Method A.To a solution of sodium methoxide (0.090 g of sodium) in MeOH (12 mL) was added 0.486 g (3.03 mmol) of 2-chloro-5-nitropyrimidine, and the mixture was heated under reflux for 1 hr. After cooling, the mixture was concentrated in vacuo, extracted with EtOAc, and washed with water. The aqueous layer was extracted with CHCl3 and the combined organic layers were dried (Na2SO4), and concentrated, to give 0.347 g (75% yield) of 2-methoxy-5-nitropyrimidine as a yellow powder: 1H NMR (CDCl3) delta9.31 (s, 2H), 4.17 (s, 3H); LCMS (APCI+) m/z: 156 (MH+, 100%).To 0.342 g (2.20 mmol) of the above nitro compound in MeOH (20 mL) was added 0.30 g of 10% Pd/C and the mixture was stirred under hydrogen (25 in/Hg) for 18 hrs. The reaction mixture was filtered through celite, and concentrated, to give 0.274 g (100% yield) of 5-amino-2-methoxypyrimidine as a colorless oil: 1H NMR (DMSO-d6) delta 8.05 (s, 2H), 3.94 (s, 3H); LCMS (APCI+) m/z: 126 (MH+, 100%).To 0.274 g (2.19 mmol) of the above amino compound in THF (3 mL) was added 1.25 mL of NaHMDS (2 M solution in THF) and the mixture was stirred for 10 min. A solution of 0.31 g (0.78 mmol) of 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazole in THF (5 mL) was added and the resulting mixture was stirred for 90 min. The reaction mixture was neutralized with acetic acid, diluted with water, and extracted with EtOAc. The organic layer was washed with water and aq. NH3, dried, and concentrated. Recrystallization from EtOH/CH2Cl2 gave 0.098 g (26% yield) of 4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-N-(2-methoxy-5-pyrimidinyl)-6-(4-morpholinyl)-1,3,5-triazin-2-amine: mp 255-258 C.; 1H NMR (DMSO-d6) 810.07 (s, 1H), 8.88-8.74 (m, 2H), 8.15-7.42 (m, 3H), 6.97 (d, J=8.0 Hz, 1H), 3.98 (s, 3H), 3.93 (s, 3H), 3.82-3.72 (m, 8H); Anal. Calcd. for C21H21F2N6O3: C, 52.0; H, 4.4; N, 26.0. Found: C, 52.1; H, 4.5; N, 26.0%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N,N-dimethyl-formamide; at 20.0℃; for 2.0h; | Intermediate 162 To a solution of 4-bromo-3-[(trifluoromethyl)oxy]phenol (257 mg, 1.0 mmol) in dry DMF (4 mL) potassium carbonate (276 mg, 2 mmol) and then 2-chloro-5-nitropyrimidine (319 mg, 2.0 mmol) were added and the reaction mixture was stirred for 2 hours at r.t. The reaction was quenched with water (1 mL), diluted with brine (5 mL) and extracted with ethyl acetate (2x15mL). The organic layer was dried (Na2S04), filtered and evaporated to give crude 2-({4-bromo-3- [(trifluoromethyl)oxy]phenyl}oxy)-5-nitropyrimidine. This crude was dissolved in THF/water (2: 1 ) (6 mL) and Iron (279 mg, 5 mmol) and NH4CI (267,5 mg, 5 mmol) were added and the reaction mixture was stirred overnight at r.t. The solid was filtered off and the solution was diluted with an aqueous saturated solution of NaHC03 (5 mL) and extracted with ethyl acetate (2x20mL). The organic layer was dried (Na2S04), filtered and evaporated and the residue was purified by flash chromatography on silica gel (SNAP 25 g) eluting from 75:25 to 40:60 cyclohexane/ethyl acetate to afford the title compound (280 mg) as light yellow solid.H-NMR (400 MHz, DMSO-c/6): δ ppm 8.00 (2H, s), 7.81 (1 H, d), 7.34 - 7.40 (1 H, m), 7.14 (1 H, dd), 5.37 (2H, br. s.); UPLCjpqc: 1.02 min, 350 [M]+ Br pattern. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); XPhos; In 1,4-dioxane; at 85℃; for 12h; | Step A: tert-butyl-2-(5-nitropyrimidin-2-yl)-2,9-diazaspiro[5 .Slundecane-9-carboxylate: Astirred solution of 2-chloro-5-nitropyrimidine (0.1 g, 0.6 mmol), <strong>[1023595-19-8]tert-butyl 2,9-diazaspiro[5.5]undecane-9-carboxylate</strong> (0.1 g, 0.6 mmol), Pd2dba3 (0.02 g, 0.02 mmol), XPhos (0.04 g, 0.09 mmol), and K3P04(0.2 g, 1.1 mmol) in dioxane (17 mL) were heated to 85C for 12 h. The solution was diluted with H20 and stirred vigorously. The organic layer was removed, dried over Mg504, filtered, concentrated and purified using a 50 g Biotage SNAP cartridge (10-60%EtOAc:hexanes). LCMS: m/z 378.07 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60.37% | Synthesis of compound 114.2. A solution of Malonic ester (5.2g, 30.0mmol, 1.2eq.) in THF (60mL) was cooled at 0°C and NaH (60percent in oil) (2.3g, 57.0mmol, 2.3 eq) was added slowly at 0°C. Reaction mixture was stirred for 30 minutes at room temperature. A solution of 114.1 (4.0g, 25.0 mmol, l .Oeq) in THF (60mL), was added slowly and reaction mixture was stirred for 30 min at 0-5°C. After completion of the reaction, mixture was poured into cold water and extracted using EtOAc (50ml x2). Organic layer was dried over sodium sulfate and concentrated under reduced pressure. Crude was purified by flash column chromatography to afford 114.2 5.5g, 60.37percent). MS (ES): m/z 297.3 [M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | In acetonitrile;Inert atmosphere; | The first step: a vacuum 50mL reaction bottle was vacuumed three times, then added <strong>[26807-73-8]1-benzyl-1H-indole-5-amine</strong> (222mg, 1.0mmol, 1.0equiv) to the reaction jar, added 10.0 mL of the dried acetonitrile was stirred until <strong>[26807-73-8]1-benzyl-1H-indole-5-amine</strong> was completely dissolved, and then 2-chloro-5-nitropyrimidine (0.1593 g, 1.0 mmol, was added to the reaction flask).1.0equiv). The entire mixture was reacted under nitrogen pressure for 4-5 hours. The reaction is detected by TLC to detect the progress of the reaction.The reaction can be stopped by the complete reaction of the aniline. The experimental treatment is to drain the solution in the reaction; the reaction is carried out with ethyl acetate.The solute in the jar was dissolved and transferred to a 100 mL round bottom flask. 2 mL (200-300 mesh) of silicon was added to the round bottom flask.The gel was spin-dried (petroleum ether and ethyl acetate) over silica gel on a column. Wait until the intermediate product is pale yellow crystal 1-benzyl-N-(5-nitropyrimidinePyridin-2-yl)-1H-indole-5-amine (276 mg, 80% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87.4% | With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 20.0℃; for 0.5h; | 2-Chloro-5-Nitropyrimidine (87 mg, 0.55 mmol) was added to a solution (2R)-2-(3- fluorophenyl)pyrrolidine hydrochloride (100 mg, 0.50 mmol) in tetrahydrofuran (10 ml_). To this mixture was added diisopropylethylamine (0.4 ml_).The resulting reaction mixture was stirred at room temperature for 30 min. The reaction mixture was concentrated to dryness under reduced pressure. The crude product suspended in small amount of methanol, crystallisation occurs. Formed crystals was collected by filtration to give the title compound as a white solid. (125 mg, 87.4%). 1H NMR(300 MHz, Chloroform-d) d 9.13 (d, J = 3.3 Hz, 1H), 8.94 (d, J = 3.3 Hz, 1H), 7.32 - 7.21 (m, 1H), 6.98 - 6.87 (m, 2H), 6.86 - 6.77 (m, 1H), 5.44 -5.36 (m, 1H), 4.08 - 3.92 (m, 1H), 3.95 - 3.79 (m, 1H), 2.56 - 2.35 (m, 1H), 2.16 - 1.98 (m, 3H). LCMS : m/z 289.10 [M + H+]. |
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