Structure of 7126-38-7
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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. : | 7126-38-7 |
Formula : | C5H4N2 |
M.W : | 92.10 |
SMILES Code : | N#CC1=CNC=C1 |
MDL No. : | MFCD00967073 |
InChI Key : | PCYWMDGJYQAMCR-UHFFFAOYSA-N |
Pubchem ID : | 564206 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Num. heavy atoms | 7 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 25.51 |
TPSA ? Topological Polar Surface Area: Calculated from |
39.58 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.04 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.43 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.89 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.56 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.43 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.65 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.21 |
Solubility | 5.67 mg/ml ; 0.0616 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.83 |
Solubility | 13.7 mg/ml ; 0.148 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.6 |
Solubility | 2.31 mg/ml ; 0.0251 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) |
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 |
-6.56 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) |
1.34 |
* 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 N,N-dimethyl-formamide; | 3-Fluoro-4-(3-cyano-1-pyrrolyl)nitrobenzene <strong>[7126-38-7]3-Cyanopyrrole</strong> (3.6 g, 39.1 mmol, CE Loader et al, Can. J. Chem., 1981, 59, 2673) and 3,4-difluoronitrobenzene (6.5 g, 40.9 mmol) were dissolved in DMF (50 ml) and cooled in an ice-bath. The mixture was stirred and sodium hydride (60percent in oil, 1.6 g, 40 mmol) added over 20 minutes. After allowing the mixture to come to ambient temperature, it was heated to 65° for 1 hour. Solvent was evaporated, the residue triturated with water, and filtered. The crude solide was purified by flash chromatography on silica, eluding with dichloromethane. Relevant fractions were combined to give the title product (3.75 g), mp 117-119°. MS (ESP): 230 (MH-) for C11H6FN3O2 NMR (CDCl3) delta: 6.68 (s, 1H); 7.09 (m, 1H); 7.61 (overlapping m, 2H); 8.20 (overlapping m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bromine; In dichloromethane; chloroform; | EXAMPLE 12 Preparation of 2,4,5-Tribromo<strong>[7126-38-7]pyrrole-3-carbonitrile</strong> STR23 To a stirred mixture of 1.50 g (16.3 mmol) of <strong>[7126-38-7]pyrrole-3-carbonitrile</strong> in 20 mL of chloroform is added dropwise from an addition funnel a mixture of 2.5 mL (48.5 mmol) of bromine in 7.5 mL of chloroform over about 30 minutes. The temperature of the mixture rises to 38° C. and a gummy solid is formed which necessitates addition of additional chloroform (25 mL) and some warming to achieve good stirring. The mixture is stirred an additional 2 hours at room temperature and the solid product is collected by filtration and washed with chloroform. The collected solids amount to 4.55 g. Concentration of the filtrate affords another 0.58 g of product. The combined solids are slurried with boiling methylene chloride. On cooling, filtration gives 3.66 g of a pale orange powder, mp 253°-255° C. Anal. Calcd for C5 HBr3 N2: C, 18.26; H, 0.31; N, 8.52; Br, 72.91. Found: C, 18.28; H, 0.35; N, 8.52; Br, 72.74. | |
With bromine; In dichloromethane; chloroform; | EXAMPLE 18 Preparation of 2,4,5-Tribromo<strong>[7126-38-7]pyrrole-3-carbonitrile</strong> STR24 To a stirred mixture of 1.50 g (16.3 mmol) of <strong>[7126-38-7]pyrrole-3-carbonitrile</strong> in 20 mL of chloroform is added dropwise from an addition funnel a mixture of 2.5 mL (48.5 mmol) of bromine in 7.5 mL of chloroform over about 30 minutes. The temperature of the mixture rises to 38° C. and a gummy solid is formed which necessitates addition of additional chloroform (25 mL) and some warming to achieve good stirring. The mixture is stirred an additional 2 hours at room temperature and the solid product is collected by filtration and washed with chloroform. The collected solids amount to 4.55 g. Concentration of the filtrate affords another 0.58 g of product. The combined solids are slurtied with boiling methylene chloride. On cooling, filtration gives 3.66 g of a pale orange powder, mp 253°-255° C. Anal. Calcd for C5 HBr3 N2: C, 18.26; H, 0.31; N, 8.52; Br, 72.91, Found: C, 18.28; H, 0.35; N, 8.52; Br, 72.74. | |
With bromine; In dichloromethane; chloroform; | EXAMPLE 12 Preparation of 2,4,5-Tribromo<strong>[7126-38-7]pyrrole-3-carbonitrile</strong> STR26 To a stirred mixture of 1.50 g (16.3 mmol) of <strong>[7126-38-7]pyrrole-3-carbonitrile</strong> in 20 mL of chloroform is added dropwise from an addition funnel a mixture of 2.5 mL (48.5 mmol) of bromine in 7.5 mL of chloroform over about 30 minutes. The temperature of the mixture rises to 38° C. and a gummy solid is formed which necessitates addition of additional chloroform (25 mL) and some warming to achieve good stirring. The mixture is stirred an additional 2 hours at room temperature and the solid product is collected by filtration and washed with chloroform. The collected solids amount to 4.55 g. Concentration of the filtrate affords another 0.58 g of product. The combined solids are slurried with boiling methylene chloride. On cooling, filtration gives 3.66 g of a pale orange powder, mp 253°-255° C. Anal. Calcd for C5 HBr3 N2: C, 18.26; H, 0.31; N, 8.52; Br, 72.91 Found: C, 18.28; H, 0.35; N, 8.52; Br, 72.74. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2.23 g (70%) | With sulfuryl dichloride; In water; acetic acid; | EXAMPLE 11 Preparation of 2,4,5-Trichloro<strong>[7126-38-7]pyrrole-3-carbonitrile</strong> STR22 To a stirred mixture of 1.50 g (16.3 mmol) of <strong>[7126-38-7]pyrrole-3-carbonitrile</strong> in 50 mL of glacial acetic acid is added quickly dropwise 4.1 mL (51.0 mmol) of sulfuryl chloride by syringe through a rubber septum. With this addition the temperature of the reaction mixture rises from about 22° C. to 32° C. The mixture is stirred one and one-half hours and then diluted with 100 mL of water. The resulting solids are collected by filtration and washed with water. On drying, the yield is 2.23 g (70percent) of white solid, mp >300° C. |
2.23 g (70%) | With sulfuryl dichloride; In water; acetic acid; | EXAMPLE 17 Preparation of 2,4,5-Trichloro<strong>[7126-38-7]pyrrole-3-carbonitrile</strong> STR23 To a stirred mixture of 1.50 g (16.3 mmol) of <strong>[7126-38-7]pyrrole-3-carbonitrile</strong> in 50 mL of glacial acetic acid is added quickly dropwise 4.1 mL (51.0 mmo1) of sulfuryl chloride by syringe through a rubber septum. With this addition the temperature of the reaction mixture rises from about 22° C. to 32° C. The mixture is stirred one and one-half hours and then diluted with 100 mL of water. The resulting solids are collected by filtration and washed with water. On drying, the yield is 2.23 g (70percent) of white solid, mp >300° C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46.7% | With NaH; sodium ethanolate; In tetrahydrofuran; mineral oil; | EXAMPLE 4 Preparation of 2,4,5-Tribromo-1-ethoxymethyl)pyrrole-3-carbonitrile STR7 A mixture of a 60percent dispersion of NaH in mineral oil (1.22 g, 0.0304 mol NaH) in tetrahydrofuran is treated dropwise with a solution of 2,4,5-tribromopyrrole-3-carbonitrile (10.0 g, 0.0304 mol) in tetrahydrofuran at 20° C. to 30° C. over a 20 minute period, stirred for 30 minutes at ambient temperatures, treated with bromochloromethane (11.80 g, 0.0912 mol) and solid sodium ethoxide (6.2 g, 0.0912 mol), heated at reflux temperature for 4 hours, cooled to room temperature, concentrated in vacuo and diluted with water and ethyl acetate. The organic phase is washed with water and brine, dried (Na2 SO4) and concentrated in vacuo to give a residue which is purified by flash chromatography (silica gel; ethyl acetate/heptane) to give the title compound as a white solid, 5.4 g (46.7percent yield), mp 139° C. to 143° C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuryl dichloride; In tetrahydrofuran; dichloromethane; water; acetic acid; | EXAMPLE 11 Preparation of 2,4,5-Trichloro<strong>[7126-38-7]pyrrole-3-carbonitrile</strong> STR22 To a stirred mixture of 1.50 g (16.3 mmol) of <strong>[7126-38-7]pyrrole-3-carbonitrile</strong> in 50 mL of glacial acetic acid is added quickly dropwise 4.1 mL (51.0 mmol) of sulfuryl chloride by syringe through a rubber septum. With this addition the temperature of the reaction mixture rises from about 22° C. to 32° C. The mixture is stirred one and one-half hours and then diluted with carbonitrile in 20 mL of dry THF over a 15 minute period. After 15 minutes, 0.50 mL (8.03 mmol) of methyl iodide is added dropwise by syringe over 10 minutes. Solids are formed and after stirring for about 3 hours, the mixture is diluted with 100 mL of water. The cloudy mixture is extracted twice with ethyl acetate and the combined organic layers washed successively with dilute NaOH, water, and saturated salt solution. After drying over magnesium sulfate, the organic mixture is filtered and concentrated in vacuo to give 0.99 g of an off-white solid. Purification by chromatography on silica gel using methylene chloride affords 0.68 g of yellow-white solid which is slurried with hexane and recovered by filtration; mp 110°-114° C. Anal. Calcd for C6 H3 Cl3 N2: C, 34.40; H, 1.44; N, 13 38; Cl, 50.78. Found: C, 34.25; H, 1.50; N, 13.36; Cl, 50.88. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetra(n-butyl)ammonium hydroxide; In tetrahydrofuran; water; at 20℃; for 0.5h; | Reference Production Example 38 1-chloromethyl-3-cyano-1H-pyrole 670 mg of 3-cyano-1H-pyrole, 10 ml of tetrahydrofuran and 10 ml of formaldehyde 36 percent in water were mixed. 0.1 ml of tetrabutylammonium hydroxide 10 percent in water was added at room temperature, followed by stirring at room temperature for 30 minutes. The reaction mixture was poured into ice-water, and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure to obtain 1-hydroxymethyl-3-cyano-1H-pyrole. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: The example reported for derivatives 22/23 find general application for all the other N-linked heterocycles. Sodium hydride 60percent dispersed in mineral oil was added at 0 °C to a solution of 3-(trifluoromethyl)-1H-pyrazole in dry DMF. The mixture was stirred at this temperature for 15 min, then for an additional 5 min at room temperature. A solution of derivative 45 in dry DMF (2 ml) was then added and the mixture was stirred at 50 °C for 3 h 30 min. After cooling to RT, a saturated NH4Cl solution was added and the mixture was extracted with Et2O (2.x.). The organic phase was washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by Silica gel flash chromatography (gradient ethyl acetate in cyclohexane from 5 to 40percent) to give the intermediate BOC protected compound 22 and the intermediate BOC protected compound 23. |
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