Structure of 1279815-46-1
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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. : | 1279815-46-1 |
Formula : | C9H7BrN2 |
M.W : | 223.07 |
SMILES Code : | N#CC1(C2=CC(Br)=NC=C2)CC1 |
MDL No. : | MFCD20278074 |
InChI Key : | HKLRZPZCPJJBTP-UHFFFAOYSA-N |
Pubchem ID : | 71743245 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.33 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 48.84 |
TPSA ? Topological Polar Surface Area: Calculated from |
36.68 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.98 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.88 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.34 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.5 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.99 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.14 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.71 |
Solubility | 0.434 mg/ml ; 0.00194 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.27 |
Solubility | 1.19 mg/ml ; 0.00534 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.79 |
Solubility | 0.0363 mg/ml ; 0.000163 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 |
-6.33 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 |
0.0 |
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 |
1.0 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) |
1.97 |
* 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 sodium hydride; In diethyl ether; dimethyl sulfoxide; mineral oil; at 20℃; for 18.0h;Cooling with water bath; | A solution of (2-bromo-pyridin-4-yl)-acetonitrile (1.20 g, 6.09 mmol) and the 1,2- dibromoethane (0.663 mL, 7.61 mmol) in a mixture of dry Et20 (5 mL) and dry DMSO (1 mL) is added to a suspension of NaH (60% dispersion in mineral oil, 585 mg, 14.6 mmol) in dry DMSO (10 mL) while controlling the resulting exotherm by cooling in a water bath, and the resulting mixture is stirred at room temperature. After 18 hours, water (10 mL) and ethyl acetate (10 mL) are added, phases are separated and the aqueous layer is extracted with ethyl acetate (3 x 10 mL). The combined organic layers are washed with brine (30 mL) and dried over MgS04, filtered and concentrated. The residue is purified on Si02 eluting with a gradient of 0-60% ethyl acetate in heptane to afford l-(2-bromo-pyridin-4-yl)-cyclopropanecarbonitrile as a solid (ES+ m/z 223.36; 225.39). | |
With sodium hydride; In diethyl ether; dimethyl sulfoxide; mineral oil; at 20℃; for 18.0h; | A solution of (2-bromopyridin-4-yl)-acetonitrile (1.20 g, 6.09 mmol) and the 1,2- dibromoethane (0.663 mL, 7.61 mmol) in a mixture of anhydrous Et20 (5 mL) and anhydrous DMSO (1 mL) is added to a suspension of NaH (60% dispersion in mineral oil, 585 mg, 14.6 mmol) in anhydrous DMSO (10 mL) while controlling the resulting exotherm by cooling in a water bath, and the resulting mixture is stirred at room temperature. After 18 hours, water (10 mL) and EtOAc (10 mL) are added, phases are separated and the aqueous layer is extracted with EtOAc (3 x 10 mL). The combined organic layers are washed with brine (30 mL) and dried over MgS04, filtered and concentrated. The residue is purified by silica gel chromatography eluting with a gradient of 0-60% EtOAc in heptane to afford l-(2-bromopyridin-4-yl)- cyclopropanecarbonitrile as a solid. MS mJz 223 A, 225 A. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a solution of l-(2-bromo-pyridin-4-yl)-cyclopropanecarbonitrile (1.16 g, 5.20 mmol) in toluene (30 mL) is added DIBAL-H (10.4 mL, 1M in toluene) at -78C. The mixture is stirred 1 hour at -78C and warmed to room temperature. After 1 hour, ethyl acetate (30 mL) is added, followed by 1M aqueous solution of H2S04 (30 mL). Phases are separated and the aqueous layer is extracted with ethyl acetate (3 x 50 mL). The combined organic layers are dried over MgS04, filtered and concentrated to afford crude l-(2-bromo-pyridin-4-yl)-cyclopropanecarbaldehyde (ES+ m/z 226.48; 228.47), which is used without purification. | ||
To a chilled (-78C) solution of l-(2-bromopyridin-4-yl)-cyclopropanecarbonitrile (1.16 g, 5.2 mmol) in toluene (30 mL) is added a 1 M solution of diisobutylaluminum hydride (DIBAH) (10.4 mL) in toluene. The mixture stirred at -78C for 1 hour and is then warmed to room temperature. After 1 hour, EtOAc (30 mL) is added, followed by 1 M aqueous solution of H2S04 (30 mL). The organic phase is separated and the aqueous layer is extracted with EtOAc (3 x 50 mL). The combined organic layers are dried over MgS04, filtered and concentrated to afford crude l-(2-bromopyridin-4-yl)- cyclopropanecarboxaldehyde which is used without purification. MS mJz 226.5, 228.5 |