Structure of 652160-72-0
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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. : | 652160-72-0 |
Formula : | C5H2BrFN2O2 |
M.W : | 220.98 |
SMILES Code : | BrC1=NC=C(C=C1[N+](=O)[O-])F |
MDL No. : | MFCD05662387 |
InChI Key : | XJFDIIHIXNIWQH-UHFFFAOYSA-N |
Pubchem ID : | 20791243 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 11 |
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 | 40.72 |
TPSA ? Topological Polar Surface Area: Calculated from |
58.71 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.23 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.81 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.31 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.49 |
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 |
1.25 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.69 |
Solubility | 0.453 mg/ml ; 0.00205 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.66 |
Solubility | 0.481 mg/ml ; 0.00218 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.54 |
Solubility | 0.631 mg/ml ; 0.00286 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 |
-6.36 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 |
3.0 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) |
2.23 |
* 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 |
---|---|---|
77% | With N,N-dimethyl-formamide; phosphorus(V) oxybromide; at 20 - 110℃; for 3.08333h; | A total of 117 g of 5-80 was divided in 4 batches of 30 g×3 and 27 g×1 and treated with POBr3 (3 equiv.; 163 g×3 and 155 g×1) and a catalytic amount of DMF (15 ml) at rt (DMF was added carefully gas evolution). After 5 min. at room temperature, the solutions were heated at 110 C. for 3 hr. LC/MS showed starting material had been consumed. The reaction mixtures were allowed to cool to rt. The reaction flasks were placed in an ice bath; and then ice was added very slowly and carefully portionwise into the flask, gas evolution was due to HBr formation; the liquid and black solid that formed was poured into a beaker with ice. EtOAc was added and the mixture was then extracted several times with EtOAc. The organic layer was washed with saturated aq. NaHCO3; H2O and brine; dried over Na2SO4 and filtered. The product was dried in the pump overnight to provide 123 g of 6-80 as a brown solid (77% yield). [1498] Note: Reaction is completed within 1 h. [1499] 1HNMR(delta, CDCl3):8.52 (m, 1H), 7.93 (m, 1H). |
77 - 97% | With phosphorus(V) oxybromide;N,N-dimethyl-formamide; at 20 - 110℃; for 3h; | A total of 117 g of intermediate 4 was divided in 4 batches of 30 g×3 and 27 g×1 and treated with POBr3 (3 equiv.; 163 g×3 and 155 g×1) and a catalytic amount of DMF (15 ml) at rt (DMF was added carefullygas evolution). After 5 min. at room temperature, the solutions were heated at 110 C. for 3 hr. LC/MS showed starting material had been consumed. The reaction mixtures were allowed to cool to rt. The reaction flasks were placed in an ice bath; and then ice was added very slowly and carefully portionwise into the flask, gas evolution was due to HBr formation; the liquid and black solid that formed was poured into a beaker with ice. EtOAc was added and the mixture was then extracted several times with EtOAc. The organic layer was washed with saturated aq. NaHCO3; H2O and brine; dried over Na2SO4 and filtered. The product was dried in the pump overnight to provide 123 g of intermediate 5 as a brown solid (77% yield). Note: Reaction is completed within 1 h. 1HNMR(delta, CDCl3):8.52 (m, 1H), 7.93 (m, 1H). |
77% | With phosphorus(V) oxybromide;N,N-dimethyl-formamide; at 110℃; for 3h; | A total of 117 g of 5-80 was divided in 4 batches of 30 g×3 and 27 g×1 and treated with POBr3 (3 equiv.; 163 g×3 and 155 g×1) and a catalytic amount of DMF (15 ml) at rt (DMF was added carefully gas evolution). After 5 min. at room temperature, the solutions were heated at 110 C. for 3 hr. LC/MS showed starting material had been consumed. The reaction mixtures were allowed to cool to rt. The reaction flasks were placed in an ice bath; and then ice was added very slowly and carefully portionwise into the flask, gas evolution was due to HBr formation; the liquid and black solid that formed was poured into a beaker with ice. EtOAc was added and the mixture was then extracted several times with EtOAc. The organic layer was washed with saturated aq. NaHCO3; H2O and brine; dried over Na2SO4 and filtered. The product was dried in the pump overnight to provide 123 g of 6-80 as a brown solid (77% yield). Note: Reaction is completed within 1 h. 1HNMR(delta, CDCl3):8.52 (m, 1H), 7.93 (m, 1H). |
With phosphorus(V) oxybromide; In DMF (N,N-dimethyl-formamide); at 110℃; | Intermediate 4,4-fluoro-7-bromo-6-azaindole, was prepared according to the following scheme: [CHEMMOL-00081] [0364] A) fuming HNO3, H2SO4; [0365] B) POBr3/DMF, 110 C.; [0366] C) vinylmagnesium bromide, THF, -78 C. -20 C. [0367] Intermediate 4 was isolated as a brownish solid. MS m/z: (M+H)+ calcd for C7H5BrFN2: 214.96; found 214.97. HPLC retention time: 1.28 minutes (column G). |
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