Structure of 219928-13-9
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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. : | 219928-13-9 |
Formula : | C10H12BrN |
M.W : | 226.11 |
SMILES Code : | BrC1=CC(N2CCCC2)=CC=C1 |
MDL No. : | MFCD04112531 |
InChI Key : | SKCNYQBWULWGAP-UHFFFAOYSA-N |
Pubchem ID : | 7016459 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302+H312+H332-H315-H319-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.4 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 58.78 |
TPSA ? Topological Polar Surface Area: Calculated from |
3.24 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.58 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
4.25 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.67 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.07 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.02 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.12 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.22 |
Solubility | 0.0135 mg/ml ; 0.0000598 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.03 |
Solubility | 0.0211 mg/ml ; 0.0000934 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.7 |
Solubility | 0.0449 mg/ml ; 0.000199 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) |
Yes |
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 |
-4.66 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<2.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.56 |
* 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 |
---|---|---|
99% | With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene at 80℃; for 4.5 h; Sealed tube | Commercial 1,3-dibromobenzene 1 (200.0mg, 0.85mmol), 12 pyrrolidine (60.5mg, 0.85mmol) and 157.0mg of a reagent constituted by 13 tris(dibenzylideneacetone)dipalladium(0), 14 BINAP and 15 t-BuONa (mol ratio: 0.05:0.15:2) were suspended in 16 toluene (2.5mL) and allowed to react in a sealed tube, at 80°C for 4.5h, under magnetic stirring. After cooling to room temperature, the mixture was filtered under reduced pressure and the resulting solution evaporated in vacuo. The residue was dissolved in CHCl3 and washed with a 10percent aqueous solution of 60 NaOH. The organic phase was dried over anhydrous Na2SO4, filtered, evaporated in vacuo, and purified by flash column chromatography on silica gel (petroleum ether), obtaining the intermediate 2 as a transparent oil (190.5mg, 0.84mmol). Yield: 99percent. 1H NMR (CDCl3, 400MHz) δ (ppm): 7.05 (t, 1H, J=8.0Hz), 6.76–6.74 (m, 1H), 6.68 (m, 1H), 6.46 (m, 1H), 3.27–3.24 (m, 4H), 2.05–1.99 (m, 4H). |
54% | With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene for 4 h; Reflux | 1,3-Dibromobenzene (1.0 g, 4.24 mmol), pyrrolidine (0.43 mL, 5.0 mmol), sodium tert-butoxide (1.14 g, 11.87mmol) and BINAP (0.2 g, 0.32 mmol) were dissolved in 17 mL of toluene. Pd2(dba)3 (0.097 g, 0.1 mmol) was addedthereto, and the mixture was stirred 4 hours under reflux. Solids were filtered through Celite and purified by columnchromatography to obtain the title compound (0.52 g, 54percent).1H-NMR (CDCl3) δ 7.05 (1H, t), 6.75 (1H, d), 6.67 (1H, m), 6.45 (1H, m), 3.26 (4H, m), 2.00 (4H, m) |
45% | With caesium carbonate In toluene at 120℃; | Synthesis of 1-(3-bromophenyl)pyrrolidine Into a 500 mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 1,3-dibromobenzene (20 g, 84.78 mmol, 1.00 equiv) in toluene (300 mL). To this was added pyrrolidine (6.03 g, 84.80 mmol, 1.00 equiv). Addition of Pd(OAc)2 (190 mg, 0.85 mmol, 0.01 equiv) was next. This was followed by the addition of BINAP (760 mg, 2.53 mmol, 0.03 equiv). To the mixture was added Cs2CO3 (69.1 g, 211.96 mmol, 2.50 equiv). The resulting solution was allowed to react, with stirring, overnight while the temperature was maintained at 120° C. in a bath of oil. The reaction progress was monitored by TLC (EtOAc/PE=1:5). A filtration was performed. The filtrate was concentrated by evaporation under vacuum using a rotary evaporator. The residue was purified by eluding through a column with a PE solvent system. This resulted in 8.51 g (45percent) of 1-(3-bromophenyl)pyrrolidine as a light yellow liquid. LC-MS (ES, m/z): [M+H]+ calcd for C10H13BrN 226, found 226 |
45% | With caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In toluene at 120℃; | Synthesis of 1-3-bromophenyl)pyrrolidine Into a 500 mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 1,3-dibromobenzene (20 g, 84.78 mmol, 1.00 equiv) in toluene (300 mL). To this was added pyrrolidine (6.03 g, 84.80 mmol, 1.00 equiv). Addition of Pd(OAc)2 (190 mg, 0.85 mmol, 0.01 equiv) was next. This was followed by the addition of BINAP (760 mg, 2.53 mmol, 0.03 equiv). To the mixture was added Cs2CO3 (69.1 g, 211.96 mmol, 2.50 equiv). The resulting solution was allowed to react, with stirring, overnight while the temperature was maintained at 120° C. in a bath of oil. The reaction progress was monitored by TLC (EtOAc/PE=1:5). A filtration was performed. The filtrate was concentrated by evaporation under vacuum using a rotary evaporator. The residue was purified by eluding through a column with a PE solvent system. This resulted in 8.51 g (45percent) of 1-(3-bromophenyl)pyrrolidine as a light yellow liquid. LC-MS (ES, m/z): [M+H]+ calcd for C10H13BrN 226, found 226 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 7 h; | To a solution of 1-bromo-3-fluorobenzene (250 mg, 1.429 mmol) in DMF (Volume: 5 mL) was added pyrrolidine (122 mg, 1.714 mmol) followed by K2C03 (395 mg, 2.86 mmol) and heated to 100 °C for 7 h. The reaction was diluted with 50 mL DCM and 50 mL water. The organic layer was separated, washed with water (2x20 mL), dried (MgSO4) and concentrated under reduced pressure. The crude product was purified by silica gel chromatography eluting with 10-50percent ethyl acetate:hexanes to afford the desired product 62 (226 mg, 1.000 mmol, 70percent yield). 1H NMR (500 MHz, CD3OD) : 7.02 (t, J= 8.0 Hz, 1H), 6.68 (dd, J= 8.0 Hz, J= 1.0 Hz, 1H), 6.65 (t, J= 2.0 Hz, 1H), 6.48 (dd, J= 8.5 Hz, J= 2.5 Hz, 1H), 3.23 (t, J= 6.5 Hz, 4H), 2.01 (quintet, J=3.5 Hz, 4H) |
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