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Type | HazMat fee for 500 gram (Estimated) |
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Structure of 4399-47-7
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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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Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
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CAS No. : | 4399-47-7 |
Formula : | C4H7Br |
M.W : | 135.00 |
SMILES Code : | BrC1CCC1 |
MDL No. : | MFCD00001317 |
InChI Key : | KXVUSQIDCZRUKF-UHFFFAOYSA-N |
Pubchem ID : | 78110 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H225-H315-H319-H335 |
Precautionary Statements: | P210-P261-P305+P351+P338 |
Class: | 3 |
UN#: | 1993 |
Packing Group: | Ⅱ |
Num. heavy atoms | 5 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 27.1 |
TPSA ? Topological Polar Surface Area: Calculated from |
0.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.92 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.9 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.93 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.03 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.25 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.01 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.87 |
Solubility | 1.8 mg/ml ; 0.0134 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.52 |
Solubility | 4.05 mg/ml ; 0.03 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.58 |
Solubility | 3.57 mg/ml ; 0.0264 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
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 |
-5.77 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 |
3.0 |
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) |
3.01 |
* 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 potassium carbonate; In water; N,N-dimethyl-formamide; | a 3-Cyclobutyloxy-2-pyridinemethanol 3-Hydroxy-2-(hydroxymethyl)pyridine hydrochloride (1.57 g, 0.009 mol), potassium carbonate (8.09 g, 0.058 mol) and cyclobutyl bromide (5.0 g, 0.037 mol) were stirred together under nitrogen in N,N-dimethylformamide (20 ml) at 50 C. overnight. Water (40 ml) was added, and the resultant solution was acidified to pH 1 with hydrochloric acid (5 N). The solution was washed with dichloromethane (3*100 ml), basified to pH 14 with sodium hydroxide solution (4 N), and extracted with dichloromethane (3*100 ml). The organic layers from the extraction were combined, washed with water (1*100 ml), dried over magnesium sulfate and concentrated in uacuo to give a dark brown solid which was recrystallized from hexane to give the title compound (0.44 g). 1H NMR (250 MHz, CDCl3) δ 1.61-1.81 (1H, m), 1.86-1.91 (1H, m), 2.09-2.22 (2H, m), 2.39-2.51 (2H, m), 4.31 (1H, br s), 4.66 (1H, m), 4.74 (1H, s), 6.97 (1H, m), 7.07-7.17 (1H, m), 8.13 (1H, m); MS (ES+) m/e 180 [MH]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With potassium carbonate; In N,N-dimethyl-formamide; at 60 - 80℃; for 19.0h; | 2-Bromo-5-hydroxypyridine (1.0 g, 5.75 mmol), bromocyclobutane (0.783 mL, 8.33 mmol), and potassium carbonate (1.59 g, 11.5 mmol) were mixed in DMF (11 mL) and stirred at 60 C. for 5 h, then at 80 C. for 14 h. The reaction mixture was diluted with EtOAc and washed with water, saturated NaHCO3, and brine. The organic layer was dried (Na2SO4) and concentrated. The crude product was purified by ISCO (40 g), eluting with a gradient of EtOAc/hexane 0-10% to provide to give 2-bromo-5-cyclobutoxypyridine (0.92 g, 4.0 mmol, 70% yield) as white solid. ESI (M+1) 229.9. |
69.9% | With potassium carbonate; In hexane; N,N-dimethyl-formamide; | Step 1: Synthesis of 2-bromo-5-cyclobutoxypyridine The mixture of 2-bromo-5-hydroxypyridine (1 g, 5.75 mmol), bromocyclobutane (0.783 mL, 8.33 mmol) and potassium carbonate (1.589 g, 11.49 mmol) in DMF (11.5 mL) was stirred at 60 C. for 5 h, then at 80 C. for 14 h. The reaction mixture was diluted with EtOAc and washed with water, saturated NaHCO3, and brine. The organic layer was dried (Na2SO4) and concentrated. The crude product was purified by ISCO (40 g), eluting with a gradient of EtOAc/hexane 0-10% to provide to give 2-bromo-5-cyclobutoxypyridine (0.916 g, 4.02 mmol, 69.9% yield) as white solid. MS: M+ 228, 230. C9H10BrNO, MW=228.09 |
With potassium carbonate; In N,N-dimethyl-formamide; at 60 - 80℃; for 14.0h; | 2-bromo-5-(cyclobutyloxy)pyridine 6-Bromo-3-pyridinol (1 g, 5.75 mmol), bromocyclobutane (0.812 ml, 8.32 mmol) and potassium carbonate (1.589 g, 11.49 mmol) were mixed in N,N-dimethylformamide (11.5 ml) and were stirred at 60 C. for 5 hours then at 80 C. for 9 hours. The reaction was diluted with ethyl acetate (120 ml) and washed with water (40 ml), saturated aqueous sodium hydrogencarbonate (30 ml) and brine (30 ml). The organic phase was passed through a hydrophobic PTFE frit and evaporated. The crude was purified on silica eluding with cyclohexane/ethyl acetate: 99/1 to 9/1 to afford the title compound (820 mg), which eluted at cyclohexane/ethyl acetate: 95/5. 1H NMR (400 MHz, CDCl3): δ 7.91 (1H, d), 7.35 (1H, d), 7.02 (1H, dd), 4.64 (2H, qui), 2.39-2.53 (2H, m), 2.11-2.25 (2H, m), 1.84-1.97 (1H, m), 1.64-1.80 (1H, m); UPLC-MS: 0.78 min, 228, 230 [M+H]+; TLC: Rf=0.74 (cyclohexane/ethyl acetate: 3/1, silica). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
5.21% | 4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (300 mg, 1.55 mmol) was dissolved in DMF (5 mL) at 0 C under Ar. NaH (60% in oil, 40.8 mg, 1.70 mmol) was added portionwise, and the reaction mixture was then stirred for 20 minutes at rt. A solution of bromocyclobutane (209 mg, 1.55 mmol) in 1 mL of DMF was added, and stirring was continued 2 h at rt. The reaction mixture was quenched with saturated aq. NH4Cl, and then extracted 3x with EtOAc, washed with brine, dried with Na2SO4, filtered and concentrated. The product was purified by silica gel chromatography to provide pyrazole boronate 20A (40 mg, 5.21 %) . MS (ESI): m/z 249.0 (M+H). | |
4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (CAS 269410-08-4, 1.20 g, 6.18 mmol) was dissolved in DMF (23 mL) and sodium hydride (0.81 g, 18.6 mmol) was added at room temperature (rt). After 10 min, cyclobutyl bromide (2.51 g, 18.6 mmol) was added and the mixture stirred for 2 g at 50 C and further 16 h at rt. The mixture was partitioned between water and ethyl acetate, extracted with ethyl acetate, and the combined organic layers washed with water, dried (Na2SC>4) and concentrated. The crude product (1.14 g, 87% purity, 64% yield) was used without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
<strong>[14521-81-4]3-fluoro-1H-pyrazole</strong> (150 mg, 2.91 mmol) were dissolved in DMF (10 mL) at RT. Sodium hydride (152 mg, 3.49 mmol, 1 .2 eq) was added and the mixture stirred for 10 min. Then cyclobutylbromide (0.82 mL, 8.71 mmol, 3 eq. ) was added and the mixture stirred for 2 h at 50 C. After cooling to RT, the mixture was poured into water and extracted 4x with ethyl acetate. The combined organic layers were washed with brine, dried with sodium sulfate and the solvents removed in vacuo. The crude product afforded no further purification: 400 mg (98% of theory) pale yellow oil. 1H NMR (400 MHz, DMSO-d6) delta [ppm] 1 .68 - 1 .79 (m, 2H), 2.28 -2.43 (m, 4H), 4.88 (quint, 1 H), 5.91 (dd, 1 H), 7.71 (t, 1 H). LCMS (method 1 ): Rt = 0.84 min; MS (ESIPos) m/z = 141 (M+H) |