Structure of 877173-84-7
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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. : | 877173-84-7 |
Formula : | C6H3BrClN3 |
M.W : | 232.47 |
SMILES Code : | ClC1=CC=NC2=C(Br)C=NN12 |
MDL No. : | MFCD12755892 |
InChI Key : | LZWBPGVLNBNKSM-UHFFFAOYSA-N |
Pubchem ID : | 21897627 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 45.7 |
TPSA ? Topological Polar Surface Area: Calculated from |
30.19 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.83 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.98 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.15 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.95 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.8 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.94 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.13 |
Solubility | 0.171 mg/ml ; 0.000734 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.24 |
Solubility | 1.34 mg/ml ; 0.00576 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.19 |
Solubility | 0.15 mg/ml ; 0.000647 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 |
-6.31 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 |
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) |
1.86 |
* 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 |
---|---|---|
91% | With N-ethyl-N,N-diisopropylamine; In isopropyl alcohol; at 80℃; | The amine (1.1 equivalents) and 1.5 equivalents of diisopropylethylamine in isopropanol at a total concentration of 1M were heated overnight at 80 0C. The reaction mixture was concentrated, washed with water, filtered, and the resulting solid partitioned between ethyl acetate or dichloromethane and water. After a further water wash, and a citirc acid wash with amines possessing no additional basic functionality, the organic layer was dried then concentrated to give the crude 7-substituted amino-3- bromopyrazolo[1 ,5a]pyrimidine in good yield. The purity of this material was sufficient for use in the next stage cross-couipling reaction. As Example 1, the use of 2- aminomethylpyidine gave 7- aminomethyl-3-bromopyrazolo[1 ,5a]pyrimidine in 91% yield and 99% purity (MS: m/z 306/304 [M+H]+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With N-ethyl-N,N-diisopropylamine; In isopropyl alcohol; at 80℃; for 16.0h; | To a solution of 3-bromo-7-chloropyrazolo[1 ,5-a]pyrimidine (9.63 g, 41.5 mmol) and diisopropylethylamine (10.9 ml_, 62.3 mmol) in 2-propanol (42 ml_) was added 2- EPO <DP n="47"/>(aminomethyl)thiophene (5.6 g, 49.8 mmol): After heating for 16 h at 80 0C, the reaction mixture was concentrated and the residue partitioned between dichloromethane and water. After separation, the organic phase was washed with 10% citric acid and brine, dried and concentrated to yield the desired 3-bromo-7-(2- thiophenemethylamino)pyrazolo[1 ,5-a]pyrimidine (11.49 g, 92%) as a brown solid. HPLC 99%; 1H NMR (250 MHz, CDCI3) delta 8.88 (t, J = 6.4 Hz, 1H), 8.25 (s, 1H), 8.18 (d, J = 5.3 Hz, 1 H), 7.38 (dd, J = 1.3, 5.1 Hz, 1H), 7.13 (dd, J = 1.3, 3.4 Hz, 1H), 6.95 (dd, J = 3.4, 5.1 Hz, 1H), 6.29 (d, J = 5.3 Hz, 1H), 4.80 (d, J = 6.4 Hz, 2H); 13C NMR (62.9 MHz, CDCI3) delta 150.5, 146.7, 145.5, 143.1, 140.8, 126.8, 126.2, 125.4, 86.5, 81.0, 40.0; MS (APCI) 311/309 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With N-Bromosuccinimide; In dichloromethane; at 0 - 20℃; for 16.0h; | A solution of crude 7-chloropyrazolo[1,5-a]pyrimidine (44.2 g, 289 mmol) in dichloromethane (289 mL) was cooled to 0 0C using an ice bath. Lambda/-bromosuccinimide(51.4 g, 289 mmol) was added slowly to the solution that was stirred for 16 h at room temperature. The dark orange solution was diluted with dichloromethane (200 mL) and was washed with 10% potassium carbonate solution (3 x 150 mL) and brine (100 mL).The organic phase was dried and concentrated to give a dark orange solid, which was triturated using MeOH to yield the desired product, 3-bromo-7-chloropyrazolo[1,5- EPO <DP n="46"/>a]pyrimidine (50.9 g, 76%) as a yellow solid. HPLC 96%; lH NMR (250 MHz, CDCI3) delta 8.49 (d, J = 5.2 Hz, 1H), 8.25 (s, 1H), 7.07 (d, J = 5.2 Hz, 1H); 13C NMR (62.9 MHz, DMSO) delta 150.4, 145.9, 144.7, 138.5, 109.5, 84.7. |
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