Structure of 633328-95-7
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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. : | 633328-95-7 |
Formula : | C5H4BrClN2 |
M.W : | 207.46 |
SMILES Code : | BrC1=CN=C(N=C1C)Cl |
MDL No. : | MFCD13193654 |
InChI Key : | IIALSLVGUGOODS-UHFFFAOYSA-N |
Pubchem ID : | 20600736 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P264-P271-P280-P302+P352-P304+P340+P312-P305+P351+P338-P332+P313-P337+P313-P403+P233-P405-P501 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.2 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 39.71 |
TPSA ? Topological Polar Surface Area: Calculated from |
25.78 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.09 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.26 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.2 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.33 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.7 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.12 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.04 |
Solubility | 0.188 mg/ml ; 0.000905 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.44 |
Solubility | 0.757 mg/ml ; 0.00365 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.51 |
Solubility | 0.0635 mg/ml ; 0.000306 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 |
-5.96 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) |
1.67 |
* 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 |
---|---|---|
80% | With triethylamine; In ethanol; at 75.0℃; for 72.0h; | STEP A: (S)-5-Bromo-4-methyl-2-(3-(methylsulfonyl)pyrrolidin-1-yl)pyrimidine [0638] A 40 mL vial was charged with 5-bromo-2-chloro-4-methylpyrimidine (348 mg, 1.675 mmol), (5)-3-(methylsulfonyl)pyrrolidine (250 mg, 1.675 mmol), and Et3N (0.701 mL, 5.03 mmol) in EtOH (90 mL). The resulting yellow solution was stirred at 75C for 3 days. The reaction mixture was partitioned between water (40 mL) and ethyl acetate (40 mL). The organic and aqueous layers were separated, and the aqueous layer was back-extracted with ethyl acetate (75 mL). The organic layers were combined, washed with brine (40 mL), dried over Na2S04, filtered, and concentrated to give the title compound as a white solid, which was used without further purification (430 mg, 80%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With tert.-butylnitrite; N-benzyl-N,N,N-triethylammonium chloride; In dichloromethane; at 25℃; for 2h; | Tert-butyl nitrite (16 g, 155 mmol) was added dropwise to a mixture of <strong>[17321-93-6]5-bromo-4-methyl-2-pyrimidinylamine</strong> (5 g, 26.59 mmol), and benzyltriethylammoniumchloride (27 g, 118.54 mmol) in dichloromethane (200 mL). The reaction mixture was stirred at 25° C. for 2 hours. The reaction mixture was diluted with H2O (50 mL), neutralized with sat. NaHCO3 and extracted with dichloromethane (300 mL×3). All of the dichloromethane layers were combined, dried over Na2SO4, filtered and evaporated. The residue was purified by silica-gel column chromatography (petroleum ether/ethyl acetate=10:1) to give 5-bromo-2-chloro-4-methyl-pyrimidine (2.5 g, 45percent yield) as a white solid. LCMS (ESI) [M+H]+=208.9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
17% | To a stirred solution of (2-methyl-[l,l*-biphenyl]-3-yl)methanol (7.1 g, 0.036 mol) in DMF (60 mL) at 0C, sodium hydride (1.73 g, 60% in minerali oil, 0.043 mol) was added and stirred at room temperature for 30 minutes. To this mixture, 5- bromo-2-chloro-4-methylpyrimidine (5 g, 0.024 mol) was added and allowed to stir at room temperature for 16h. After completion of the reaction, the reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (2 x 100 mL). The combined organic layer was then dried over sodium sulfate, filtered and evaporated to give crude product. The crude product was purified on column chromatography (silicagel, 100-200) using 10% ethyl acetate in hexane as eluent to afford 5-bromo-4- methyl-2-((2-methyl-[l, -biphenyl]-3-yl)methoxy)pyrimidine as off-white solid (Yield: 1.5 g, 17%). LCMS (ES) m/z = 369.01 [M+H]+; MR (400 MHz, CDC13): delta 2.31 (s, 3H), 2.58 (s, 3H), 5.47 (s, 2H), 7.21-7.23 (m, 2H), 7.25-7.30 (m, 2H), 7.35 (m, 1H), 7.39-7.43 (m, 2H), 7.49 (m, 1H), 8.47 (s, 1H). HPLC purity 214 nm, 99.78%. |
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